In the June 15 issue of the Journal of Neuroscience, Robert Ferrante, Flint Beal and associates describe experiments in which they added creatine supplement to the feed of mice expressing part of the human Huntington's gene. These mice typically show physiological and behavioral signs resembling human Huntington's at an early age. In the mice fed creatine, there was significant protective effect by a number of measures, e.g., increased length of survival, decreased overall brain atrophy and body weight loss, delayed atrophy of striatal neurons, delayed formation of aggregates of the gene product huntingtin, and improved motor performance.

The idea behind using creatine in Huntington's, as well as other neurodegenerative diseases, is that these disorders may interfere with energy metabolism and thereby initiate apoptotic mechanisms. Creatine, in the form creatine phosphate, functions like ATP, storing high-energy phosphate bonds. It has been suggested that supplemental creatine can thus help buffer against energy metabolism perturbations caused by neurodegenerative disease processes, including those caused by Alzheimer's.-Hakon Heimer.

Comment by Ethan Signer-Cure HD Initiative
This latest in a series of studies on creatine from the Beal group demonstrates a benefit in a transgenic mouse model of Huntington's disease (HD), similar to that seen in their earlier work with a transgenic mouse model of amyotrophic lateral sclerosis (ALS) and pharmacological mouse models of HD and Parkinson's disease (PD). The benefit is substantial if modest, including improvement in a variety of behavioral and metabolic markers as well as a 20 percent increase in survival, although the inverted dose-response curve remains puzzling. The extent of the benefit and its effect on neurodegenerative diseases as different genetically as HD, ALS and PD presumably reflect mitigation of compromised energy metabolism that is secondary to the primary gene defect, and therefore suggest creatine could benefit other neurodegenerative diseases (such as Alzheimer's disease?) as well. Although a definitive trial of creatine in HD itself has yet to be carried out, it is significant that creatine is considered completely safe for humans and is widely available over the counter without prescription.

Ethan R. Signer
Professor of Biology Emeritus, MIT
Executive Director, Cure HD Initiative, Hereditary Disease Foundation
230 Park Avenue, 7th floor
New York, NY 10169
tel 917/368-5498 fax 917/368-5499
signer@mit.edu


Reference:Ferrante RJ, Andreassen OA, Jenkins BG, Dedeoglu A, Kuemmerle S, Kubilus JK, Kaddurah-Daouk R, Hersch SM, Beal MF. Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. J Neurosci 2000 Jun 15;20(12). Abstract