MEDICINE / MULTIPLE SCLEROSIS : Drug Seems to Halt Chronic MS in Test : Among 24 patients in the trial, only one got worse. But some experts caution that the study was for a short period and that cladribine is highly toxic.
An anti-leukemia drug developed at the Scripps Research Institute appears to halt the advancement of the chronic, progressive form of multiple sclerosis, a form for which there is currently no treatment, San Diego researchers reported Saturday.
Among 24 patients in a test group who received the drug cladribine, only one got worse after a year, while the condition of four others improved significantly. In contrast, seven of 28 test participants who received a placebo got significantly worse and only one improved, Dr. Ernest Beutler and his colleagues at Scripps reported Saturday in the international medical journal The Lancet.
MS affects an estimated 300,000 Americans, half of whom have the chronic, progressive form.
“There is no question in my mind that this is the first really effective treatment for this type of this disorder,” Beutler said in an interview.
But officials of the National Multiple Sclerosis Society cautioned patients against getting their hopes up because cladribine has been tested for only a short period and is highly toxic.
“If future clinical trials show it (cladribine) to be useful and safe, it will be an important finding,” said Dr. Stephen C. Reingold, vice president of the society. “But the results are not important if the drug cannot be used safely.”
Beutler said the toxic side effects can be significantly reduced by using lower doses of cladribine, which preliminary testing has also suggested will be effective in treating the disease. Such reduced doses will be used in a new multicenter clinical trial of the drug that will enroll 400 patients.
Multiple sclerosis is a progressive, often disabling disease of the central nervous system. It occurs when, for reasons that are unknown, the body’s immune system attacks the protective myelin sheaths surrounding nerve fibers. The process is much like scraping the insulation off an electrical wire, short-circuiting the transmission of nerve impulses that control muscle activity.
Patients can suffer loss of balance and muscle coordination, blurred vision, slurred speech, difficulties in walking and--in severe cases--paralysis. MS affects twice as many women as men, and two-thirds of all cases develop when the victim is between ages 20 and 40.
The only treatment for MS is a drug called beta-interferon, and it has proved useful only for treating patients with the so-called exacerbating-remitting form of the disease, which affects about 30% of victims. In this form, MS symptoms subside partially or totally after a flare-up, often re-erupting later.
There is no approved treatment for the chronic, progressive form of the disease, in which neural deterioration proceeds at a relatively steady rate.
Because MS results from an inappropriate attack on the body by the immune system, researchers have long speculated that drugs that suppress immune function could impede its progress. A large clinical trial in the 1980s showed that the drug cyclosporine, widely used to prevent rejection of transplants, could slow the course of MS. But kidney damage and increases in blood pressure caused by the drug outweighed its beneficial effects, and its use was abandoned.
Similar results have been reported with other drugs that impair immune function, but all have had disabling side effects, Reingold said. Promising reports appeared this year saying that the anti-cancer drug methotrexate--which is inexpensive and has few side effects--can also slow the disease. But the reported effects of this and other drugs were significantly less dramatic than those reported by Beutler’s team, Reingold said.
Beutler infused cladribine directly into patients’ veins twice a month for four months, then observed them for another eight months. The drug treatment apparently halted the progression of the disease in most patients, as measured by clinical symptoms, magnetic resonance imaging of damage to the brain and the presence of characteristic proteins in spinal fluid.
The results were so dramatic, Beutler said, that the trial was halted prematurely and the patients who had been receiving a placebo were treated with the drug.
One of the treated patients died from a previously contracted hepatitis infection. That death was not directly linked to the drug, Reingold said, but a hepatitis victim whose immune system was not suppressed might have been better able to fight it off. There were also several cases of herpes zoster (shingles), which is unusual in such a young population unless their immune systems are strongly compromised, he noted. That suggests the patients would be vulnerable to a variety of infectious diseases, he said.
Reingold and Beutler cautioned physicians against prescribing cladribine for MS patients until more trials have been conducted. “We are dealing with a drug that is potentially very dangerous and that could cause lots of complications,” Reingold said.
Beutler added that the long-term effects of cladribine have not been studied, and “it could cause cancer or leukemia five or 10 years down the road like many other anti-cancer drugs.”
MS patients who would like to enroll in the trials should call 1-800-SCRIPPS for information.
