The study was designed as a single-center, open-label, single-arm pilot study to estimate the safety and efficacy L-carnitine in ALS patients with CHCHD10 mutations.

The study was designed as a single-center, open-label, single-arm pilot study and was performed at the ALS inpatient clinic of the Xuanwu Hospital in Beijing, China. ALS patients with CHCHD10 mutations were recruited to participate in the clinical trial. The patients were given L-carnitine therapy administered every 8 weeks, consisting of 1g L-carnitine diluted in 500 mL of 0.9% sodium chloride solution via intravenous infusion once daily. Each treatment cycle lasted 2 weeks, repeated at 8-week intervals for a total of 3 cycles, with L-carnitine 1g is administered orally once daily during the intervals between intravenous therapies. Primary end point was the changes of ALS-FRS-R scores, and secondary end points were the changes of plasm NfL level, FVC%, weight and ALSAQ-40 scores. Eligible patients were assessed at baseline and after 2, 10, 12, 20 and 30 weeks. At each visit, a detailed neurological examination, including assessment of general nerve function as well as quantitative and qualitative evaluation of the motor system, were performed for the patients. All adverse events (AEs) encountered and any serious events were to be recorded as true. Severity was graded according to the modified WHO criteria for toxicity (http://www.regsource. com/_Adverse_Event_Reporting/_adverse_event_ reporting.html) where applicable.

Inclusion Criteria:

• Male or female, 18-80 years old
• ALS diagnosed as definite or probable as defined by the World Federation of Neurology revised El Escorial criteria
• Carrying pathogenic CHCHD10 mutations
• Capable of providing informed consent and following trial procedures
• Forced Vital Capacity (FVC) >40% of predicted value for gender, height, and age at the Screening Visit
• Subjects develop at less moderate degree of motor dysfunction, with ALS-FRS-R total scores less than 46
• Both male and female patients must agree to use adequate birth control for the whole duration of the study within 30 weeks
• Subjects are willing and expected to complete the 30-week follow up, including 3 times hospitalization.

Exclusion Criteria:

• Presence of tracheostomy
• History of known allergy to L-carnitine
• Abnormal liver function defined as AST and/or ALT > 3 times the upper limit of the normal
• Renal insufficiency as defined by eGFR < 60 mL/min/1.73m2
• Pregnant women or women currently breastfeeding
• Clinically significant unstable medical condition (other than ALS) that would pose a risk to the subject if they were to participate in the study
• Anything that, in the opinion of the Site Investigator, would place the subject at increased risk or preclude the subject's full compliance with or completion of the study.