August 1, 2006
Research Update — from ALSA’s National Office
The ALS Association Funds Searches for New Gene Links to ALS
Roberta Friedman, Ph.D., ALSA Research Department Information Coordinator
The ALS Association is pleased to provide funding to two gene finding projects as part of its efforts to recruit and retain established investigators in the search for therapeutic targets for amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease). These projects will help uncover the potentially common process that kills the motor neurons in the disease.
One project in partnership with the Motor Neurone Disease Association will be an effort led by Jackie de Belleroche, M.D., Ph.D., Imperial College London, who will create a transgenic mouse based on a new mutation identified in a family with inherited ALS. This gene change on chromosome 12 affects a protein that removes potentially toxic molecules. Mice that reflect any motor neuron defects of this gene change would contribute to efforts to explain the disease and give clues to the basic biology behind ALS. The protein that is mutated, called D-amino acid oxidase (DAO), helps keep in check the potentially toxic messenger molecule, glutamate. The investigators will use cell cultures as well as the new mice expressing the mutated human gene in order to clarify the potential role of DAO and glutamate in ALS.
Another Association-initiated grant goes to Ammar Al-Chalabi, Ph.D., at the Institute of Psychiatry, King's College, London. Al-Chalabi’s team is seeking genes that increase susceptibility to developing ALS, even in people without a family history. Usually such searches are carried out with suspected genes in mind. Instead, Al-Chalabi and his collaborators are working independent of any assumptions to avoid missing any possible candidate locations for genes involved in ALS. They are using normal variations in the human genes that can serve as signposts for blocks of genes on the chromosomes that might have differences that are more common in people with ALS. Only those regions identified as containing a variation are searched further for a specific gene change. Their search has come up with a short list of the most likely regions on chromosomes linked to ALS liability that they will now examine in detail to confirm the association.
Together these projects should uncover new genes that can produce motor neuron disease. Such genes could provide targets at which to aim therapeutic innovation for ALS patients.
