July 6, 2006

The ALS Association Funds Investigation of Cell Targets of ALS

 
Roberta Friedman, Ph.D., Research Department Information Coordinator, The ALS Association

Mice can be engineered to make the mutated protein linked to some inherited forms of ALS in only certain cells of the nervous system. The ALS Association is funding a new project to find out exactly which of the cells are crucial to the development and progress of the disease.

By clarifying the role of each cell in the nervous system in producing amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease), researchers led by Raymond Roos, M.D., of the University of Chicago, are paving the way to a therapeutic approach in which drugs might be targeted to specific cells and the processes they mediate.

This new project, funded through The ALS Association’s program to recruit and retain experts in critical areas relevant to ALS, builds on important findings funded by The Association on cell roles in ALS. Work by Don Cleveland, Ph.D., and colleagues at the Ludwig Institute at the University of California, San Diego, showed that the immune cells of the nervous system, called microglia, are important to the disease process in ALS. If microglia do not make the mutant protein, copper-zinc superoxide dismutase (SOD1), the later stage of the mouse counterpart of the disease is prolonged.

The Roos project will examine in detail which cells of the nervous system are critical to the start and progression of ALS. Mice will be bred to express the mutant gene in just the neurons of the spinal cord or just the supporting, surrounding cells. The health and any symptoms of these mice will be compared.

Importantly, mice are now available in which the gene for mutant SOD1 can be switched off. Will mice recover when production of the mutant SOD1 is stopped? At what stage of disease can progression of cell death be stopped and can damage be reversed?

The planned studies by Roos and colleagues could help show why motor neurons die in inherited ALS linked to mutant SOD1. There might be a final common path to motor neuron death, so these studies could reveal a disease process common to all ALS.  As a result, new directions for treatment may be revealed that would help all patients with ALS.

For further information about the roles of different cell types in ALS, click here.