Multiple sclerosis drug has clinical benefits

Apr 05, 2010

A drug whose clinical benefit in treating multiple sclerosis was discovered at Rush University Medical Center was approved by the Food and Drug Administration on January 22 and is now available in the U.S.

The drug, called dalfampridine, is the first therapy for multiple sclerosis that can be taken orally. It is also the first FDA-approved therapy to treat impaired walking, a debilitating symptom of the disease limiting patients' independence and ability to accomplish the most basic tasks of daily living. While other multiple sclerosis drugs work by decreasing the inflammation that causes damage to the , dalfampridine is designed to allow conduction of despite the damage.

Research that led to the discovery of dalfampridine's therapeutic value dates back to the 1960s, when Dr. Floyd Davis, then a neurologist in training and later a physician at Rush, became intrigued by an unusual clinical observation: many multiple sclerosis patients fare better when their body temperature is slightly lowered, even by just two- or three-tenths of a degree.

"In multiple sclerosis, the protective that wraps around nerve fibers in the brain and spinal cord is damaged, essentially causing a short circuit," said Davis, who is now retired. "Somehow, lower body temperature enabled the electrical pulse to continue its travel along the nerve fibers. I was completely transfixed by the significance of that fact."

It was important because it showed "that the damaged nerve fibers were not doomed, as previously believed," said Dr. Dusan Stefoski, director of the Rush Multiple Sclerosis Center, who teamed up with Davis in 1978, shortly after completing neurology training at Rush.

Davis launched a series of laboratory studies to understand the mechanism that explained the noticeable improvement in symptoms.

He then looked for a compound that could mimic some of the effects of lower body temperature and learned of 4-aminopyridine, or dalfampridine, which blocks the potassium ion channels in nerve fibers.

"The chemical was commonly used in physiology laboratories where scientists were studying normal nerve conduction, but at the time it was used clinically only by physicians in Bulgaria, then a Communist-block country," Davis said. "They didn't know how it worked, but they used it to help patients recover from anesthesia-induced paralysis more quickly."

In 1983, in a small proof-of-concept study, Davis and Stefoski injected the drug in 11 patients whose motor function and eyesight were impaired because of multiple sclerosis.

"It was stunning," Stefoski said. "After a single intravenous dose, the patients could walk better and see better."

Rush was granted market exclusivity by the FDA under the Orphan Drug Act of 1983 and licensed worldwide rights for dalfampridine first to Ireland-based Elan Corporation and subsequently to Acorda Therapeutics, Inc., located in Hawthorne, New York. This month, Acorda began marketing dalfampridine in the U.S. under the brand name Ampyra.

In two Phase III clinical trials conducted by Acorda, the drug yielded a consistent improvement in walking speed. Walking speed increased by about 25 percent in 35 percent of patients in one trial and in 43 percent of patients in the other, as measured by a standard test called the Timed 25-Foot Walk. Study participants who took the drug also experienced greater leg strength than those who took a placebo.

Stefoski said that although the drug has been approved specifically for the treatment of impaired walking, it also relieves other symptoms of multiple sclerosis, since it restores signal conduction in all the affected nerve fibers.

Multiple sclerosis is a chronic, often disabling autoimmune disease. According to the National Multiple Sclerosis Society, more than 2.5 million people worldwide and 400,000 people in the U.S. have been diagnosed with the disease. Symptoms include, in addition to difficulty walking, but fatigue, lack of balance, and problems with eyesight and memory, and heat sensitivity.

Multiple sclerosis takes several forms. The relapsing remitting form, the most common, is characterized by unpredictable acute attacks followed by periods of months to years of remission, with no new signs of disease. In secondary progressive and primary progressive forms of the disease, there is a steady, permanent neurological decline with no periods of remission. Tests have shown that dalfampridine works for all forms of .

Explore further: FDA proposes accelerated medical device approval plan

add to favorites email to friend print save as pdf

Related Stories

Researchers welcome new multiple sclerosis drug

Jan 23, 2010

The Food and Drug Administration has approved the drug fampridine-SR for the treatment of multiple sclerosis. Researchers at the University of Rochester Medical Center (URMC) have been evaluating the effects of the drug ...

Drug improves mobility for some MS patients

Feb 27, 2009

The experimental drug fampridine (4-aminopyridine) improves walking ability in some individuals with multiple sclerosis (MS). That is the conclusion of a multi-center Phase 3 clinical trial, the results of which were published ...

Stem cell transplant reverses early-stage multiple sclerosis

Jan 30, 2009

Researchers from Northwestern University's Feinberg School of Medicine appear to have reversed the neurological dysfunction of early-stage multiple sclerosis patients by transplanting their own immune stem cells into their ...

Drug studied as possible treatment for spinal injuries

Nov 19, 2009

Researchers have shown how an experimental drug might restore the function of nerves damaged in spinal cord injuries by preventing short circuits caused when tiny "potassium channels" in the fibers are exposed.

Recommended for you

FDA proposes accelerated medical device approval plan

Apr 23, 2014

(HealthDay)—The U.S. Food and Drug Administration has proposed a new program that would provide expedited access to high-risk medical devices intended for patients with serious conditions whose medical ...

Targeting drugs to reduce side effects

Apr 23, 2014

(Medical Xpress)—Consider ice cream – the base of which is frozen cream. Ingredients are then added to make different flavours. All these flavours are distinctly different but are created from the same foundation.

User comments : 2

Adjust slider to filter visible comments by rank

Display comments: newest first

psommerfeld
not rated yet Apr 05, 2010
The drug was approved by the FDA as an orphan drug in 1983. Soooo ... what happened in the ensuing 15+ years??
deatopmg
1 / 5 (1) Apr 05, 2010
Since low dose naltrexone stops the progression of MS, combining it w/ dalfampridine might give these people a normal life span w/ a minimal symptoms.

@psommerfeld what do you think researchers were doing w/ 4-aminopyridine for the past 20 yrs?

More news stories

Genetic code of the deadly tsetse fly unraveled

Mining the genome of the disease-transmitting tsetse fly, researchers have revealed the genetic adaptions that allow it to have such unique biology and transmit disease to both humans and animals.

Ocean microbes display remarkable genetic diversity

The smallest, most abundant marine microbe, Prochlorococcus, is a photosynthetic bacteria species essential to the marine ecosystem. An estimated billion billion billion of the single-cell creatures live i ...