National Institute of Neurological Disorders and Stroke (NINDS)
Background: Amyotrophic lateral sclerosis (ALS) is a disorder that damages nerve cells in the brain and spinal cord. It can cause muscle weakness, paralysis, and loss of movement. The symptoms grow worse over time. Half of all people with ALS live only 3 to 5 years after diagnosis. Current drug treatments can slow the progress of the disease, but they cannot stop or reverse it. Objective: To test a study drug (acamprosate) in people with ALS with a mutation in the C9orf72 gene. Eligibility: People aged 18 years and older with ALS. They must have a mutation in the C9orf72 gene. Design: Participants will have 13 visits over 32 weeks. Five visits will be at the clinic, and 8 visits will be by phone. Participants will have a baseline visit of up to 3 days. They will have a physical exam with blood tests. They will have imaging scans and tests of their breathing ability. Their memory, thinking, and behavior will be assessed. They will have a neurologic exam to check their reflexes, strength, balance, eyes, and coordination. They will complete questionnaires about their daily life. They will have a lumbar puncture to collect fluid from the area around the spinal cord. Acamprosate is a pill taken by mouth. Participants will take 2 pills by mouth 3 times a day with meals for 24 weeks. They will record their doses and any missed doses in a diary. Baseline tests will be repeated during follow-up clinic visits. These tests may be spread out over 3 days. During phone visits, participants will talk about how they are doing. They will review their diary with researchers.
Study Description: This study will evaluate the safety and clinical effects of acamprosate in patients diagnosed with amyotrophic lateral sclerosis who have a hexanucleotide repeat expansion in the C9orf72 gene. A drug repurposing evaluation using genomic data from C9orf72 genetic mutation carriers showed that acamprosate may have a neuroprotective effect in this group of patients in silico and experiments. To examine the in vitro effect, iPSC derived motor neurons from ALS patients with C9orf72 repeat expansion were treated with acamprosate and reduced cell death was observed. Exploratory en…
* INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following inclusion criteria: 1. Aged 18 years or older at the time of the screening visit. 2. Able to provide informed consent and comply with study procedures and availability for the duration of the study. If a participant lacks capacity to give consent, a Legally Authorized Representative (LAR) will be authorized to give consent on behalf of the individual. 3. Diagnosis of ALS (possible, probable, or definite according to the World Federation of Neurology El Escorial revised cri…
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