ALS Association Research Grants Announced
New research grants by The ALS Association will support investigations of new disease models, pathogenesis of ALS, biomarkers of disease progression, and development of new treatments. The research portfolio supported by the Association is designed to speed therapy development by attacking ALS on all fronts, from basic research to clinical trials. Each year the Association funds the most promising research from hundreds of investigator-initiated proposals. In addition, it actively seeks researchers to undertake studies identified by the Association as critical for filling gaps in knowledge of ALS. The Association also gives the Milton Safenowitz post-doctoral fellowship award for ALS research to encourage young scientists to focus their research efforts on ALS.
Newly funded investigator-initiated research will study the following important questions:
Why do motor neurons die in ALS?
The cause of ALS is death of motor neurons, nerve cells that control muscle movements. A central question in ALS is why, and how, these neurons die. Nine new projects examine different aspects of that question.
Researchers have found that some motor neurons are more susceptible than others to the disease process. Now, they will examine how these different cells vary in the genes they express during the disease, looking for clues that influence vulnerability to ALS. Researchers will also investigate the details of the pathways by which motor neurons die, in order to improve prospects for interrupting those processes. [Aebischer, Tsunemi]
While it is motor neurons that die in ALS, evidence has accumulated to suggest that other cell types contribute to the disease. Researchers will use mice that express the disease causing SOD1 gene in multiple different cell types, to examine the role each plays. Researchers will also investigate changes at the junction between nerve and muscle to determine how muscle contributes to the disease. Finally, they will ask whether new compounds that aid the cell’s powerhouses can reduce the harmful effects of one type of cell. [Roos, Manuel, Cassina]
A newly discovered, pervasive form of gene regulation involves so-called “micro-RNAs,” which act at many different levels to control cell function. Recently researchers have leaned that micro-RNAs are altered in models of ALS, suggesting they may be a key to understanding the disease process. Researchers will extend these studies to further explore this phenomenon. [Moeller]
Researchers will further their investigations of a newly discovered cause of ALS, the protein TDP-43, to determine how the abnormal protein accumulates and why it causes disease. Understanding this may help explain how different causes can lead to the same disease, and whether there are common “downstream” targets in each form of ALS that would be appropriate therapeutic targets. [Petrucelli, Sanelli, Morton]
Why is mutant SOD1 toxic?
Mutations in the superoxide dismutase (SOD1) gene cause about 2% of all cases of ALS, but it is not yet clear how this mutation leads to the disease. Two projects examine that question, which should help in understanding not only SOD1-caused ALS, but possibly other forms as well.
Researchers know that mutant SOD1 protein forms insoluble clumps in ALS motor neurons, but it is possible that soluble forms of the mutant protein are actually more toxic. Now, researchers will study these soluble forms to understand how they affect motor neurons. [Marklund]
Researchers will also examine whether and how the cell environment affects the toxicity of SOD1, an important step in determining whether altering that environment might potentially be beneficial. [Carri]
What can we learn from new animal models of ALS?
Animal models are vital to understanding ALS and searching for treatments. A new model uses the fruit fly, whose advantages include its rapid generation and extensive understanding of its genetics. This model will be used to explore a new ALS gene to investigate how this gene causes the disease, and how other factors contribute to the disease. Another model will place a newly discovered ALS gene into mice to investigate how this gene causes the disease. [Tsuda, Dupuis]
Can imaging be used to track disease progression?
Researchers will build on previous studies to determine if magnetic resonance spectroscopy can be used to discover biomarkers of disease progression in ALS patients. This non-invasive technique is related to the more common MRI (magnetic resonance imaging), but provides additional information about chemical compounds in the body. Researchers hope that this technique will reveal one or more compounds that change in step with the disease, allowing it to be used to accurately track disease progression. [Benatar]
How can transplanted motor neurons be optimized for therapy?
One potential therapy for ALS would be to transplant healthy motor neurons into the spinal cord. However, functional motor neurons need long extensions, called axons, to reach their targets, and growing these axons in transplanted cells is an unmet challenge. Researchers will examine whether genetically modifying motor neurons can help them to better grow axons after transplantation. [Strittmatter]