英文版原文
https://parkinsonsnewstoday.com/experimental-treatments/ads-5102-amantadine/
ADS-5102 (Amantadine)
parkinsonsnewstoday.com
ADS-5102 (amantadine) is a Parkinson’s disease treatment developed by Adamas Pharmaceuticals.
The company created the drug to reduce the dyskinesia, or involuntary movements, caused by another Parkinson’s treatment, levodopa. ADS-5102 is also aimed at reducing the time during the day when Parkinson’s symptoms return between doses of medication. U.S. regulators have yet to approve the therapy, which is in the clinical-trial stage.
How ADS-5102 works
The active component in ADS-5102 is amantadine hydrochloride. Amantadine is a glutamate antagonist, or molecule that inhibits the action of the neurotransmitter glutamate. Neurotransmitters send signals between brain cells.
One of the biological processes that glutamate plays a role in is movement. It passes signals from the brain to muscles by interacting with NMDA receptors on the outside of cells.
Continuous use of levodopa over a long period can lead to an increase in glutamate signaling, disrupting motor control messages. The result is a Parkinson’s patient experiencing involuntary movements.
ADS-5102 blocks glutamate’s access to the NMDA receptors. This reduces the level of signaling and therefore the level of involuntary movement.
Adamas formulated the drug for extended release, which means that its levels in the blood increase over time. By administering the treatment before bedtime, the levels gradually increase to their highest concentration during daytime, when Parkinson’s symptoms are usually strongest.
ADS-5102 in clinical trials
Adamas has published the results of a Phase 3 clinical trial (NCT02136914) assessing the effectiveness and safety of ADS-5102 tablets in Parkinson’s patients, compared with a placebo. The trial, EASE LID, was a 24-week, multi-center, randomized, double-blind, placebo-controlled study. The company published the results in the journal JAMA Neurology.
Participants treated with ADS-5102 experienced a significant decrease in involuntary movement, compared with those treated with a placebo. Researchers used the Unified Dyskinesia Rating Scale (UDysRS) to assess movement.
ADS-5102 also reduced by an hour the amount of time during the day when Parkinson’s symptoms returned, compared with a placebo.
Adamas Pharmaceuticals has conducted three other clinical trials of ADS-5102: EASED (NCT01397422), EASE LID2 (NCT02202551), and EASE LID 3 (NCT02274766).
EASE LID 2 is an ongoing, long-term open-label trial. Patients have received ADS-5102 for two years. The study is expected to wrap up in August 2017.
Adamas announced the results of EASE LID 3 recently. They confirmed that the therapy leads to a statistically significant reduction in levodopa-related dyskinesia in Parkinson’s patients.
The trials have demonstrated that ADS-5102 is safe and that patients tolerate it well. Common adverse effects that patients reported include visual or sound hallucinations, dry mouth, dizziness, insomnia, falls, constipation, nausea, decreased appetite, a blotchy-skin condition known as livedo reticularis, a swelling of extremities known as peripheral edema, and orthostatic hypotension, or low blood pressure when standing up from a sitting or lying position.
Other information
Adamas Pharmaceuticals submitted a New Drug Application for ADS-5102 to the U.S. Food and Drug Administration in October 2016. The agency has set August 24, 2017, as the day it will decide on the application.
Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
