The ALS Association in the US and the ALS Society of Canada are among the funding partners for a clinical trial in North America that will attempt to build on promising indications from preclinical research and a small, open-label human study that the standard mood stabiliser lithium co
uld slow disease progression in Amyotrophic Lateral Sclerosis (ALS).
The next step is a double-blind, placebo-controlled trial with 84 early-stage ALS patients at sites in the US and Canada, who will be randomised to either lithium or placebo. Once the 84th patient has been enrolled, a decis
ion will be taken on whether to expand the trial to 250 patients. The treatment will last for up to one year, with regular safety assessments and measurements of disease course over that time. Eligible patients will be within three years of their diagnosis and will not already be taking lithium.
The ALS Association, based in Calabasas Hills, California, will support the trial through its TREAT ALS (Transitional Research Advancing Therapies for ALS) initiative, using the TREAT ALS/NEALS Clinical Trials Network. NEALS is the North East ALS Consortium, a group of US academic investigators with extensive experience in ALS clinical trials that was set up in 1995. The Consortium formed a partnership with the ALS Association in June 2007 to provide a network of clinical investigators ready to test promising compounds in patients with the disease.
An addition to the Association and the ALS Society of Canada, the funding partners for the new study include the US National Institutes of Health/National Institute of Neurological Diseases and Stroke.
Also known as Lou Gehrig’s disease, ALS is a progressive neurodegenerative condition that affects nerve cells in the brain and spinal cord, usually with fatal consequences. In animal models of neurodegenerative diseases, including Alzheimer’s and Parkinson’s, lithium has been shown to protect neurons in the brain. More recently, the ALS Association noted, the same effect has been demonstrated in a mouse model of ALS, in which lithium prolonged survival and protected cells in both the brain and spinal cord.
In February 2008 an Italian team led by Francesco Fornai from the Department of Human Morphology and Applied Biology at the University of Pisa published the results of a small parallel-group, randomised study of lithium in ALS in the US journal, Proceedings of the National Academy of Sciences. Out of 44 adults with ALS, 16 were randomised to the approved ALS treatment, riluzole (Rilutek), plus lithium, and the remainder to riluzole alone.
As the ALS Association pointed out after 15 months no deaths had occurred in the 16 patients treated with riluzole plus lithium, whereas 29% of the riluzole-only group had died. Disease-related disability was also markedly less pronounced in the riluzole-lithium patients. Nonetheless, the Association cautioned, the trial was limited by the small number of patients, which could not account sufficiently for the diagnostic and prognostic variability in people with symptoms of ALS, and by the lack of a placebo control.
