The Amyotrophic Lateral Sclerosis (ALS) Association is funding a major clinical trial to determine if lithium can slow disease progression in patients in the early stages of ALS. The study builds on earlier promising results from preclinical research and a small, open-label investigation in patients with ALS. ALS is a progressive, neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. When the motor neurons die, the ability of the brain to initiate and control muscle movement is lost, leading to progressive paralysis.

The trial is being supported through the association's TREAT ALS (Translational Research Advancing Therapies for ALS) initiative and will use the TREAT ALS/NEALS Clinical Trials Network. Lead investigators for the study are Merit Cudkowicz,MD, and Swati Aggarwal, MD, from Massachusetts General Hospital; Lorne Zinman, MD, from the University of Toronto; Petra Kaufman, MD, from Columbia University; and Jeremy Shefner, MD, from SUNY Upstate Medical University. In addition to the association, funding partners for the new study include the National Institute of Health/National Institute of Neurologic Diseases and Stroke and the ALS Society of Canada. Investigators worked together with the funding agencies to design the most appropriate study within the shortest possible time frame.

Lithium is a simple chemical substance approved for use in human beings that is prescribed as a mood stabilizer. Lithium protects neurons in the brain in animal models of neurodegenerative diseases, including Alzheimer's disease and Parkinson disease. It recently was shown to do the same in a mouse model of ALS. In that study, lithium prolonged survival and protected cells in both the brain and spinal cord. Although the exact mechanism of lithium's effect is unknown, researchers have proposed that it promotes clearance of toxic protein accumulation.

A study in a small number of patients with ALS compared lithium plus riluzole (an approved treatment for ALS) to riluzole alone. After 15 months, no deaths occurred in the 16 participants treated with lithium plus riluzole, whereas 29% of patients taking riluzole alone had died. Patients on lithium also had a markedly lower decline in disease-related disability. However, the trial was limited by the small numbers of patients and the absence of a placebo treatment. Both the patient and the doctor knew whether the patient was taking lithium, which may have influenced the response to treatment or interpretation of disability. Because of diagnostic and prognostic variability in persons showing symptoms of ALS, the small numbers in this study were not sufficient to know whether lithium was an effective treatment. Many apparently effective treatments in open trials (trials lacking a concurrent placebo group) fail in larger double-blind trials, in which neither the physician nor the patient knows whether the patient is receiving the study drug.

The new trial will be a double-blind, placebo-controlled trial with 84 patients, who will be randomized to either lithium or placebo. A review of data will occur after the 84th person is enrolled, and then a decision will be made on whether to expand to 250 patients. Patients may be included if they are within 3 years of their diagnosis and are not already taking lithium. Treatment will last for up to 1 year. The disease course and safety assessments will be measured at regular intervals over that time. Further details, including trial sites, enrollment criteria, and start dates, will follow shortly.

The ALS Association is the only national, not-for-profit voluntary health organization devoted solely to fighting ALS through research, patient services, advocacy, and public education and information. TREAT ALS is a drug discovery program and clinical trials process created by the association that accelerates discovery and testing of clinical candidates.