MDA has awarded eight new grants totaling nearly $2.5 million to fund research projects focused on uncovering the causes of, and developing therapies for, ALS. The effective start date for the grants was Feb. 1, 2011.
At its December 2010 meeting, MDA's Board of Directors reviewed and approved 44 new grants covering some 20 neuromuscular diseases, including eight for ALS. Funding was based on recommendations from MDA's Scientific and Medical Advisory Committees, which considered the capabilities of the applicant, the scientific merit of the project and the proposal's relevance to developing treatments for the disease.
To learn more about these ALS grants, and the rest of the 44 grants approved in this latest funding cycle, see the Grants at a Glance slideshow, or the Quest News Online article MDA Awards $13.5 Million in Research Grants.
To see all of the more 330 research grants currently being funded by MDA, view this PDF.
Highlights of new grants
Motor nerve terminals:
Ellen Barrett, professor of physiology and biophysics at the University of Miami (Florida) Miller School of Medicine, received $297,102. Barrett is studying the dependence of motor nerve terminals (the part of the motor neuron, or nerve cell, that conveys signals from the brain to muscles) on the "energy factories" that power cells, called mitochondria.
Results from Barrett's work may reveal potential for a combination of treatments aimed at preserving both motor neuron terminals and cell bodies to effectively slow ALS disease progression.
Phase 2 human clinical trial:
Research fellow James Berry at Massachusetts General Hospital in Boston, was awarded $180,000. Berry is a member of the study team currently planning a phase 2 clinical trial in people with familial ALS of the experimental drug ISIS-SOD1-Rx, made by Isis Pharmaceuticals of Carlsbad, Calif. The trial is planned as a follow-on study to a phase 1 trial of the drug that’s currently under way.
Results from Berry's work could lead to a phase 3 clinical trial of ISIS-SOD1-Rx in people with familial ALS.
3-D model of the human spinal cord:
MDA awarded $347,094 to François Berthod, a professor in the department of surgery at Laval University in Quebec City, Quebec, Canada. Berthod is developing a three-dimensional model of the human spinal cord using nervous system cells obtained from the tissues of people with ALS.
Findings from Berthod’s work are expected to improve understanding of the causes and progression of sporadic (noninherited) ALS.
MDA awarded $180,000 to Adrian Israelson, a postdoctoral researcher at the University of California, San Diego in La Jolla. Israelson will focus on the ways in which mutant misfolded SOD1 protein (associated with some forms of ALS) associates with mitochondria, and whether and how those interactions affect mitochondrial function, possibly leading to motor neuron death.
Israelson’s findings may provide valuable insight needed for development of therapies that either prevent or slow the degenerative process in the disease.
Changes in mitochondria:
MDA awarded $350,133 to Michael Miller, associate professor in the department of biology at the University of Alabama, Birmingham. Miller will study the ways in which gene mutations in familial ALS may disrupt a signaling mechanism necessary for mitochondrial function and, in turn, affect motor neuron health.
Findings from Miller's work may point to a mechanism responsible for motor neuron death in ALS.
New iPSC research model:
Alysson Muotri, assistant professor at the University of California, San Diego in La Jolla, was awarded $362,466 to support his development of a new ALS research model. The model will be made using sophisticated induced pluripotent stem cell (iPSC) technology that will allow the scientists to use the genomes (DNA) of ALS-affected individuals to generate a stem cell line. Isolated populations of neural cells can then be matured from this line and isolated for study.
It’s hoped the new model also will help make diagnosis easier with early-diagnostic tools, and inspire new therapeutic strategies.
Motor neuron development:
Shanthini Sockanathan, associate professor of neuroscience at Johns Hopkins School of Medicine in Baltimore, received $396,000 to study motor neuron development in ALS. Sockanathan and colleagues will use a combination of approaches to focus on the mechanisms underlying regulation, initiation, extent and rate of motor neuron differentiation (maturation).
Results from Sockanathan’s work could provide biological targets at which to aim future therapeutic strategies for ALS.
MDA awarded $330,000 to Jiou Wang, assistant professor of biochemistry & molecular biology and neuroscience at Johns Hopkins University in Baltimore, to support comparison of two types of familial ALS — those associated with the SOD1 protein and those mediated by another protein, TDP43. The investigators will examine the molecular mechanisms underlying the toxicity triggered by flawed SOD1 and TDP43 genes in a nematode (worm) research model of ALS.
It’s hoped in-depth analysis of these mechanisms will reveal pathways at which researchers can target effective therapeutics.
Editor's note: This article was updated Feb. 11, 2011, to reflect that ISIS-333611 is now called ISIS-SOD1-Rx.