Hopkins reports success with MS treatment -- baltimoresun.com
From Tuesday's Sun
Hopkins reports success with MS treatment
By Euna Lhee
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."
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