From Wasp Fungus to New MS Drug

800px-wasp_080427Just twenty years ago, there were no therapies available for the management of multiple sclerosis. Physicians could give patients drugs to try and blunt the damage caused by the disease’s intermittent attacks on the central nervous system, but no therapies had been proven effective at preventing those attacks. That changed in the mid-90’s, when successful studies and clinical trials led to the approval of interferon therapies, immune system modulators that block the autoimmune response responsible for MS attacks.

Interferon therapies have since multiplied, and other MS treatments have come to market. But each of these approaches have side effects, must be delivered by injections, and don’t work in every patient. Today, the FDA approved a sixth MS therapy, called fingolimod – the first protection against MS attacks available as a pill. Experts welcomed the decision, saying it would give neurologists a valuable new weapon in the fight against multiple sclerosis.

“This is the first pill for multiple sclerosis,” said Anthony Reder, MD, professor of neurology at the University of Chicago Medical Center. “We have six drugs right now, and they all involve injections. So the convenience alone of a pill is a major change in how we treat MS. It also expands the drugs available to treat MS, and may get some people who can’t take the other medicines. It will be used to replace drugs that are failing and possibly for new starts in some people.”

Fingolimod, code-named FTY-720 in trials and soon to be released by drug company Novartis as Gilenya, took a strange route to the clinic. The drug is based on a type of fungus, originally discovered in the intestines of wasps by Japanese researchers. Observing that the fungus secreted a chemical with the natural ability to suppress immune responses, scientists refined the chemical into a drug intended for use in people receiving transplanted organs. The eventual clinical trials for that use failed, but a secondary use presented itself: neutralizing the immune system attacks in multiple sclerosis patients.

This time around, the clinical data was much more successful. The results of two large Phase III clinical trials published in the New England Journal of Medicine in February showed exciting effects – a roughly 50 percent decrease in attacks in patients treated with fingolimod relative to patients receiving placebo or interferon therapy. MRI images also showed that fingolimod-treated subjects had fewer brain lesions, signs of progressive, permanent damage caused by MS attacks. Some side effects were observed, such as a transient decrease in heart rate after the first dose and a slight uptick in the number of infections, and experts said those will need to be monitored as the drug reaches a wide population.

“As always with these drugs, the people in study were a restricted group of patients with no cardiac disease, no diabetes, no pulmonary abnormalities,” Reder said. “When we go out into the real world, we have to be more conscious of potential side effects and interactions with other conditions.”

While fingolimod will immediately become an exciting new option for the most common form of MS, called relapsing-remitting, it has also shown hints of potential for another form of the disease, primary-progressive MS. Patients with progressive disease show a steady decline in neurological function rather than the intermittent attacks of relapsing-remitting MS patients, and no therapy has been found to help slow the process.

But laboratory studies using cell cultures and animal models have found that fingolimod may do more than just protect neurons from damage, it may repair them too. Collaborations between the research groups of Betty Soliven, associate professor of neurology at the University of Chicago, and Jack Antel of McGill University have produced evidence that fingolimod stimulates remyelination – replacing the neuronal coating that an MS attack destroys.

That repair function could contribute to fingolimod’s success in relapsing-remitting patients, and could make it a valuable weapon in the primary-progressive form of the disease as well. A new clinical trial funded by Novartis is under way in primary-progressive MS patients, Reder said, with the University of Chicago one of the trial sites. Other future studies may seek to find the lowest effective dose of fingolimod (thus minimizing its side effects) or look at whether a combination of the new drug with older treatments such as interferons is even more beneficial to MS patients. The longer menu of options can be confusing, but reflects a vast improvement for patients with a disease that is becoming managed with the right help.

“MS therapies are getting very complex,” Reder said. “To do justice to all of the effective drugs out there you need to talk to someone who has expertise with all of these therapies. It’s getting to the point where only very high level medical centers or sophisiticated neurology groups can handle these drugs. It’s turning into a neuroimmunology speciality, and we can handle it.”

About Rob Mitchum (526 Articles)

Rob Mitchum is communications manager at the Computation Institute, a joint initiative between The University of Chicago and Argonne National Laboratory.

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