Sunday, June 29, 2008

The Fundamentals of Multiple Sclerosis Care

The Fundamentals of Multiple Sclerosis Care
HealthCentral.com Sun, 29 Jun 2008 7:06 AM PDT
There is a lot of talk about research and medical advances in the treatment of multiple sclerosis , but I would like to return to the fundamentals of MS care and how ...
The Fundamentals of Multiple Sclerosis Care
HealthCentral.com Sat, 28 Jun 2008 6:21 AM PDT
There is a lot of talk about research and medical advances in the treatment of multiple sclerosis , but I would like to return to the fundamentals of MS care and how these new treatment options fall into the framework of MS care.



MS Patients at Higher Risk for Restless Legs Syndrome
HealthDay via Yahoo! News Fri, 27 Jun 2008 11:02 AM PDT
FRIDAY, June 27 (HealthDay News) -- People with multiple sclerosis are at a greater risk than the general population for developing restless legs syndrome (RLS), a new Italian study suggests.
MS Patients at Higher Risk for Restless Legs Syndrome
KOLD News 13 Tuscon Fri, 27 Jun 2008 2:45 PM PDT
By Alan Mozes , HealthDay Reporter FRIDAY, June 27 (HealthDay News) -- People with multiple sclerosis are at a greater risk than the general population for...

More research suggests that vitamin D is important to overall health
Orlando Sentinel - Orlando,FL,USA
The so-called Sunshine Vitamin may play an important role in overall health, according to a new study that links higher vitamin D levels with lower death ...
See all stories on this topic
Organization helps people who can't afford their prescriptions
KSL-TV - Salt Lake City,UT,USA
Williams' battle with multiple sclerosis inspired him to team up with a coalition of pharmaceutical companies to provide free or nearly free medication for ...
See all stories on this topic

Multiple Sclerosis Treatment: The Fundamentals
HealthCentral.com - Arlington,VA,USA
Most of the research you read about is aimed at disease modification: the oral medications (Cladribine, Fingolimod, Teriflunomide, BG00012, Laquinomod, etc. ...
See all stories on this topic
Second MS Para Dressage Rider Confirmed For Beijing, UK
A second top Para Dressage rider has been chosen for the fourth time to join team GB at the 2008 Paralympics in Beijing. Anne Dunham will join training mate Simon Laurens - who featured in this month's MS Matters - on the trip in September and is hoping for an individual as well as team gold medal.

Yale Researchers Find Molecule That Guides Migrating Axons
The human nervous system is like a giant home entertainment system, but instead of 20-odd wires there are trillions of connections that must be made perfectly before the network operates effectively.
New Brain Treatments Possible After Stem Cell Breakthrough
MedIndia - Chennai,India
Lipton and his team found a solution to this problem by inducing ES cells to express a protein, discovered in his laboratory called myocyte enhancer factor ...
See all stories on this topic
Mending a broken mind
Globe and Mail - Canada
Research suggests it may have an impact on the very structure of the brain. In the mid-nineties, University of Calgary cell biologist Samuel Weiss ...
See all stories on this topic

Friday, June 27, 2008

Scientists repair brain using GM embryo cells

Scientists repair brain using GM embryo cells
Telegraph.co.uk - United Kingdom
Scientists at the Burnham Institute for Medical Research in La Jolla, California, have, for the first time, genetically programmed embryonic stem cells, ...
See all stories on this topic


Author : Partnership for Prescription Assistance
Earthtimes (press release) - London,UK
The occasion was marked by a visit to Salt Lake City by the program's national spokesman, TV talk-show host Montel Williams . Hall, a 27-year-old college ...
See all stories on this topic

Potential Safer, More Effective Gene Therapy
The potential of gene therapy has long been hampered by the risks associated with using viruses as vectors to deliver healthy genes, but a new University of Georgia study helps bring scientists closer to a safe and efficient gene delivery method that doesn't involve viruses.


Caregivers / Homecare News

Stepfamilies Make Caring More Complex In Late-Life Remarriage
"I felt so insulted and so hurt. It was like [their father] had met some gal at a bar and married her the next day, and she wanted all his money. I felt they didn't give me any credit, or any respect, appreciation or anything.


Trading Ideas: Teva Pharma
istockAnalyst.com - Salem,OR,USA
Teva’s principal products include Copaxone for multiple sclerosis; and Azilect for Parkinson’s disease. The stock has been holding in there these days as it ...
See all stories on this topic

Elan so high it may soon succumb to profit-taking
Irish Independent - Dublin,Ireland
The stock had already been racing ahead in recent months on evidence that patient take-up of Tysabri, co-developed with Biogen Idec, has been growing ...
See all stories on this topic


This is livin'
Colorado Springs Independent - Colorado Springs,CO,USA
Anyway, Lane and his wife moved to Trinidad in 1994, where he lived another three years before losing his battle with multiple sclerosis. ...
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In Vivo Detection of Apoptosis
RedOrbit - Dallas,TX,USA
The imaging of inflammation-associated apoptosis, particularly chronic inflammation (such as that seen in Alzheimer's disease, multiple sclerosis, ...
See all stories on this topic


PET Imaging of Cancer Immunotherapy
RedOrbit - Dallas,TX,USA
In experimental autoimmune encephalitis, a murine model of multiple sclerosis. INF-FDG enabled visualization of spinal cord inflammation through activated ...
See all stories on this topic

The image “http://www.msanswers.ca/App_Themes/AskTheExpert_English/Images/headerEN.gif” cannot be displayed, because it contains errors. Treatment

Treatment

Dr. Freedman

Professor of medicine in the field of neurology at the University of Ottawa, ON
View BIO

Q :
My brother was diagnosed with MS 10 years ago and he is getting worst, he started using a cane a month ago and now he needs a walker, the doctor is suggesting Chemotherapy as a treatment. I am wondering how effective Chemotherapy is for MS.
A :
This is a very complicated issue in the sense that not all progression is the same. In the belief that continued inflammation gone unchecked eventually wears down the nervous system’s ability to either compensate for loss or to fend off further damage, chemotherapy treatment may do something to finally end the inflammatory attack. This will not result in any improvements per se, but more likely a stabilization of the progression. On the other hand, if progression is the result of cumulative inflammatory attacks over many years and the end result is a nervous system that is worn down and no longer can compensate for the total losses, then it’s unlikely chemotherapy will help, since the inflammation is long gone.
6/27/2008 1:08:09 PM
More answers from Dr. Mark Freedman
More answers in the category: Treatment

 

http://www.msanswers.ca/QuestionView.aspx?L=2&QID=1935


The image “http://www.msanswers.ca/App_Themes/AskTheExpert_English/Images/headerEN.gif” cannot be displayed, because it contains errors. Symptoms and Management

Symptoms and Management

Dr. Myles

Associate Clinical Professor of Neurology at the University of Alberta
View BIO

Q :
In Jan. 2007, at age 63, I was diagnosed with Primary Progressive MS. I am currently taking 3200 mg of the drug Gabapentin daily. It seems to have helped with regard to the spasticity, but the overall pain is often more than I can bare, especially in the neck and shoulders. I'm OK when horizontal, but really suffer when sitting or standing even after just a few minutes. Is there anything that will help relieve this pain?
A :
The type of pain that you describe, which occurs in a “coat hanger” distribution when sitting/standing, but not when horizontal, can be a sign of something called orthostatic hypotension, which is a fall in blood pressure that occurs when one is in an upright posture (sitting/standing). It can occur in neurological conditions that affect autonomic function (resulting in impaired blood pressure regulation), including some neurodegenerative diseases, spinal cord injury and others. It is very important to get this assessed. If this is what is causing your pain, there are specific treatments that might help, whereas painkillers probably won’t help much at all.
6/27/2008 1:11:03 PM
More answers from Dr. Mary Lou Myles
More answers in the category: Symptoms and Management

 

http://www.msanswers.ca/QuestionView.aspx?L=2&QID=1910


Score with MS fundraiser
Independent and Free Press - Georgetown,ON,Canada
He is also one of thousands in Ontario living with multiple sclerosis (MS). Diagnosed at age 33, Stewart told doctors he “didn’t have time for MS. ...
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Peter takes to the skies
Eastbourne Today - Eastbourne,England,UK
Seaford resident Peter Dawson, who also suffers from Multiple Sclerosis, decided to do the skydive at Headcorn airfield in Kent last Saturday after being ...
See all stories on this topic

Media Advisory - Bell Canada employees and retirees present ...
Canada NewsWire (press release) - Toronto,Ontario,Canada
... Kids Help Phone - Kingdom Covenant Community Services - Lupus Ontario - Multiple Sclerosis Scientific Research Foundation - Multiple Sclerosis Society ...
See all stories on this topic

MCG hosts Exploring MS
Lincolnton Journal - GA,USA
Multiple sclerosis is a disease that affects the brain, nerves, and spinal cord of approximately 350000 Americans in their twenties and thirties. ...
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Battling ticks and the illness they bring
WRAL.com - Raleigh,NC,USA
Tierney said he was diagnosed with Multiple Sclerosis more than two years ago because his symptoms at the time seemed to match the disease. ...
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Local group working to fight Multiple Sclerosis
Chetek Alert - WI, United States
Multiple Sclerosis is an autoimmune disease in which the body's own defense system attacks myelin, which is the protective coating on the nerves. ...
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Big Pharma pulls out of U.K. trials

There's more bad news today for the U.K.'s drug development industry. Pfizer, Roche and Merck Serono have all decided to cut back on clinical research there, according to the Financial Times. The problem, companies say, is that too few U.K. patients are receiving cutting-edge drugs like Avasin and Erbitux, making it difficult for experimental therapies to be tested against patients already on those drugs. Just yesterday the U.K.'s National Institute for Clinical Health and Excellence advised against the use of Avastin and Erbitux.

The Association of the British Pharmaceutical Industry recently found that 20 trials at just four companies didn't happen because of difficulty recruiting patients. If drug companies continue cutting back on U.K. clinical trials it could have a negative impact on drug industry. "In the long-term there is a serious risk that if we get to the point where none of the new drugs are being used in the U.K., the trials won't be done here," said Harpal Kumar, head of Cancer Research UK.

- read the Financial Times article

Wednesday, June 25, 2008

Nerve Cells Derived From Stem Cells And Transplanted Into Mice May Lead To Improved Brain Treatments

ScienceDaily (June 24, 2008) — Scientists at the Burnham Institute for Medical Research have, for the first time, genetically programmed embryonic stem (ES) cells to become nerve cells when transplanted into the brain, according to a new study published in The Journal of Neuroscience.

The research, an important step toward developing new treatments for stroke, Alzheimer's, Parkinson's and other neurological conditions showed that mice afflicted by stroke showed tangible therapeutic improvement following transplantation of these cells. None of the mice formed tumors, which had been a major setback in prior attempts at stem cell transplantation.

The team was led by Stuart A. Lipton, M.D., Ph.D., professor and director of the Del E. Webb Neuroscience, Aging, and Stem Cell Research Center at Burnham. Dr. Lipton is also a clinical neurologist who treats patients with these disorders. Collaborators included investigators from The Scripps Research Institute.

"We found that we could create new nerve cells from stem cells, transplant them effectively and make a positive difference in the behavior of the mice," said Dr. Lipton. "These findings could potentially lead to new treatments for stroke and neurodegenerative diseases such as Parkinson's disease."

Conditions such as stroke, Alzheimer's, Parkinson's and Huntington's disease destroy brain cells, causing speech and memory loss and other debilitating consequences. In theory, transplanting neuronal brain cells could restore at least some brain function, just as heart transplants restore blood flow.

Prior to this research, creating pure neuronal cells from ES cells had been problematic as the cells did not always differentiate into neurons. Sometimes they became glial cells, which lack many of the neurons' desirable properties. Even when the neuronal cells were created successfully, they often died in the brain following transplant--a process called programmed cell death or apoptosis. In addition, the cells would sometimes become tumors.

Dr. Lipton solved these problems by inducing ES cells to express a protein, discovered in his laboratory called myocyte enhancer factor 2C (MEF2C). MEF2C is a transcription factor that turns on specific genes which then drive stem cells to become nerve cells. Using MEF2C, the researchers created colonies of pure neuronal progenitor cells, a stage of development that occurs before becoming a nerve cell, with no tumors. These cells were then transplanted into the brain and later became adult nerve cells. MEF2C also protected the cells from apoptosis once inside the brain.

"To move forward with stem cell-based therapies, we need to have a reliable source of nerve cells that can be easily grown, differentiate in the way that we want them to and remain viable after transplantation," said Dr. Lipton. "MEF2C helps this process first by turning on the genes that, when expressed, make stem cells into nerve cells. It then turns on other genes that keep those new nerve cells from dying. As a result, we were able to produce neuronal progenitor cells that differentiate into a virtually pure population of neurons and survive inside the brain."

The next step was to determine whether the transplanted neural progenitor cells became nerve cells that integrated into the existing network of nerve cells in the brain. Performing intricate electrical studies, Dr. Lipton's investigative team showed that the new nerve cells, derived from the stem cells, could send and receive proper electrical signals to the rest of the brain.

They then determined if the new cells could provide cognitive benefits to the stroke-afflicted mice. The team executed a battery of neurobehavioral tests and found that the mice that received the transplants showed significant behavioral improvements, although their performance did not reach that of the non-stroke control mice. These results suggest that MEF2C expression in the transplanted cells was a significant factor in reducing the stroke-induced deficits.

The work was supported in part by National Institutes of Health (NIH) grants and a Senior Scholar Award in Aging Research from the Ellison Medical Foundation.


Adapted from materials provided by Burnham Institute.
APA

MLA
Burnham Institute (2008, June 24). Nerve Cells Derived From Stem Cells And Transplanted Into Mice May Lead To Improved Brain Treatments. ScienceDaily. Retrieved June 25, 2008, from http://www.sciencedaily.com­ /releases/2008/06/080624174843.htm#

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Tuesday, June 24, 2008

Hopkins reports success with MS treatment -- baltimoresun.com

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http://www.baltimoresun.com/news/health/bal-ms0623,0,3749061.story
baltimoresun.com
From Tuesday's Sun

Hopkins reports success with MS treatment


By Euna Lhee

Sun reporter

8:46 PM EDT, June 23, 2008

On a typical weekday, Richard Bauer jogs 2½ miles near his White Marsh home and then drives to Baltimore, where he is a first-year radiography student.

After a full day of lectures, he likes to relax by reading Japanese Performance and Motorcyclist.

"But free time is rare," he says with a grin.

Life wasn't always this way for Bauer. In recent years, he couldn't muster the strength to get out of bed. In 2004, he was diagnosed with an aggressive form of multiple sclerosis (MS), which left him paralyzed and confined to a wheelchair for more than a year.

Then Bauer tried an experimental drug regimen, and his body reacted in a manner that surprised everyone: the debilitating symptoms of MS almost disappeared.

Writing this month in a medical journal, Johns Hopkins researchers reported unexpected success in the treatment of Bauer and other MS patients who received a high dose of an immuno-suppressant drug known as cyclophosphamide.

According to the small, pilot-stage study, the regimen may not only slow the progression of MS, but also restore neurological function lost to the disease.

In the Hopkins trial, nine people, most of whom had failed to respond to other treatments, received a single infusion of cyclophosphamide over four days and then were followed for two years.

Magnetic Resonance Imaging (MRI) showed that the number of brain lesions decreased in seven of the nine volunteers, which meant that neurological function was being restored. Some began walking, controlling their bowels and bladders and returning to work for the first time in years.

"We took the worst of the worst patients. We didn't expect such a dramatic improvement in function," said Dr. Douglas Kerr, associate professor of neurology at the School of Medicine, whose report was published in the June issue of the Archives of Neurology. "There's a real need for this type of therapy for MS patients, many in the prime of their lives."

The results -- though preliminary -- offer hope for the 400,000 Americans afflicted with MS, a degenerative disease in which the immune system attacks the central nervous system. MS can cause poor coordination, blindness, paralysis and cognitive problems. The disease is not considered fatal, but it may considerably impair quality of life as symptoms come and go -- or in many cases, become permanent.

Dr. John Richert, executive vice president for research and clinical program at the National Multiple Sclerosis Society, called the results promising. He said the Hopkins scientists' methods were reasonable for a preliminary, short-term study, and said he hopes to see phase II trials in the near future to further determine the safety and efficacy of the treatment.

For Bauer, the experimental treatment meant another chance at life. As a student at the Johns Hopkins School of Medicine, he now spends eight hours a day learning about medical imaging and taking courses on CPR and medical ethics.

"I was falling apart. I was trapped in my own body," said Bauer, now 30. "I'm a regular person again. I've gotten my life back."

There are a variety of treatments approved by the Food and Drug Administration than can lessen the frequency and severity of MS attacks, but no cure.

Traditionally, doctors have administered cyclophosphamide in small, frequent doses to treat immune disorders, including MS, lupus and aplastic anemia. This method, however, can cause the drug to build up to toxic concentrations in patients' bodies and cause a variety of unpleasant side effects such as hair loss, bone marrow failure and secondary cancers.

Instead of giving patients these "pulsed" doses, Kerr administered a single dose of cyclophosphamide at a concentration several times higher than a pulsed regimen provides, but with a lower total dose than patients typically receive over time.

This so-called HiCy treatment kills off most of the patient's immune cells in one swipe and prompts the system to "reboot," giving nerve cells a fresh start.

"The concept is that the immune system has gone bad. In our approach, the dose would spare the bone marrow and allow it to create a new immune system," Kerr said. "We had hoped that we could halt the progression of the disease completely, but what we got was even better."

Kerr's colleague added that no one had ever produced a study that showed both a decrease in disability and MRI lesions. "The important thing to know now is that this is not a cure for MS. But this is the kind of treatment that can one day lead to a cure," said Dr. Adam Kaplin, assistant professor of psychiatry and neurology at the School of Medicine.

Side effects of the therapy included nausea and hair loss both which were temporary. There was also a risk of infection, which could be severe, during the week when the volunteers' immune systems shut down.

"Even if the side effects were 10 times worse, I would do it over again to be where I am today," said Bauer.

Kerr also cautioned that the "reboot" phenomenon did not occur in all the patients. And MRIs showed that the disease had reactivated in about half the study participants two years after treatment, suggesting that their renewed physical capabilities may not be permanent.

Since immune cells that reform after HiCy treatment may contain the same defect that led to MS in the first place, Kaplin is also looking for ways to regrow only healthy immune cells after the system is "rebooted."

In addition, the symptoms of two patients initially worsened after the treatment. One of them was Robert McCready, 51, of Alexandria, Va.

After conventional therapies failed, McCready underwent HiCy treatment in February 2004, and ten months later, he was admitted into the hospital after his condition deteriorated.

"I thought, 'What had we done?'" said his wife, Sheila.

But a year later, the attacks began to stabilize, and McCready was able to accompany his wife on road trips to Texas and New Jersey -- something he had been unable to do for the past decade.

"I can't give HiCy justice in describing what it has done for me" he said. "If I didn't have HiCy, I'm sure my enjoyment and reality would all have been greatly diminished."

Kaplin said that the treatment may not have worked as well on McCready as some others because he had been disabled for too long. "The damage had been done, and the nervous system couldn't have been repaired," the doctor said.

The ideal candidates for the HiCy drug regimen seem to be in the early stages of aggressive forms of MS. But researchers won't know for sure until they broaden their testing.

Researchers hope that the next trial will overcome the current study's limitations: a small number of enrolled patients, an open label (patients knew what treatment they were receiving), and no control group.

"We need this information before gaining widespread acceptance," Kerr said, referring to the multiple, double-blind, randomized trials that scientists call the gold standard for medical research.

According to the MS Society's Richert, this may not be easy to come by, given the economics of drug research. "The challenge now for the Hopkins researchers is to find a corporate sponsor, who would be willing to invest in more clinical trials," Richert said, "especially since cyclophosphamide isn't a new drug."

euna.lhee@baltsun.com

Copyright © 2008, The Baltimore Sun

http://www.baltimoresun.com/news/health/bal-ms0623,0,3749061.story

http://www.baltimoresun.com/news/health/bal-ms0623,0,3749061.story

MS News

 

Summaries of MS news from websites around the world.

2007 Stem Cell Research Summit: report now available

The report from 2007’s Stem Cell Research Summit has now been published in a peer-reviewed journal, Multiple Sclerosis. We co-funded and co-hosted the summit with the US National MS Society (NMSS) in San Francisco.

read more


Hopkins reports success with MS treatment
Baltimore Sun - United States
In 2004, he was diagnosed with an aggressive form of multiple sclerosis (MS), which left him paralyzed and confined to a wheelchair for more than a year. ...
See all stories on this topic


Chancellor presents Honorary Degrees
Cambridge Network - Cambridge,UK
He is particularly noted for the development of CAMPATH-1H, a monoclonal antibody used in the treatment of chronic lymphocytic leukaemia. ...
See all stories on this topic

She needs health insurance
San Bernardino Sun - San Bernardino,CA,USA
Specifically, Keppra is from UCB, Carbatrol ER is from Shire US, and Felbatol is from Meda Pharmaceuticals. Perhaps this is the basis from which to start. ...
See all stories on this topic

Study: Pill Slows Effects of Multiple Sclerosis
FOXNews - USA
The pill laquinimod appears to slow the disease and is well-tolerated by patients with the relapsing form of the disease, Reuters reports. ...
See all stories on this topic


Acorda shares fall on downgrade
Business in the Burbs - White Plains,NY,USA
The company has reported positive results from a study of its fampridine-SR, a treatment to help MS patients with walking. Friedman Billings lowered its ...
See all stories on this topic

Health Winners & Losers: Barrier Therapeutics
TheStreet.com - USA
... noting the lack of catalysts for the stock until early 2009, when it will seek FDA approval for its multiple sclerosis drug Fampridine-SR.
See all stories on this topic

Ahead of the Bell: Acorda Therapeutics downgraded
Forbes - NY,USA
Acorda Therapeutics Inc. plans to submit an approval application for Fampridine-SR with the Food and Drug Administration in the first quarter of 2009. ...
See all stories on this topic

Acorda Therapeutics falls following downgrade
Forbes - NY,USA
Acorda Therapeutics Inc. plans to submit an approval application for Fampridine-SR with the Food and Drug Administration in the first quarter of 2009. ...
See all stories on this topic

Premarket roundup: Acorda, Motorola
Forbes - NY,USA
AP 06.23.08, 10:29 AM ET NEW YORK (AP) - A Friedman Billings Ramsey analyst thinks shares of Acorda Therapeutics will stay around their current price until ...
See all stories on this topic


Artist creates transcendent world of color, light
The Oregonian - OregonLive.com - Portland,OR,USA
Dailey was diagnosed with multiple sclerosis in the 1970s. The disease forced the artist to move from oils to acrylic because the thinning agent used for ...
See all stories on this topic


Effectiveness of Rehabilitation Intervention in persons with Multiple sclerosis: A Randomized Controlled Trial.

The authors investigated the effectiveness of rehabilitation in people with MS. They found that it can help to reduce disability, but its impact on quality of life needs further evaluation.

authors: Khan F, Pallant JF, Brand C, Kilpatrick TJ.

source: J Neurol Neurosurg Psychiatry. 2008 Jun 5. [Epub ahead of print]

read

Clinical and radiographic spectrum of pathologically confirmed tumefactive multiple sclerosis.

The authors investigated the characteristics of a rare type of MS lesion which can cause diagnostic difficulty. They found that they were not associated with any particular disease pattern.

authors: Lucchinetti CF, Gavrilova RH, Metz I, Parisi JE, Scheithauer BW, Weigand S, Thomsen K, Mandrekar J, Altintas A, Erickson BJ, König F, Giannini C, Lassmann H, Linbo L, Pittock SJ, Brück W.

source: Brain. 2008 Jun 5. [Epub ahead of print]

read more

A first stage genome-wide screen for regions shared identical-by-descent in Hutterite families with multiple sclerosis.

The authors investigated MS genetics in a Canadian community with a tradition of marriages to blood relations. They found some genetic differences between people with and without MS, but further studies are needed.

authors: Dyment DA, Cader MZ, Datta A, Broxholme SJ, Cherny SS, Willer CJ, Ramagopalan S, Herrera BM, Orton S, Chao M, Sadovnick AD, Hader M, Hader W, Ebers GC.

source: Am J Med Genet B Neuropsychiatr Genet. 2008 Jun 5;147B(4):467-72.

read more

Involvement of the choroid plexus in multiple sclerosis autoimmune inflammation: A neuropathological study.

The authors looked at the choroid plexus, which produces spinal fluid. They found more inflammation there in people with MS which may suggest that it is involved in the condition.

authors: Vercellino M, Votta B, Condello C, Piacentino C, Romagnolo A, Merola A, Capello E, Mancardi GL, Mutani R, Giordana MT, Cavalla P.

source: J Neuroimmunol. 2008 Jun 6. [Epub ahead of print]

read more

Early identification of interferon-beta responders by ex vivo testing in patients with multiple sclerosis.

The authors investigated the role of some inflammatory molecules in the blood as predictive markers for response to interferon-beta treatment in people with MS. They found that one of them called IL-10 maybe useful in predicting response.

authors: Wiesemann E, Deb M, Hemmer B, Radeke HH, Windhagen A

source: Clin Immunol. 2008 Jun 6. [Epub ahead of print]

read mo

vitamin D

Study finds that healthy Indian hospital workers display low ...
By Amy Proal
In fact, in their introduction to a recent study on vitamin D, the team postulated further, stating that “it has been presumed that Indians have ’sufficient’ levels of vitamin D.” And who wouldn’t presume such a thing? ...
Bacteriality -- Understanding... - http://bacteriality.com

Sunlight and vitamin D good for chronic fatigue syndrome?
O the protocol patients must avoid sunlight exposure and dietary sources of vitamin D as disruption of the metabolism of this vitamin is said to be at the heart of the immune dysfunction associated with the condition.
Digg / upcoming - http://digg.com/

Vitamin D Deficit May Boost Men's Heart Attack Risk
By Ultimate Exposure(Ultimate Exposure)
Men with a vitamin D deficiency at the start of the study were more than twice as likely to have a heart attack as those in the normal range, even after other reasons such as family history, weight, diabetes and cholesterol levels were ...
Ultimate Exposure's Dose of D - http://sunbedsandvitamind.blogspot.com/

Get a little sun this summer!
By esun
Studies increasingly are suggesting the value of vitamin D – often known as the sunshine vitamin, because that’s one way you can obtain it – in everything from bone metabolism to maintaining muscle strength, immune function, ...
TanToday - Helping Salon Owners,... - http://www.tantoday.com/forums

Vitamin D May Promote Colon Cancer Survival
By Steven Reinberg, HealthDay Reporter THURSDAY, June 19 (HealthDay News) -- Colon cancer patients with high blood levels of vitamin D...
KVOA - Health - http://www.kvoa.com/global/category.asp?c=43474

Monday, June 23, 2008

Future of treatment for MS is biologic

Future of treatment for MS is biologic
Daytona Beach News-Journal - Daytona Beach,FL,USA
YONG H. TSAI Multiple sclerosis is an autoimmune disease of the central nervous system.
It occurs when immune cells, designed to protect us from infection ...
See all stories on this topic

MS Society Announces Media Award Winners, Canada
Medical News Today (press release) - UK
The Multiple Sclerosis Society of Canada announced the winners of its annual John Alexander Media Awards, recognizing excellence in print and broadcast ...
See all stories on this topic

Teva's Multiple Sclerosis Drug Slows The Disease
eMaxHealth.com - Hickory,NC,USA
Teva Pharmaceutical Industries' new drug laquinimod for multiple sclerosis slows the disease in patients with relapsing form. Multiple sclerosis (MS) is a ...
See all stories on this topic


Diagnosis and Types of MS

Dr. Short

Medical Chair Neurorehabilitation Program QEII Health Sciences Centre


View BIO

Q :
Two months ago I woke up one morning with my entire left side numb (like it was asleep) and extreme muscle stiffness. The initial diagnosis was "a virus" and I was sent home. It slowly disappeared and each day I felt a bit better until it was nearly gone. Then two weeks after the initial attack it came back again, only worse this time. I went to a different doctor who immediately sent me for blood work and put me on track for an MRI. I have just received the results of my MRI and altogether there are at least 13 lesions in my brain. I have been referred to a MS and am waiting for them to contact me.
My question is that although I have lesions in my brain, my relapsing episodes only happened two weeks apart. Will I have to wait until I have another episode to be "officially" diagnosed with MS?
A :
The answer here is no you do not have to wait for another relapse to be diagnoses with MS. There are a number of factors that go into the diagnosis of MS and the history of relapses are just one. Your MS specialists will use certain criteria to determine if you have MS or not. Your clinical story along with the MRI findings and physical exam findings by the MS doctor you are going to see should be enough to tell you whether or not you have MS without having to wait for another relapse.
6/23/2008 11:23:02 AM
More answers from Dr. Christine Short
More answers in the category: Diagnosis and Types of MS
DISCLAIMER: Please be aware that this information does not necessarily represent the opinion of the MS Society of Canada, and is not intended as medical advice. For specific advice and opinion, always consult a physician.
© 2008 Multiple Sclerosis Society of Canada | www.mssociety.ca
http://www.msanswers.ca/QuestionView.aspx?L=2&QID=1660


Vitamin D is in the news -- and it's all good
Toronto Sun - Ontario, Canada
By FRAN BERKOFF Well, here's food for thought: Recent new studies are giving more good reasons for us to get ample vitamin D, enjoy a glass of wine, ...
See all stories on this topic

Julie Deardorff |
Chicago Tribune - United States
A lack of sunlight, which leads to low vitamin D levels, could be another factor. Sunlight stimulates the production of vitamin D, which fetuses need for ...
See all stories on this topic

Suffering from pain? Pop vitamin D
Times of India - India
For people suffering from chronic pain, an extra dose of vitamin D may offer a better treatment option, according to a new research report. ...
See all stories on this topic



Riders find hope on the road
Vernon Morning Star - BC, Canada
The research they are supporting was done by McMaster University team led by Dr. Michel Rathbone and Dr. Schucui Jiang, who successfully regenerated the ...
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Thursday, June 19, 2008

Merck KGaA division collaborates on MS treatments

Merck KGaA division collaborates on MS treatments
Hays Pharma - London,Greater London,UK
Merck Serono, a Merck KGaA division, has announced that it is teaming up with Bionomics to work on new treatments for multiple sclerosis (MS). ...
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Band Against MS Awards Research Scholarship
antiMUSIC.com - CA,USA
The scholarship, issued through The Foundation of the Consortium of Multiple Sclerosis Centers (FCMSC), was awarded to UT Houston Medical School student, ...
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Lemonade stand in Belk to help MS clients, research
Charleston Post Courier - Charleston,SC,USA
Wolff's son, Justin Harl, is one of more than 500000 people nationwide who live with multiple sclerosis. Her stand is part of a special fundraising program ...
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Edwards golf tourney raises money for multiple sclerosis
Vail Daily News - Vail,CO,USA
Proceeds from the June 9 event will fund the Edwards-based Heuga Center for Multiple Sclerosis’ health and wellness programs that are designed to help ...
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MS Society looks to double their biking numbers for their 2008 MS ...
MediaSyndicate (press release) - USA
Melville, NY, 2008 - The National Multiple Sclerosis Society, Long Island Chapter set an aggressive goal of doubling their biker participation for this ...
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MS Society to fund physiotherapists
Barchester Healthcare - London,UK
The Multiple Sclerosis (MS) Society has announced plans to fund a number of specialist MS physiotherapist posts across the UK. The Multiple Sclerosis (MS) ...
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Wife's website manages illness
Auckland stuff.co.nz - Auckland,New Zealand
By HAYDEN DONNELL - North Shore Times | Thursday, 19 June 2008 NEW MESSAGE: The effect of multiple sclerosis on Tim Preston's memory inspired his wife ...
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Icahn Nominee to Biogen Idec Board Pledges to Work With Current ...
Xconomy - Cambridge,MA,USA
... partnership and Biogen’s partnership with Elan Pharmaceuticals on the multiple sclerosis and Crohn’s disease drug Tysabri could be strengthened. ...
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Merck Serono signs licensing agreement with Bionomics on multiple ...
Forbes - NY,USA
GENEVA (Thomson Financial) - Merck KGaA's unit Merck Serono said it signed a development and licensing agreement with Bionomics Ltd., under which Merck ...
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Teva's new blockbuster drug?
Globes - Rishon Le-Zion,Israel
Clal Finance Batucha analyst Gal Reiter says that Teva now has a second original drug alongside Copaxone. "If we previously estimated Azilect sales at $300 ...
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Monday, June 16, 2008

Better feel: Shannon, with her daughter, having partly recovered from paraplegia after treatment by Delhi's Dr Geeta Shroff
CONTROVERSY: STEM CELL THERAPY
Life Is A Laboratory
A Delhi doc's 'stem cell' therapy 'cures' patients. "Foul," cries the West. ...
Shruti Ravindran



Two years ago, 33-year-old Shannon Centman, an American Navy officer stationed in Port Huenme, California, fell asleep at the wheel. The next thing she knew, her car was wrapped around a pole, and she was being flung 50 feet back through the cold night air. Shannon resurfaced to find herself a paraplegic—"dead from the mid-back, all the way down". Her doctor told her she would never walk again. "I told him, 'I don't think so!'" Shannon recalls. "Oh, I can't wait to see him now! I'll walk in the door and say, 'How're you doing?' Now I can stand up with the help of callipers and I can use the rest-room like a normal human being!"

The turnaround took place, Shannon says, after just six weeks at Dr Geeta Shroff's Delhi clinic, Nutech Mediworld, where regular injections of human embryonic stem cells (hescs) were administered to her. She's not the only one to have been wheeled out of this clinic, dizzy with hope and exhilaration. A fortnight ago, Australian motivational speaker Perry Cross, a quadriplegic who'd been paralysed by a rugby accident at the age of 19, said he could breathe without his ventilator after two months of treatment from Dr Shroff. "I feel that by coming here, my lottery numbers have finally come up," he told the world media.


Dr Geeta Shroff

You'd think Dr Geeta Shroff, the architect of these miracles, and, according to her, 500 others as well, would be hailed as something of a genius, if not a Jesus. Instead, she's been labelled a "maverick" dabbling in "dangerous quackery" by the western media and medical establishment, ever since she declared three years ago that she'd used hescs to successfully treat 100 patients with a host of incurable and terminal illnesses—including Alzheimer's, multiple sclerosis, renal failure and cerebral palsy.

The medical establishment abroad agrees that certain stem cells contained in the "blastocyst" (a five-day-old human embryo) are capable of unlimited growth, and that their ability to differentiate into any tissue of the body may hold the key to a number of diseases we now consider irreversible and incurable, including degenerative conditions like Alzheimer's and Parkinson's.

Yet, despite the hype, the hope and the headlines this science generates, and the huge amounts of research money it attracts, it remains poorly charted territory due to the stringent laws restricting it in most countries, largely due to the ethical question of destroying a potential life to harvest embryonic stem cells. In India, hesc research and therapy isn't under legislation yet. There are only a set of non-enforceable guidelines, put into place in 2005 by the bioethics committee of the Indian Council of Medical Research (ICMR). The fact that India does not have legislation to regulate stem cell treatment is seen as a loophole or a "grey area of governance" abroad. But the occasional headlines that stem cell research generates abroad—about the uncontrollable neoplasias (cancers) it has unleashed in rats, for example—do seem to suggest that caution is far from unwarranted.

Dr Shroff, who had earlier specialised in IVF treatment for infertility, would beg to differ. She's certain that the criticism she's attracted is due to sour grapes from Western scientists consigned to labs, toiling over transgenic (not purely human) stem cell lines. Their refusal to acknowledge that the technology is ready for use on humans is financially motivated, she says, adding: "Anyone who's first is controversial, and I'm a woman, an Indian woman, and not a grey-haired woman."

"We're standing at the forefront of a new medicine that will change all medicine," she thrills.


Next
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(1 of 2)


Life Is A Laboratory


Previous
1
(2 of 2)
"Like when penicillin changed the world, and brought in the antibiotic era, and people no longer died of infections.... With hescs as the first line of treatment, the word incurable has to exit from the doctor's and patient's dictionary. My ready-to-use injections should be made available in pharmaceutical companies around the world, as easily as insulin or any antibiotic."

What irks the medical establishment, though, is that Dr Shroff hasn't disclosed what exactly these injections contain, in peer-review journals. Her defence: "What's peer, who's peer? Where do I have a colleague who understands what I do?" She's "totally above board", she insists, pointing out the reams of certifications her two clinics have been granted: ISO, GMP (Good Manufacturing Practices), GLP (Good Laboratory Practices) and GCP (Good Clinical Practices). She adds she's adhering to ICMR guidelines, and has formed an ethics committee to clear each and every patient's case.

All that's different about her case, Dr Shroff says, is that instead of publishing in journals and exposing her work to "rubbishing and theft", she's applied for a patent to protect her research. With a touch of asperity, she exclaims, "I don't know what upbringing (Western scientists) have to speak out of turn when they don't know me or my work. Remember," she adds, "I'm a doctor as well as a scientist. They may be capable scientists who understand what goes on in the lab, but they don't know how to get it into a clinic. They're doing research, but they're all doing research on rats, on mice! That's the difference between them and me."

And that, says Dr Vasantha Muthuswamy, ICMR senior deputy director-general and head of its bioethics committee, is unfortunately all too true. "Our contention is that this is experimental therapy, it's not accepted as standard therapy anywhere in the world, so it should proceed as clinical trials. But according to Dr Shroff, it's regular treatment." The pretext of protecting intellectual property is no excuse for secrecy, she adds: "We're not asking for the process, we would just like to know what she's injecting into her patients. If it's stem cell culture material, that can be easily shown under a microscope, and it can't be stolen." Sighing, she says, "I'd be the happiest if she really cured these patients.... But we don't know what's been injected, or of its scientific outcome. So the problem is that Dr Shroff is treating humans as rats and mice."

Shannon, however, couldn't be a happier mouse. "I think it's a miracle and other people need to know about it. When I go back, I'm heading straight to the Veteran's Hospital, going room-to-room and recommending this treatment to everybody, personally." That ought to stir things up even further in this bioethical Pandora's Box.
http://www.outlookindia.com/full.asp?fodname=20080623&fname=Doctor+%28F%29&sid=1

Multiple Sclerosis Society of Canada - Research


MS Research Teleconference

Dr. Paul O’Connor

On April 3, 2008, the MS Society of Canada hosted the annual MS Research Teleconf-erence. This year, Dr. Paul O’Connor discusses the latest in MS research and takes questions from callers. Listen to audio recording.
Stem Cells

Stem Cell Research
What is the promise of stem cell research in relation to multiple sclerosis? Find out more

http://www.mssociety.ca/en/research/default.htm


In T Cell Stimulation Cell Surface Receptors Are All 'Talk'
Understanding the mechanisms that drive healthy immune responses is important when it comes to combating autoimmune diseases, which occur when cells that should attack invading organisms turn on the body instead.

BioMS Medical Announces First Quarter 2008 Results
PharmaLive.com (press release) - Newtown,PA,USA
The trial will include trial and has recommended it continue. The trial is expected to for the treatment of relapsing-remitting MS (RRMS). ...
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Life Is A Laboratory
Outlook (subscription) - New Delhi,India
... multiple sclerosis, renal failure and cerebral palsy. The medical establishment abroad agrees that certain stem cells contained in the "blastocyst" (a ...
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McMaster Stem Cell and Cancer Research Institute

TheStar.com | Science | McMaster breakthrough boosts stem cell hopes
The researchers found that human embryonic stem cells – "the great grandmothers" of ... director of the McMaster Stem Cell and Cancer Research Institute. ...

Vitamin D-New way to treat heart failure
IndiaEduNews.net - New Delhi,India
Washington: The list of benefits conferred by Vitamin D has just got longer. It also keeps the heart fit as a fiddle, besides developing strong bones, ...
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Sunday, June 15, 2008

Cure for a host of autoimmune diseases

Hopkins Medicine Magazine - go home
Current Issue Past Issues Talk to Us About the Magazine Search
an online version of the magazine Winter 2007
Features
Michael Fletcher
PHOTOS BY Chris Hartlove



Convinced they hold the cure for a host of autoimmune diseases, Hopkins researchers have refused to give up in the battle for acceptance. Now success is in sight.

BY Elaine Freeman




Becky Lovelace was living on transfusions and losing blood almost as fast as she received it. It was 1977, and life expectancy for patients with severe aplastic anemia was a year, unless they had a matched bone marrow donor. Becky, 24, had no donor and had failed all standard treatments.

That was the grim picture when her desperate parents brought her to Lyle Sensenbrenner at Johns Hopkins Hospital. He had just one possibility to offer, and it was a long shot: high doses of cyclophosphamide (HiCy) could destroy Lovelace’s bone marrow, the factory for her blood cells, and whatever was causing her body to attack them. Then, if she were lucky, a healthy immune system might reboot.

The theory was untested, but it seemed to explain an unexpected observation in another patient with severe aplastic anemia (SAA)—a 19-year-old who had received HiCy to prepare him for a bone marrow transplant from his sister the year before. The transplant hadn’t taken. As his blood counts recovered post-transplant, they were not his sister’s cells, they were 100 percent male, his own cells—but they had recovered. Perhaps, Sensenbrenner mused, cyclophosphamide alone was responsible for the cure.

He had to be candid with Lovelace: “This treatment may kill you faster than your disease.” Despite the great risks involved—Lovelace would be gravely vulnerable to infections for weeks—she and her parents agreed to the experimental treatment. For four consecutive days she received HiCy infusions, suffering the acute toxicity familiar to patients on chemotherapy. Then for two weeks she had very few red blood cells, white cells, or platelets. “I was chewing my fingernails down to the cuticles,” Sensenbrenner admits. “Finally, after two weeks her blood counts began to go up, at first gradually and then faster. We breathed a tremendous sigh of relief.”

Over the next decade, Sensenbrenner used HiCy to treat 10 patients with this often fatal disease. But when he left Hopkins in 1987 to accept a job in his native Michigan,
the series stopped—and so did any follow-up to determine long-term outcome.

That’s how things stood in 1994 when Robert Brodsky
finished a fellowship in hematology at the National Institutes of Health and was hired by Johns Hopkins for an oncology
fellowship. Casting about for a clinical project for his newest protégé, who had a long-standing interest in aplastic anemia, Richard Jones, director of the Hopkins bone marrow transplant program, suggested that Brodsky track down the original 10 HiCy patients.

What Brodsky found, he recalls, was “shocking.” Not just that six were alive and well (a seventh had died not from SAA but from transfusion-transmitted AIDS). “But their blood counts were normal. We weren’t used to seeing such counts even with patients who responded to standard therapy.” And unlike patients on standard therapy (ATG or cyclosporine), the HiCy group hadn’t been on any immunosuppressive
medications for a decade. Seven of the 10 had been cured
of aplastic anemia by HiCy. With the evidence so clear, it was more than time, Brodsky and Jones realized, to start
investigating HiCy seriously as a cure for SAA—and potentially for the 80 other autoimmune diseases (from multiple sclerosis to myasthenia gravis) that plague more than 8 million Americans.

They immediately launched a new study, and five years
later, in 2001, published results showing they had cured 12 of 19 additional SAA patients treated with HiCy. After the article appeared in Annals of Internal Medicine, rejoicing seemed in order. Indeed, this magazine celebrated the accomplishment with a cover story.

Surprisingly, the article drew strong responses, both positive and negative, from distinguished School of Medicine alumni who received the magazine. One called Hopkins
to learn more about the treatment Brodsky and Jones were pursuing, then told anyone who would listen, “I can’t name another Hopkins contribution to clinical medicine that comes close to matching this technology,” said this successful entrepreneur. “If these guys don’t pick up a Nobel Prize someday, I will be shocked.”

But among some members of the medical community
outside Hopkins, there was strong opposition to using HiCy as a treatment for autoimmune diseases. Researchers at the NIH had conducted a randomized trial, reported in Lancet the prior year, which had been prematurely terminated. The
reason? The treatment had proved too toxic, they said, and entailed “much higher requirements for supportive care.”

Brodsky and Jones launched an effort to defend the
Hopkins protocol. In letters to the editor of Lancet and Annals of Internal Medicine, they pointed out that the NIH study differed from the Hopkins approach. NIH researchers started cyclophosphamide concomitantly with another drug [cyclosporine] that “may increase toxicity” and block “a potential mechanism of action for cyclophosphamide.” But the damage to more widespread acceptance of HiCy treatment was done.

Gloom. Brodsky and Jones knew their treatment would never emerge from under the radar screen without a convincing, multi-center, randomized trial. Such trials are so expensive, only two sources have the deep pockets to fund most of them: the government (usually the NIH) or a pharmaceutical company. With no apparent intellectual property to license—cyclophosphamide was a generic compound, off-patent for 30 or 40 years—cross out the pharma funding route. That left the NIH as a logical source for funding.

Neither Jones nor Brodsky was prepared for the response to their grant application from the NIH study section, though perhaps they should have been. Not only was the Hopkins proposal roundly rejected, one reviewer asserted that to conduct the study would be “unethical.”

*****

At other institutions, with both the NIH and pharma funding doors closed, that might be the end of the story. Fortunately for Jones and Brodsky, at Johns Hopkins they were surrounded by a community of clinician-scientists who shared their passionate belief that autoimmune diseases can be cured—not just treated but cured, or at least put into remission for extended periods—using the disputed HiCy protocol. (See “What Does ‘Cure’ Really Mean?” sidebar.) Neurologists, dermatologists, rheumatologists, each had published pilot studies with Brodsky documenting the protocol’s success with conditions ranging from lupus to multiple sclerosis, from scleroderma to myasthenia gravis.

There was general agreement among the Hopkins doctors about an important nuance (in addition to the altered drug protocol) separating their trials from the one at the NIH that had fared so badly: a system in place to provide the “much higher requirements for supportive care” during what could be a very rough and lengthy recovery period. HiCy treatment is not for the faint of heart. Because it wipes out the bone marrow and leaves patients with no functioning immune system, it leaves them vulnerable to any passing germ, virus, or fungus, until their stem cells can reconstitute bone marrow and blood products.

“The secret weapon here,” says Hopkins neurologist Daniel Drachman, “is IPOP,” the inpatient/outpatient care continuum program at Hopkins’ Sidney Kimmel Comprehensive Cancer Center. Whatever their autoimmune disease diagnosis, and whoever their admitting physician, patients
receiving HiCy treatment were overseen by the bone marrow transplantation (BMT) service and IPOP nurses accustomed to caring for people undergoing extreme courses of chemotherapy. During treatment, these patients live in nearby residences, returning daily to the same care team for testing, for prophylactic antibiotics, and for growth factors to stimulate bone marrow recovery.

“These patients must be under surveillance seven days a week until their blood counts come back up,” says Drachman, who has been working to eliminate myasthenia gravis (MG) for the last 25 years using HiCy. “If they crash on a weekend, there must be someone who knows what to do.” With the slightest fever, they’re readmitted to the hospital and aggressively treated. Risk management—informed by three decades of institutional experience administering the HiCy treatment—is a vital part of the Hopkins protocol.

Determined not to give up, Hopkins clinician-scientists decided to try a different strategy to gain funding for a
multi-center trial: Avoid severe aplastic anemia, the focus of the disputed studies, and focus instead on a different autoimmune disease. Multiple sclerosis (MS), striking approximately 400,000 people in the U.S. each year, offered the best chance for recruiting enough patients to complete a definitive study in a reasonable length of time. And Hopkins researcher Douglas Kerr had preliminary results showing HiCy could do better than just slow progression of the debilitating disease—it could potentially cure it. (See “Like Stomach Flu with a Goal,” below.)

Another good reason to shift to multiple sclerosis: the
duration of low blood counts following HiCy treatment for autoimmune conditions other than SAA is much shorter, leaving patients far less vulnerable. That’s because the immune system’s targets in SAA are the stem cells required to regenerate bone marrow.

Hopkins researchers and others had discovered in the 1980s that while HiCy destroys most of the body’s blood cells—and with them the out-of-whack immune system—stem cells are protected by an enzyme, aldehyde dehydrogenase, that inactivates cyclophosphamide.

“Patients with aplastic anemia come in with neutropenia [no red cells, no white cells, no platelets],” explains Brodsky. “Their bone marrow is practically wiped out of stem cells, while in other autoimmune diseases, patients have hundreds of times more stem cells to start with.” Consequently, says Brodsky, “the average time blood counts are down in patients with multiple sclerosis is only eight days, versus 50 with aplastic anemia.”

Together neurologists Kerr and Drachman wrote the clinical trial grant application, with Kerr to serve as principal investigator. He submitted the application to the NIH once, and was rejected. A second time: rejected. Application to the National Multiple Sclerosis Society: rejected. Each time the concern was about patient safety. “One reviewer said it was ‘too risky an approach for a disease such as MS,’” recalls Kerr, shaking his head. “But MS is a devastating disease. As one of my patients said, ‘Mortality is not defined by stopping of the heart, but by when you can’t do things that mean a lot to you in life.’”

Nevertheless, “after three rejections,” says Kerr, “we were pretty much done. We didn’t know how we’d do the multi-center trial on our own.” It was 2005, and his grant applications, as well as Brodsky and Jones’, had been turned down. Only a gift from a local philanthropist was allowing a small trial of HiCy against MS to proceed.

*****

At this point, an unexpected player re-entered the scene: Frank E. O’Donnell Jr., the entrepreneurial alum, who had pinned such high hopes on the protocol.

1 1 1

WHAT DOES CURE Really MEAN?

The word “cure” is a tricky thing. “HiCy is a cure, like bone marrow transplant is a cure,” says Hopkins hematologist Robert Brodsky. “There are aplastic anemia patients who are cured 10, 20, 30 years out after HiCy. If you’re not going to call that a cure, then none of us is cured of anything.” But he’d really prefer to call HiCy a “potential” cure, because, “If you use the word ‘cure,’ people think everyone is cured, though 40-50 percent may not be.”

Despite his caution in stating the case for HiCy as a total cure, evidence is clear that patients treated with HiCy must be reimmunized with all the childhood vaccines, starting a year after treatment. They react as if they have naïve immune systems.

“Rebooting the immune system” as an analogy for HiCy treatment was coined by Hopkins neurologist Daniel Drachman. He emphasizes that just as rebooting a computer doesn’t wipe out all of its memory, for most people HiCy doesn’t wipe out the entire mature immune system.

Judging from his work with myasthenia gravis, “What we’re doing is setting back the immune thermostat to a lower level, setting the clock back,” so patients previously refractory to standard treatment are treatable. “They’re not cured in the sense that they’re better forever,” Drachman explains. “Some myasthenics are in good shape off of medicine for 10 years, then bingo, it’s back.”

“Buying time” by rebooting rather than curing forever is an explanation that also makes sense to Noel Rose, director of the Johns Hopkins Autoimmune Disease Research Center, since the immune system that’s reconstituted starts with the same stem cell progenitors as the original. “MS doesn’t usually occur until age 25 or 40,” he points out. “Most patients are willing to buy 25 years.” — EF

“He’s the total package,” says Wilmer Institute Director Peter McDonnell. “He’s brilliant and has succeeded in multiple venues: ivory tower, business, practice. He had a stellar career here, and his professors hoped he’d continue in an academic career. But he’s also a tough, focused businessman, and a lot of academics have a problem with that.”

O’Donnell came to the Johns Hopkins accelerated program in 1971 after two years at St. Louis University, received his Hopkins B.A. in 1972 and M.D. in 1975, did his internship in Florida, then returned to Hopkins for training in
ophthalmology and plastic surgery. At 29, he completed the Wilmer chief residency and left to become chairman of ophthalmology at St. Louis University.

At some point, O’Donnell decided he wasn’t “bright enough to be a discoverer,” but recognized that he was good as an “enabler.” Starting off as a “passive” medical venture capitalist, he helped bring to market “lasik,” laser eye surgery to reduce dependency on glasses or contact lenses. Then 10 years ago, at age 48, O’Donnell started devoting all his efforts to technology transfer and formed his own company, Hopkins Capital Group (HCG), a privately held limited partnership that serves as an umbrella for niche pharmaceutical firms. “It’s not a career path I would have predicted,” he says, “but I love what I’m doing.”

The tag line of O’Donnell’s new company: “Key Funding for Disruptive Technologies.” Just as lasik “disrupted” the way vision problems are corrected, creating an opportunity for a specialized laser manufacturer, “if a little company can get FDA approval,” O’Donnell maintains, “it can drive the field, as there’s no competition.”

One of the companies in HCG’s portfolio, Accentia Biopharmaceuticals, acquires what it perceives as disruptive drug products in late-stage clinical development. Based on ingredients already approved by the FDA for other indications, these products usually are eligible for an accelerated regulatory approval pathway.

“From the time I first read about Rob and Rick’s work,” says O’Donnell, “I was convinced that this was a very, very important advance in clinical medicine.” For someone interested in profitable disruptive technologies, the lure of HiCy as a treatment for millions of people with autoimmune diseases was tantalizing: “Let’s not treat autoimmunity,” proclaims O’Donnell. “Let’s eliminate it and restore function!” Ever the entrepreneur, he likes to describe HiCy as “16 hours to a cure: four hours a day for four days in a row.”

To some, the business challenges of bringing this product to market might have seemed overwhelming: apparently no intellectual property to license and a technology requiring considerable clinical trial expenses for a generic drug.

“I was slow about solving the obstacles,” admits O’Donnell, “but I was also not going to give up. I kept in touch with Rob and Rick periodically as I noodled on trying to solve these barriers. It took me a few years, but I came up with a commercialization strategy based on the need to implement a system of care…to ensure patient safety.” The costs of the medicine and of a risk management program would be bundled together.

Thalidomide had served as a precedent. Abandoned for decades after research linked its use in pregnant women to birth defects, thalidomide had moved out of the shadows and gained approval as a treatment for leprosy and for multiple myeloma. Coupled with a risk management package, it was now being marketed as “Thalomid.”

As O’Donnell saw it, “The outstanding safety profile achieved at Hopkins was the result of a systematic approach” to minimize morbidity, i.e., the nuances. He believed he could make this “system of care” an integral part of a patent and of a new drug application to the FDA.
When he returned to Brodsky with this plan in 2005, he was met with skepticism. “It didn’t make a whole lot of sense to me,” says Brodsky. “I pulled Rick in, and it didn’t make sense to him, either, so we pulled the tech transfer people in, and they said O’Donnell was legit.” Furthermore, he was willing to “de-risk” the next steps for Hopkins by agreeing to pay up front for all patent drafting and prosecution.

O’Donnell’s company ultimately selected a “process patent” similar to the route used to patent new applications for thalidomide. They branded HiCy as Revimmune and determined to move forward using multiple sclerosis as the focus for a proposed large-scale clinical trial.

Throughout the past year, a string of press releases from Accentia traces Revimmune’s path to market, from acquisition of “exclusive worldwide rights for Revimmune ™,” to a pre-Investigational New Drug (pre-IND) meeting with the FDA. The results of that meeting, says Kerr, were encouraging: The FDA indicated its support for Accentia to submit an IND for a Phase 3 clinical trial of Revimmune among patients suffering from an aggressive form of multiple sclerosis known as refractory, relapsing-remitting MS (RRMS).

What makes this MS trial different from any other filed with the FDA, says O’Donnell, is that it will use “restoration of function” as its endpoint. That’s based on results of a pilot study by Kerr that used HiCy to treat nine patients with RRMS—patients for whom all other treatments had failed.

“I thought at best we’d see no increased disability,” says Kerr. “Instead, we demonstrated a 41 percent average reduction in disability”—a reduction that persisted. Pretty heady stuff considering that the most potent therapy for MS on the market “shows a 17 percent increase in disability over two years,” says Kerr.

Brodsky and Jones now have their names attached to what might become a blockbuster drug patent, but remain bemused skeptics about its commercial viability. “I still don’t know how they’ll make money from something that’s been off-patent for 30 or 40 years,” says Jones. “But if filing for a patent was the only way to get a drug company interested enough to fund a big trial that might get the treatment out there, I was willing to go along.”

Brodsky concurs: “If it leads to a trial in MS that truly tests the treatment in a multi-institutional, randomized way, it will be worth it and will teach us things like whether HiCy should be used earlier or later in MS.”

Under conflict of interest regulations, neither Brodsky nor Jones will be allowed to “consent” patients in the MS trial, but can treat them if supportive care is needed, and, of course, now must include a disclosure statement with their publications (see p. 27).

*****

Last year, Hopkins sponsored a reunion to thank patients who had the HiCy treatment over the past 30-plus years. Among those present was petite Becky Lovelace, today 54 years old and working in a car dealership after a career that’s run the gamut from pumping gas to teaching, from repairing computers to wearing a hardhat in a steel mill. Her presence was stark evidence that, for some, HiCy truly is a cure, not just a treatment.

“I didn’t know I was the first until the reunion,” Lovelace confided recently. “Dr. Sensenbrenner took me aside and said, ‘If you hadn’t lived, I wouldn’t have continued my research and none of these people would be here today.’ It gave me chills to think I was part of something so big, that my life was really worthwhile.”

1 1 1
The illegal border crossing where he entered the United States.
> Two years after HiCy, Richard Bauer (foreground) has no disease activity, reports Doug Kerr (I).

For HiCy champions, the prospect of achieving broader acceptance for a treatment that’s helped close to 100 Hopkins patients with auto-immune diseases since 1977 seems closer than ever. But everything is relative. Although the pre-IND meeting at the FDA went well, Accentia probably won’t submit the IND application until early in 2008. Then comes the 30-day wait for the FDA’s response. Even if the FDA were to approve a clinical trial tomorrow, says Kerr, it would still take about a year to launch.

“Both Accentia and we at Hopkins have a lot of work to do. For example, we have to establish what centers have the competence to participate. We have to get personnel on the ground familiar with the protocol at each center and work with them on IRB submissions.” To recruit approximately 270 patients with RRMS for the trial, Kerr estimates, “We need to get 12 to 15 groups throughout the country attached to a center such as the Hopkins BMT service that can provide intensive supportive care. Otherwise, a patient could die from a fulminating infection.” But he’s optimistic. At an October meeting of the American Neurological Association, where he shared his recent results, neurologists from 20 centers expressed interest in joining the trial. So perhaps the tide finally is turning.

While Kerr prepares for the big clinical trial, Brodsky, Jones, and their BMT colleagues Ephraim Fuchs and Leo Luznik continue to work on new uses for HiCy, particularly ways to enable transplants from partially matched (haploidentical) donors without triggering graft versus host
disease (GVHD). Two days of HiCy therapy three days after bone marrow transplant, for instance, cured sickle cell anemia in a young woman who had spent much of her life going in and out of hospitals. “Now any sickle cell patient who has a parent, child, or living sibling,” Brodsky beams, “is a transplant candidate! A half match is good enough.”

What’s sexy in science these days is treatment with stem cells. But Brodsky would tell you HiCy is treating patients with stem cells. They’re there; they’re the patients’ own stem cells. They just need to be protected from attack by an out of whack immune system and given the chance to regenerate. That is exactly what HiCy accomplishes.

Ironically, the struggle to gain acceptance for HiCy as a cure for autoimmune diseases parallels a much earlier struggle to convince the scientific community such conditions even existed. The “bible” of the field, The Autoimmune Diseases (now in its fourth edition and co-edited by Hopkins’ Noel Rose), opens with a chapter by immunologist/medical historian Arthur Silverstein titled “Autoimmunity: A History of the Early Struggle for Recognition.”

“It is one of the curious situations in science,” begins the chapter, “that certain well-demonstrated facts are refused entry into the body of accepted knowledge, and may become so effaced from the collective memory that they must be

rediscovered many years later in order to gain acceptance. Such was the case in immunology ... . In the end, it may be that ... . acceptance of a fact in science depends less upon its truth than upon its acknowledgment by the leaders in the discipline… However, the truth in science ultimately emerges, although sometimes it takes a very long time.”*




Under a licensing agreement between Accentia Pharmaceuticals and the Johns Hopkins University, Drs. Brodsky and Jones are entitled to a share of royalty received by the university on sales of intellectual property (Revimmune). The study described in this article could impact the value of Revimmune. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict-of-interest policies.





HiCy at Hopkins: A Timeline

“It takes 50 years to get a bad idea out of medicine and 100 to get a good idea in.”
—Hughlings Jackson


“We’re almost half way there.”
—Richard Jones

1969: George Santos proves high-dose cyclophosphamide (HiCy) is toxic to diseased marrow and suppresses the immune system prior to bone marrow transplant (BMT).


1976: Severe aplastic anemia (SAA) patient treated with HiCy prior to bone marrow transplant from sister recovers, but, unexpectedly, with his own cells.

1977: First SAA patient purposely treated with HiCy without bone marrow transplant.

1977–87: Ten patients treated with HiCy for SAA.

1980's: Scientists show mechanism by which stem cells—but not lymphocytes—survive HiCy, allowing “rebooting” of naïve immune system.

1982: Studies of HiCy for myasthenia gravis (MG) start in animals.

1987: Lyle Sensenbrenner leaves Hopkins; SAA series stops.

1994: Robert Brodsky and colleagues start follow-up of 10 SAA patients.

1996: Pilot study results published, showing 7of 10 patients “cured.”

1998: HiCy success against lupus pilot study published.

1999: HiCy success against pemphigus published.

2001: Results from 19 SAA patients published, showing durable, treatment-free remission in 65 percent.

2001–07: Publications document HiCy success against post-transplant graft versus host disease, autoimmune hemolytic anemia, refractory myasthenia gravis (MG), multiple sclerosis (MS), lupus, scleroderma, other autoimmune diseases.

2002–05: NIH rejects clinical trial grant applications for HiCy vs. SAA and MS.

2006: HiCy patent application filed.

2007: Accentia licenses HiCy, names it Revimmune, and plans to file pre-investigational new drug application with FDA for Phase 3 clinical trial for MS.






LIKE STOMACH FLU WITH A GOAL

Richard Bauer was on his feet all day as a machine operator, and working nights at a local steakhouse, when the symptoms first started. “I felt like my feet were wrapped tightly, like I had on 10 or 12 pairs of socks,” he recalls. “Within months, numbness and tingling traveled up my trunk, then down my left arm. My feet got really heavy, as if I had lead weights in my shoes, and my coordination began to go.”

Bauer’s life descended into a nightmare round of appointments with different doctors at different hospitals before he was diagnosed with multiple sclerosis (MS). His own immune system was attacking his body, stripping the myelin coating from his central nervous system.

Soon he was in a wheelchair, had lost hearing on the left side, and was forced to move back in with his family. Six months out of work, his insurance ran out, “But my parents insisted I keep an appointment with Dr. [Doug] Kerr in June 2005,” he recalls.

Kerr told Bauer and his parents about a “very intense” treatment with high doses of cyclophosphamide (HiCy), which kills off disordered cells so a patient’s own stem cells can regenerate and reboot a properly-functioning immune system. He was conducting a study of HiCy’s effectiveness against MS.

“MS was taking my life. I had to attack it as aggressively as it attacked me,” says Bauer. “‘If there’s a chance to fix me,’ I told Dr. Kerr, ‘then fix me.’”

Before he could be accepted for the protocol, Bauer went through two months of testing to make sure his heart and lungs could survive it. To be sure he understood the treatment’s risks—even a risk of death—and was capable of making an informed decision; he also agreed to a psychiatric evaluation.

Bauer was admitted to Hopkins Hospital on September 27, 2005, for four consecutive days of HiCy infusion. He’s candid about what happened next: “I didn’t feel bad until the second or third day. That’s when I got really sick, like a stomach virus… Every time I went to the bathroom, I felt like I was on fire.”

He went home after the fourth day, but came back daily to have his blood counts checked and for vancomycin [antibiotic] infusions. “That was the worst! I was allergic to it. I had hives from the top of my head to the bottom of my toes. I felt like I was burning up, but I had to take it for seven days.”

Blood counts dropping to 0 were a good sign and a warning. That meant his old immune system had been destroyed, but that he was vulnerable to every passing germ. A week of a special growth hormone stimulated his stem cells to do their rebuilding, and after four weeks, things started to reverse.

“I started walking to the bottom of the street and back, at first with a cane, and it took a long time,” he says. Gradually the distance increased and the time decreased. “I went from one block to a half-mile to two miles.” Today, Bauer runs 2 1/2 miles a day.

Back for his 24-month follow-up in October, the 30-year-old was the picture of health. With a diamond stud in his left ear, he’s six feet tall, sports a shaved head, and wears fashionable rimless glasses.

The good news for Bauer is that his “attack” against MS appears to have worked. Kerr found no disease activity by any measure. “In terms of a cure,” he admits, “it’s probably too soon to know for sure. It’s possible that he will reactivate over time. But for now, we couldn’t have hoped for any more with him. ”

Bauer was one of nine patients accepted into Kerr’s study (funded through a private donation). Seven in the group had a statistically significant reduction in disability and restoration of function. Bauer’s newfound good health inspired him to return to college for a second degree, and he exudes optimism and good humor. “The treatment certainly wasn’t pleasant,” he says, “but it was no worse than stomach flu, and at least it had a goal. Conventional drugs wouldn’t have done much for me other than prolonging the inevitable. If [HiCy] were 10 times worse, it would have been worth it. ”

EF




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