[tt] 'HiCy' drug regimen reverses MS symptoms in selected patients | Science Blog

[Brian Atkins]

http://www.scienceblog.com/cms/hicy-drug-regimen-reverses-ms-symptoms-selected-patients-16650.html



A short-term, very-high dose regimen of the immune-suppressing drug 
cyclophosphamide seems to slow progression of multiple sclerosis (MS) in most of 
a small group of patients studied and may even restore neurological function 
lost to the disease, Johns Hopkins researchers report. The findings in nine 
people, most of whom had failed all other treatments, suggest new ways to treat 
a disease that tends to progress relentlessly.

"We didn't expect such a dramatic return of function," says Douglas Kerr, M.D., 
Ph.D, associate professor of neurology at the Johns Hopkins University School of 
Medicine. "Although we're very early in the game, we think this approach could 
be the linchpin of a significant advance for MS treatment."

Researchers have used the so called HiCy treatments with some success at Johns 
Hopkins for a variety of other immune system disorders, including aplastic 
anemia, lupus and myasthenia gravis.

Cyclophosphamide kills immune-system cells but spares the bone marrow stem cells 
that make them. The usual method of delivering it in pulsed, small doses, 
however, can cause the drug to build up to toxic concentrations in patients' 
bodies, causing a variety of side effects, including a greatly increased risk of 
infection.

Seeking an alternative way to use the drug, Kerr and his colleagues reasoned 
that HiCy might clear out the majority of a patient's immune system in one fell 
swoop, then allow it to "reboot," giving nerve cells a fresh start and an 
opportunity to repair themselves. In the current study, nine MS patients got a 
total single infusion of 200 milligrams per kilogram of cyclophosphamide 
intravenously over four days, a dose several times higher than that given in 
pulsed regimens but significantly lower than the total amount usually given 
patients over time.

Before treatment, Kerr says, the study participants were "the worst of the 
worst" among MS patients. Eight of the nine patients had failed conventional MS 
treatments, and several of them were wheelchair-bound.

Reporting in the June 9 Archives of Neurology, the Johns Hopkins team said the 
disease appeared to reverse course for seven of the nine patients over two years 
following treatments. Overall, the patients, men and women ranging in age from 
20 to 47 at the beginning of the study, experienced a 40 percent reduction in 
scores of a standard test that measures disability. They also had an overall 87 
percent improvement in scores on a composite test that measures physical and 
mental function.

MS, which affects approximately 400,000 people - predominantly women - in the 
United States, is believed to occur when the body's immune system attacks the 
insulating sheath that coats nerve cells, causing it to degenerate. 
Consequently, electrical signals that the cells use to communicate with the rest 
of the body become progressively weaker, leading to symptoms that include 
numbness, tingling, cognitive problems and sometimes paralysis.

Researchers have identified four different subtypes of MS, and each is thought 
to be caused by a different autoimmune process. As a result, developing a 
treatment that effectively targets all types of MS has been challenging, says Kerr.

Kerr cautions that the "reboot" phenomenon didn't work in all the patients. Two 
years after treatment, MRI images showed that the disease had reactivated in 
about half the study participants, suggesting that their renewed ability may not 
be permanent.

Kerr's colleague Adam Kaplin, M.D., Ph.D., assistant professor of psychiatry and 
neurology at the Johns Hopkins School of Medicine, is leading efforts to improve 
HiCy therapy with a blood test in development that could predict which patients 
would benefit the most from HiCy treatment. Also, since immune cells that regrow 
after HiCy treatment may contain the same defect that leads to MS, Kaplin and 
his colleagues are working on a way to regrow only healthy immune cells.

-- 
Brian Atkins
Singularity Institute for Artificial Intelligence
http://www.singinst.org/