Hoping Two Drugs Carry a Side Effect - Longer Life - NYTimes.com
Teva Enrolls Patients for Second Phase III Trial of Laquinimod
FDA news (subscription) - Falls Church,VA,USA
BRAVO, a randomized, double-blind, parallel-group, placebo-controlled study, will compare the safety and efficacy of laquinimod with placebo, as well as the ...
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Tysabri
Biogen Idec reports strongsecond quarter results
Bizjournals.com - Charlotte,NC,USA
Newer MS drug Tysabri, nearly derailed by safety issues a few years back, generated $147 million in sales during the quarter, up 210 percent over the same ...
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UPDATE 2-Biogen profit up 11 pct, Tysabri shines
Reuters - USA
O: Quote, Profile, Research) on Tuesday reported a better-than-expected second-quarter profit as sales of closely watched multiple sclerosis drug Tysabri ...
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Biogen Idec raises 2008 outlook on drug sales
Forbes - NY,USA
... its full-year profit and revenue outlook Tuesday, citing continued expectations for higher sales of the multiple sclerosis drugs Avonex and Tysabri. ...
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Biogen Idec and Elan Celebrate Second Anniversary of TYSABRI(R ...
PR-Inside.com (Pressemitteilung) - Wien,Austria
announced the two-year anniversary of TYSABRI(R) (natalizumab) as a treatment for relapsing forms of multiple sclerosis (MS), marking the reintroduction of ...
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Elan, Biogen say over 31000 patients using Tysabri
MarketWatch - USA
By Elena Berton , , ) Tuesday said that, at end-June, their multiple sclerosis treatment Tysabri was being used on more than 31800 patients, two years since ...
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Biogen Idec marks anniversary for Tysabri
Boston Globe - United States
As of the end of June, more than 31800 patients worldwide were estimated to be receiving Tysabri, a treatment for relapsing forms of multiple sclerosis, ...
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Biogen Idec's 2Q profit rises 11 percent
CNBC - Englewood Cliffs,NJ,USA
NEW YORK - Biotechnology company Biogen Idec says profit rose 11 percent on increasing sales of its multiple sclerosis treatments Avonex and Tysabri. ...
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Elan's Tysabri patient number impresses analysts
Reuters - USA
I: Quote, Profile, Research) said on Tuesday that more than 31800 patients worldwide were receiving its multiple sclerosis (MS) drug Tysabri at the end of ...
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Elan's Tysabri patient number impresses analysts
Reuters - USA
I: Quote, Profile, Research, Stock Buzz) said on Tuesday that more than 31800 patients worldwide were receiving its multiple sclerosis (MS) drug Tysabri at ...
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Biogen Idec and Elan Celebrate Second Anniversary of TYSABRI(R ...
MarketWatch - USA
today announced the two-year anniversary of TYSABRI(R) (natalizumab) as a treatment for relapsing forms of multiple sclerosis (MS), ...
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Biogen Idec Isn’t Sweating Possible Sale of Genentech to Roche
Xconomy - Cambridge,MA,USA
Irish drugmaker Elan, Biogen’s partner on marketing the multiple sclerosis drug Tysabri, has a similar buyout right if Biogen gets bought, ...
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Opexa Conducts Additional Analysis on Phase I/II Extension Study ...
MarketWatch - USA
a company leading in the development of cell therapies for multiple sclerosis (MS) and diabetes, has completed an internal assessment of data from its Phase ...
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Market Report -- Short Stories (ACOR)
MSN Money - USA
Firm believes the large market opportunity exists for Fampridine-SR, both upon market introduction as well as in long-term use. ...
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Milestone for cannabinoid MS study
EurekAlert! Mon, 21 Jul 2008 8:51 AM PDT
The CUPID (Cannabinoid Use in Progressive Inflammatory brain Disease) study at the Peninsula Medical School in Plymouth has reached an important milestone with the news that the full cohort of 493 people with multiple sclerosis (MS) has been recruited to the study.
Important vitamin D does the body good
Daily Herald Sun, 20 Jul 2008 10:08 PM PDT
It's being hailed as a protection against a plethora of cancers, cardiovascular and autoimmune diseases, multiple sclerosis, rheumatoid arthritis, type 1 diabetes and even chronic back pain.
Study To Investigate Link Between Cannabis Compound And Slowing Of Multiple Sclerosis
Medical News Today Tue, 22 Jul 2008 5:10 AM PDT
The CUPID (Cannabinoid Use in Progressive Inflammatory brain Disease) study at the Peninsula Medical School in Plymouth has reached an important milestone with the news that the full cohort of 493 people with multiple sclerosis (MS) has been recruited to the study.
Important vitamin D does the body good
Daily Herald Tue, 22 Jul 2008 9:53 AM PDT
It's being hailed as a protection against a plethora of cancers, cardiovascular and autoimmune diseases, multiple sclerosis, rheumatoid arthritis, type 1 diabetes and even chronic back pain.
New island invasion as researchers seek Viking link with MS
The Scotsman Mon, 21 Jul 2008 4:37 PM PDT
Orkney and Shetland are the focus of a new study investigating a possible genetic cause for multiple sclerosis, which is more prevalent in the far north than anywhere else in
Research News
Summaries of all the latest research findings on MS selected by a team based at the Institute of Neurology, London.
Atlas of MS publication promotion work begins at MSIF
MSIF is working with the World Health Organization to produce the Atlas of MS. This major collaboration used a survey to determine the global epidemiology of MS and the resources to diagnose, inform, treat, rehabilitate, manage, support and provide services to people with MS in different countries.
HLA-DRB1(*)15 allele influences the later course of relapsing remitting multiple sclerosis
The role of genes in the pathogenesis of MS is complex. The authors found an association between this gene and the development of secondary progressive MS, suggesting that it may be somehow involved.
authors: Cournu-Rebeix I, Génin E, Leray E, Babron MC, Cohen J, Gout C, Alizadeh M, Perdry H, Semana G, Brassat D, Clerget-Darpoux F, Yaouanq J, Edan G, Rosenheim M, Fontaine B.
source: Genes Immun. 2008 Jul 10. [Epub ahead of print]
Brain responses to verbal stimuli among multiple sclerosis patients with pseudobulbar affect
The authors used a neurophysiological technique to study people with MS who had problems with emotional control. They found that people with problems with emotional control were more impulsive and that structures involved in sensory-motor and emotional processing seemed to be involved in this.
authors: Haiman G, Pratt H, Miller A.
source: J Neurol Sci. 2008 Aug 15;271(1-2):137-147. Epub 2008 May 27.
Peripheral nerve demyelination in multiple sclerosis
MS characteristically affects the central nervous system. The authors looked for demyelination in the nerves outside the brain and spinal cord in people with MS and found it in 5 percent of them.
authors: Misawa S, Kuwabara S, Mori M, Hayakawa S, Sawai S, Hattori T.
source: Clin Neurophysiol. 2008 Aug;119(8):1829-33. Epub 2008 May 20.
Mechanisms of action of disease-modifying agents and brain volume changes in multiple sclerosis
This article reviews the effects that different treatments for MS have on brain volume and the mechanisms of these changes.
authors: Zivadinov R, Reder AT, Filippi M, Minagar A, Stüve O, Lassmann H, Racke MK, Dwyer MG, Frohman EM, Khan O.
source: Neurology. 2008 Jul 8;71(2):136-44.
This study showed that this molecule was effective in reducing symptoms and central nervous system inflammation in the animal model of MS.
authors: Makar TK, Trisler D, Sura KT, Sultana S, Patel N, Bever CT.
source: J Neurol Sci. 2008 Jul 15;270(1-2):70-6. Epub 2008 Apr 18.
MS News
Summaries of MS news from websites around the world.
New Venezuelan MS Association
source: Asociación Venezolana de Esclerosis Múltiple
The Asociación Venezolana de Esclerosis Múltiple (AVEDEM) was established on 8 July 2008 in Valencia, Venezuela.
US: Researchers reprogramme adult stem cells in mouse brain to become myelin-making cells
source: US National MS Society
Researchers report that adult stem cells in mice that are on their way to becoming nerve cells can be redirected by changing a single gene to turn into cells that make nerve fiber-insulating myelin – the substance that is a key target of the immune attack in MS.
UK: New publication about MS and the law
source: UK MS Society
The UK MS Society have produced a new publication about MS and the law.
Spain: swimming fundraiser success
source: Federación Española Esclerosis Múltiple
The Federación Española Esclerosis Múltiple (FELEM) held Mójate 08 on 13 July 2008, with more than 92,000 people taking part.
Multiple Sclerosis International Federation
3rd Floor Skyline House, 200 Union Street, SE1 0LX
Tel: +44 (0) 20 7620 1911
Fax: +44 (0) 20 7620 1922
Registered Charity: 1105321
Email: info@msif.org
Women More Likely to Have Second Thoughts on Tattoos
http://www.nlm.nih.gov/medlineplus/news/fullstory_67187.html
Hoping Two Drugs Carry a Side Effect: Longer Life
Southern Illinois University School of Medicine
COUNTING CALORIES For a longevity study, this mouse is on a restricted diet.
Published: July 22, 2008
BOSTON, Mass. — One day last month, clad in white plastic garments from head to toe, Dr. David Sinclair showed a visitor around his germ-free mouse room here at Harvard Medical School.
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Graphic Caloric Restriction
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CJ Gunther for The New York Times
IN THE LAB Dr. David Sinclair is trying to develop drugs to extend health, and life.
The mice, subjects in studies of health and longevity, are kept in wire baskets under intensive nursing care. A mouse gym holds a miniature exercise machine that tests the rodents’ ability to balance on a rotating bar. In a nearby water maze, mice must recall visual cues to swim to safety on a hidden platform, a test of their powers of memory. Those that forget their lessons are rescued as they start to submerge and humanely dried out under a heat lamp, Dr. Sinclair assured his visitor.
Dr. Sinclair is a co-founder of Sirtris, a company that itself has been swimming in uncharted waters as it works to develop drugs that may extend the human life span. But it seemed to have found a safe platform last month when it was bought last month by the pharmaceutical giant GlaxoSmithKline for $720 million.
Sirtris has two drugs in clinical trials. One is being tested against Type 2 diabetes, one of the many diseases of aging that the company’s scientists hope the drugs will avert. With success against just one such disease, the impact on health “could be possibly transformational,” said Dr. Patrick Vallance, head of drug discovery at GlaxoSmithKline.
The new drugs are called sirtuin activators, meaning that they activate an enzyme called sirtuin. The basic theory is that all or most species have an ancient strategy for riding out famines: switch resources from reproduction to tissue maintenance. A healthy diet but with 30 percent fewer calories than usual triggers this reaction in mice and is the one intervention that reliably increases their life span. The mice seem to live longer because they are somehow protected from the usual diseases that kill them.
But most people cannot keep to a diet with a 30 percent cut in calories, so a drug that could activate the famine reflex might be highly desirable. Dr. Leonard Guarente, an M.I.T. biologist who founded the field of sirtuin biology, thinks the famine reflex is mediated through the sirtuin enzymes. Dr. Sinclair, his former student, discovered that sirtuins could be activated by drugs. The most potent activator that emerged from his screens was resveratrol, a natural substance found in red wine, though in amounts probably too low to be significant for health.
The Sirtris drug being tested in diabetic patients is a special formulation of resveratrol that delivers a bloodstream dose five times as high as the chemical alone. This drug, called SRT501, has passed safety tests and, at least in small-scale trials, has reduced the patients’ glucose levels.
The other drug is a small synthetic chemical that is a thousand times as potent as resveratrol in activating sirtuin and can be given at a much smaller dose. Safety tests in people have just started, with no adverse effects so far.
The hope is that activating sirtuins in people would, like a calorically restricted diet in mice, avert degenerative diseases of aging like diabetes, heart disease, cancer and Alzheimer’s. There is no Food and Drug Administration category for longevity drugs, so if the company is to submit a drug for approval, it needs to be for a specific disease.
Nonetheless, longevity is what has motivated the researchers and what makes the drugs potentially so appealing.
Dr. Christoph Westphal, the chief executive of Sirtris, said of the potential of the drugs, “I think that if we are right, this could extend life span by 5 or 10 percent.” He added that his goal was to develop drugs against specific diseases, with the extension of life being “almost a side effect of our medicine.”
Sirtris was founded in 2004 after Dr. Westphal, then working at a Boston venture capital firm, approached Dr. Sinclair. Because of widespread interest in the sirtuin activation idea, Dr. Westphal had little difficulty raising money and recruiting distinguished scientists to Sirtris’s advisory board.
He later decided to sell the company to GlaxoSmithKline, he said, because it was getting harder to raise money and clinical trials could proceed faster with the larger company’s resources. Sirtris was acquired at an 84 percent premium, better than the 50 percent at which most companies are bought, Dr. Westphal said.
The impact of Sirtris’s drugs, if successful, could extend beyond the drug industry. Dr. Guarente believes that many people might start taking them in middle age, though after having started a family because they may suppress fertility.
Mice on the drugs generally remain healthy right until the end of their lives and then just drop dead.“If they work in people that way, one would look to an extension of health span, with an extension of life as a possible side effect,” Dr. Guarente said. “It would necessitate changing ideas about when people retire and when they stop paying into the system.”
GlaxoSmithKline could put SRT501, its resveratrol formulation, on the market right away, selling it as a natural compound and nutritional pharmaceutical that does not require approval by the F.D.A. “We haven’t made any decisions, but that clearly is an option,” Dr. Vallance said.
If GlaxoSmithKline decides instead to seek F.D.A. approval, it will need to prove that resveratrol is safe in the large doses required for efficacy. Resveratrol seems to exert many influences on the body, some of which are not exerted through sirtuin. “None of us should be naïve enough to think resveratrol won’t have multiple effects, including some you don’t want,” Dr. Vallance said.
GlaxoSmithKline’s purchase of Sirtris has pushed the optimism of sirtuin researchers and others to new heights. “We are all holding our breath,” said Dr. Huber Warner, editor of the Journals of Gerontology. But the success of the drugs is far from assured.
Most potential drugs fail to make it past clinical trials, and the same may prove true for Sirtris’s candidates. The sirtuin-activating chemicals the company has designed could turn out to be toxic. Another uncertainty is that the underlying science is still in flux and debate rages among academic researchers over many details of how caloric restriction works.
Some biologists think that sirtuin is not the only mediator of the famine reflex, and that resveratrol may not work through sirtuin at all in exerting its beneficial effects on mice. “There are data both for and against that hypothesis, though that doesn’t dissuade one from pursuing it as a potential benefit,” said Dr. Thomas Rando, who studies aging in stem cells at Stanford University.
In initial tests in mice, resveratrol has doubled muscular endurance, lowered the bad form of cholesterol, protected against various bad effects of a high-fat diet and suppressed colon cancer. New reports are confirming some of these benefits, but others are ambiguous or puzzling.
According to a study published on July 3 in the journal Cell Metabolism by Dr. Sinclair and Dr. Rafael de Cabo of the National Institute on Aging, resveratrol given to aging mice reduced their cataracts, strengthened their bones, improved coordination and enhanced their health in several other ways. Yet despite their better health, the mice lived no longer than usual.
“Minimally this calls into question one pillar of the GSK investment,” said Dr. Ronald Evans, a leading expert on hormonal responses at the Salk Institute. Dr. Evans said that sirtuin research was promising but unproved, and that he did not agree that sirtuin was the probable mediator of the famine reflex, a concern that “calls into question the second pillar of the GSK investment.”
The frontiers of science are often turbulent, and it can take years for clarity to emerge from confusion. Dr. Westphal said the decision to ignore the academic debate about exactly how resveratrol may work was one of two principal reasons for Sirtris’s quick success. The other was to focus the company’s limited resources on developing just two drugs.
The researchers at Sirtris are no strangers to skepticism. Dr. Guarente and Dr. Sinclair were ridiculed when they first started looking for longevity genes more than 15 years ago, because aging was then considered to be an intractable problem. His colleagues, Dr. Guarente said, “thought I was nuts.”
Dr. Sinclair, when he first arrived as a young postdoctoral student in Dr. Guarente’s lab to work on longevity, was downcast to learn of the other students’ severe doubts. “The view even in Lenny’s lab was that this problem was going nowhere, it was a house of cards that would fall down any month now.” He called his parents in Australia to tell them he may have made a big mistake. But the research led eventually to the discovery of the sirtuinlike proteins and their role in extending the life span of yeast, worms and flies.
He and Dr. Guarente developed the sirtuin field with the hope of increasing longevity. But because of Sirtris’s focus on developing drugs that have the F.D.A.’s approval for specific diseases, both are being less explicit about their hopes of reversing aging. “There’s a much greater chance of a drug that can treat disease than of extending life span,” Dr. Sinclair said.
“I’m becoming more boring in my old age,” he added apologetically.
GlaxoSmithKline’s press releases refer to the sirtuins as “enzymes that the company believes control the aging process.” But Dr. Vallance is more guarded, saying aging is too hard to measure. The goal is not the extension of human life span; rather, “The prolongation of health is the aim,” Dr. Vallance said.
posted by Bill at 11:51 PM
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