Twelve new grants totaling $3.6 million have been awarded in support of research studies that will explore the causes of, and potential treatments for, amyotrophic lateral sclerosis (ALS).
“This is truly an exciting time in ALS research,” Jane Larkindale, MDA vice president of research, said about the new grants, which took effect Feb. 1. She noted that recent discoveries of new disease-causing genes for ALS have opened new avenues for research into the causes of the disease and potential treatments. "We cannot cure a disease when we don’t know the cause, but we now have so many more pieces of the puzzle on the table that a treatment is looking possible. Projects like these will bring us closer," she said.
To see details on each of these new MDA grants, visit the Winter 2013 Grants at a Glance slideshow.
Perhaps the most significant discoveries about ALS in recent years have involved the identification of genes that cause the disease. The single most common genetic cause is a mutation in a gene called C9ORF72. Jeffrey Rothstein, professor of neurology and neuroscience at Johns Hopkins University in Baltimore, has received MDA funding to develop new cellular models to study the effects of this gene mutation. He will use patient skin cells to create induced pluripotent stem cells, or iPS cells, which can be transformed into motor neurons (the muscle-controlling nerve cells that are lost in ALS) for study in the lab.
Rothstein hopes to find a molecular signature for the disease-causing effects of the mutant C9ORF72 gene. That signature, or biomarker, can then be used to quickly assess the effects of potential therapies on the same cells. “The use of these human cells may allow us to efficiently and quickly develop a drug therapy for the C9ORF72 form of ALS,” he says.
Two other ALS-associated genes, TDP43 and FUS, are also being studied intensively for the clues they may provide. Both genes encode proteins that handle an information molecule in the cell called RNA. Increasing evidence points to defects in RNA handling as a central part of the ALS disease process.
Heather Durham, professor at the Montreal Neurological Institute of McGill University in Quebec, Canada, will study the consequences for motor neurons of mutations in the FUS gene, which she thinks include problems in responding to the level of neuronal activity and stress.
Fenghua Hu, research scientist at Cornell University in Ithaca, N.Y., will study the effects of TDP43 mutation. While the gene mutation is a rare cause of ALS, Hu notes that even in people with ALS who do not have TDP43 mutations, the TDP43 protein often clumps together abnormally, forming aggregates within motor neurons. This phenomenon, Hu notes, “suggests that the misbehavior of TDP43 protein could cause neurodegeneration.” Hu's study of a potential relationship between the protein and neurodegeneration should help researchers develop better targets for therapy in ALS.
Several new projects will explore treatment strategies:
Sunitha Rangaraju, a postdoctoral research scientist at the Scripps Research Institute in La Jolla, Calif., will test whether compounds that extend the life span of healthy roundworms also can extend life in a worm model of ALS. Studies in roundworms offer scientists the ability to screen many thousands of compounds quickly and to rapidly test the effects of the most promising drug candidates.
A gene that, when mutated, can cause some instances of ALS also is responsible for some instances of another neuromuscular disease, inclusion-body myositis (IBM). The gene, called valosin-containing protein (VCP), helps clear misfolded proteins so that they don’t cause damage within cells. Mutations in VCP lead to protein aggregates within neurons (in ALS) and muscle (in IBM). Three groups of researchers are exploring the overlap of these two diseases and the role of protein aggregation in them:
To see details on each of these grants, visit the Winter 2013 Grants at a Glance slideshow.
Richard Robinson is a freelance medical and science writer based in Sherborn, Mass.
|Update (Feb. 5, 2013):Information about MDA’s grant to Sunitha Rangaraju, which had been inadvertently omitted, was added to this article.|