Amantadine is a treatment for Parkinson’s disease that can also be used to treat fatigue in patients with multiple sclerosis (MS). Many generic formulations of amantadine are available. An extended release formulation (ADS-5102/Gocovri) is currently being developed by Adamas Pharmaceuticals.
How amantadine works
MS is a disease caused by the immune system mistakenly attacking the myelin sheath or the fatty coating that protects nerve fibers, and increases the speed of electrical signals that travel along them. The attacks cause damage to the nerve fibers, leading to neurodegeneration, which is responsible for the symptoms of MS.
Fatigue is a common MS symptom, occurring in more than 80 percent of cases. Fatigue management plans can help patients learn how to make behavioral changes and develop strategies to improve their lives. Therapies such as amantadine can also aid in combating fatigue.
How amantadine reduces fatigue in MS patients is not fully understood but it is thought that the treatment acts on the brain by increasing the release of a neurotransmitter or cell-signaling molecule called dopamine, and boosting the brain’s response to another neurotransmitter called norepinephrine.
Both dopamine and norepinephrine control how sensitive the brain is to nerve signals. Therefore, it’s possible that the combination of more dopamine and a stronger response to norepinephrine is responsible for the decrease in fatigue that’s experienced by some MS patients who use amantadine.
Amantadine may also act on the glutamate receptors of the brain, which are sometimes called the glutamate N-methyl-D-aspartate or NMDA receptors. Overactive NMDA receptors may contribute to some of the symptoms of MS, and research has focused on the potential therapeutic effect of reducing the activity of these receptors. Amantadine may bind to NMDA receptors and reduce their activity.
Amantadine in clinical trials for MS
A Phase 2 clinical trial (NCT02471222) to study the safety and efficacy of ADS-5102 to treat MS patients with fatigue showed it was well-tolerated. Patients improved their walking speed in a timed 25-foot walking test, which measures the time it takes for patients to walk a distance of 25 feet.
A Phase 3 ongoing clinical trial (NCT03185065) is testing the effects of commonly used medications to treat fatigue in MS. It enrolled 140 participants who were randomly divided into four groups and treated with either ADS-5102, modafinil, methylphenidate, or a placebo.
A Phase 3 clinical trial (NCT03436199) is currently recruiting MS patients with fatigue for a multicenter placebo-controlled trial in states across the U.S. A total of 540 patients are expected to enroll, and will be randomly assigned to receive either a placebo, 137 mg of ADS-5102, or 274 mg of ADS-5102 once daily at bedtime for 12 weeks. Fatigue will be assessed at the beginning and end of the trial using a timed 25-foot walking test.
An open-label extension study (NCT03567057) of the above trial is also planned in Colorado, Connecticut, Georgia, New York, and Washington. Patients will receive ADS-5102 once per day at bedtime for 52 weeks. Safety and tolerability are the primary goal measures, but patients will also be asked to complete a timed 25-foot walking test at four, 12, 24, and 52 weeks of the study to evaluate the efficacy of treatment.
Amantadine can cause side effects such as bladder pain, blurred vision, confusion, dizziness, fainting, falls, swelling of the hands and feet, and pain in the lower back or side.
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