OPEN LABEL EXTENSION OF PROTOCOL AALS-001 (AALS-001-OL)

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: The primary objective of this study is to assess the long term safety and tolerability of Arimoclomol in patients with ALS who completed 12 weeks of treatment and the Week 16 follow-up Visit of the AALS-001 study. The secondary objective is to obtain long-term data on ALSFRS-R and vital capacity. RESEARCH PLAN: Arimoclomol is a small molecule that up-regulates heat shock proteins in cells under stress. When given both pre-symptomatically and at disease onset in a mutant superoxide dismutase transgenic mouse model of ALS, Arimoclomol extends survival by five weeks. Arimoclomol delays the death of motor neurons in treated mice and delays the associated loss of motor unit potentials. The effect of Arimoclomol is greater than that found with most other compounds, including Riluzole and Minocycline, when tested in the vivo model of ALS. METHODS: This study is an open-label extension of AALS-001 in those patients who completed 12 weeks of treatment and the week 16 follow-up visit of the AALS-001 study will receive Arimoclomol at 100 mg TID for approximately 6 months. Visits will occur at screening, baseline, and once a month for six months (total of 8 visits) The safety of Arimoclomol will be evaluated using vital signs and weight, clinical laboratory determinations, EKG, physical and neurological examinations, and reporting of adverse events. Of particular interest would be adverse experiences that would not be tolerable in a drug that might have to be administered life long. Given the severity of the disease, fairly severe side effects might be tolerated. CLINICAL RELEVANCE: ALS is a severe and ultimately fatal disease, for which there is no known effective treatment. Any compound proven to slow the course of the illness will be of immediate importance clinically; moreover, a positive outcome will enhance our understanding of the underlying biology of ALS. Should Arimoclomol show preliminary tolerability, safety and CNS penetration in patients with ALS, the data from the study would then be used to support an efficacy study in ALS.