MS-related Nerve Damage May Be Treatable with Anti-Seizure Drug

Patricia Silva, PhD avatar

by Patricia Silva, PhD |

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phenytoin and optic neuritis

Researchers from the University College London (UCL) found that the anti-convulsant drug phenytoin protected neural tissue in patients with optic neuritis — often the first symptom of multiple sclerosis (MS) — a condition that causes the nerves carrying information between the eyes and the brain to become inflamed and progressively damaged.

The study — led by Dr. Raju Kapoor at the UCL Institute of Neurology with the collaboration of MS societies in both the U.K. and U.S. — investigated a repurposing of an existing treatment with known clinical safety and efficacy, and one that, researchers and others said, showed considerable promise in protecting both optical and central nervous system nerve cells from damage during MS attacks.

“The Society made a strategic investment to encourage research in the area of neuroprotection as an approach to preventing progressive disability in people with MS,” Dr. Bruce Bebo, executive vice president for research at the National MS Society, said in a news release. “An intriguing aspect of this study is that it involved repurposing a therapy already on the market, an approach that could cut years of development time and speed the use of medications for a new indication such as MS.”

Research findings,  presented at the American Academy of Neurology 67th Annual Meeting, were recently published in the journal The Lancet Neurology in the article “Phenytoin for neuroprotection in patients with acute optic neuritis: a randomised, placebo-controlled, phase 2 trial.

Eighty-six MS patients with acute optic neuritis were enrolled in the double-blind Phase 2 study and randomly assigned to  receive either phenytoin (Dilantin) or a placebo for three months. Optical Coherence Tomography (OCT) was used to assess the thickness of the retina and the light-sensitive nerve layer at the back of patients’ eyes. Trial results found that patients treated with phenytoin had 30 percent less overall damage to the nerve fiber layer than patients receiving placebo.

“This is great news for people with MS and we’re very proud to have co-funded this trial,” said Dr. Emma Gray, head of clinical trials at the MS Society. “They also suggest that the same treatment may work in other situations where neurodegeneration leads to disability. There are currently no treatments that can directly protect the nerves from damage in MS and, if effective, this treatment could be beneficial for all types of the condition, which is currently unheard of.”

Dr. Gray added, “Our goal is to ensure all people with MS have access to effective treatments that can slow, stop or reverse the damage caused in MS. This trial brings us one step closer to that goal.”

The team had been investigating sodium channels as part of its research into neuroprotection when they found that, in inflammation, the axons of nerve cells become filled with sodium, leading to an influx of calcium that causes cell death. They then investigated ways in which sodium could be then prevented from entering into the cells.

“We wanted to find out if the theory that blocking sodium currents, which we developed in basic work over many years, actually served to protect neural tissue — a test-bed to see if we can achieve neuroprotection,” said Dr. Kapoor. “These are promising results and if our findings are confirmed by larger, phase 3 trials, could lead to a new treatment that protects nerves from the damage caused both in optic neuritis and throughout the central nervous system in other attacks of MS.”

Optic neuritis provided the researchers with a window into the study of active inflammation early on in disease development. “We have been trying to achieve neuroprotection ever since we realised that disability was due to nerve damage, so it is very encouraging that we have now found one way of doing so. We hope this will open the door to significant progress in preventing disability not only in optic neuritis, but also in MS as a whole,” Dr. Kapoor concluded.

MS is estimated to affect over 100,000 people in the U.K. alone, with symptoms tending to show in people between 20 and 30 years of age. MS damages the central nervous system, causing confused and delayed messages to be sent from the brain and spine to other parts of the body, and leading to chronic fatigue, pain and disability in patients.


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