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 criteria or the Gold Coast Criteria) with or without mild cognitive impairment, mild behavioral impairment, or frontotemporal dementia (FTD).
4. CLIA-certified genetic testing showing a pathogenic hexanucleotide repeat expansion in the C9orf72 gene.
5. Symptom duration less than 2 years, or if greater than 2 years, disease progression at a rate that, in the judgement of the investigator, would allow for completion of the study.
6. If taking riluzole, edaravone, or phenylbutyrate/TUDCA, the participant must be on a stable dose for at least 30 days prior to the screening visit, or have stopped taking riluzole, edaravone, or phenylbutyrate/TUDCA at least 30 days prior to the baseline visit.
7. Participant must be competent to self-administer the medication as deemed by study team. Alternatively, participant must have a competent caregiver who can and will be responsible for administering the study drug. If there is no caregiver, another qualified individual must be available to administer the study drug.
8. Participant has established care with a neurologist and will maintain this clinical care throughout the study.
9. For females of reproductive potential: use of effective or highly effective contraception for at least one month prior to screening and agreement to use such a method during study participation and for an additional 8 weeks after the end of acamprosate administration. Participants of childbearing potential must have a negative pregnancy test at screening.
10. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation in this study:
1. Dependence on daytime mechanical ventilation (invasive or non-invasive, including Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP) at the time of the screening visit.
2. Participation in any other investigational drug trial or using investigational drug(s) (within 4 weeks prior to the Day 0 visit and thereafter).
3. Participants must not become pregnant or breastfeed for the duration of the study. Participants of childbearing potential must have a negative pregnancy test at screening and be non-lactating.
4. Men who are trying to become fathers or donate sperm.
5. History of positive test or positive result at screening for HIV.
6. History of severe sulfite allergy (i.e., anaphylaxis).
7. Presence of any of the following clinical conditions at the time of screening:
1. Active drug abuse or alcoholism.
2. Unstable medical condition that, in the opinion of the investigators, makes participation unsafe.
3. Renal impairment estimated glomerular filtration rate <=60mL/min/1.73m\^2.
4. Unstable psychiatric illness defined as psychosis or untreated major depression within 90 days of the screening visit.
8. Safety Laboratory Criteria at the screening visit:
1. Estimated glomerular filtration rate <=60mL/min/1.73m\^2.
2. Platelet concentration of <100,000/microl.
3. PT and PTT >1.2 times the upper limit of normal.
4. Hemoglobin <10mg/dL.
5. Positive Hepatitis B Surface Antigen and Hepatitis C Virus Antibody
9. Participants who are unable to swallow tablets whole, as required by the administration guidelines. This includes individuals with any medical condition or physical limitation that impedes their ability to swallow solid dosage forms.
10. Participants who are dependent on a gastrostomy tube for medication administration. Since acamprosate is in tablet form that cannot be crushed or altered, it is unsuitable for administration through a gastrostomy tube.