ALS: New MDA Grants Focus on Multisystem Aspects of the Disease

Three new MDA grants totaling $891,156 have been awarded to research projects aimed at uncovering some of the many complex processes that underlie ALS.

"Scientists are digging ever deeper into the underlying mechanisms at work in ALS,” said Sanjay Bidichandani, MDA’s vice president of research. "MDA is pleased to support research efforts aimed at getting to the bottom of this devastating disease, in the hopes that they’ll spark ideas for the development of new treatments."

The grants took effect Aug. 1, 2012.

One disease, numerous contributing causes

Green fluorescent protein illuminates the muscle-controlling nerve cells called motor neurons in a C. elegans (nematode, or roundworm) research model of ALS. NOTE: Click on photo to expand.

In recent years ALS has been redefined. What once was thought to be a disease affecting only the muscle-controlling nerve cells called motor neurons now is known to be a multisystem disorder with processes going awry in multiple cell types and numerous biological pathways.

Scientists are looking at:

  • parts of cells, such as the cellular compartment involved in protein transport called the endoplasmic reticulum;
  • cellular responses to the stress caused by a toxic environment; and
  • modifiers that can affect disease risk, onset and progression.

Each of the three new research projects receiving MDA support tackles a specific factor — or factors — that may contribute to the overall course of ALS.

Cell survival

Two of the new grants focus on cell survival mechanisms.

A better understanding of one of these mechanisms, the endoplasmic reticulum (ER) stress response is the subject of MDA's $231,300 grant to Alex Parker, assistant professor in the department of pathology and cellular biology at the University of Montreal Hospital Research Center in Montreal, Quebec (Canada). 

The ER stress response is known to reduce toxicity caused by mutant TDP43 and FUS proteins (each of which has been implicated in the ALS disease process). With colleagues, Parker aims to identify small molecule drugs that can boost the ER stress response to help motor neurons overcome protein toxicity and stave off cell death.

In this image, generated with an imaging technique called confocal microscopy, a cell shows stress granules after exposure to a chemical called sodium arsenite. TDP43 is shown in green, with stress granule markers G3BP in red and TIA-1 in blue. Where all three overlap, the color is purple. NOTE: Click on photo to expand.

Christine Vande Velde, a research assistant professor in the department of medicine, also at the University of Montreal Hospital Research Center, is studying another cell survival mechanism: the formation of proteins and RNA molecules into clumps called stress granules. As with the ER stress response, stress granules are associated with the TDP43 protein.

Vande Velde's $358,242 MDA grant will help support her work, conducted in cellular and rodent models, to determine the role of TDP43 in the stress granule mechanism and determine the impact of ALS-causing mutations on the pathway.

Nongenetic risk factors

Scientists have long sought to understand whether nongenetic factors — such as race, ethnicity, socioeconomic status or occupation — affect a person's risk of developing ALS.

Weisskopf and colleagues are studying the relationship between race/ethnicity, education and specific occupations, and the risk of developing ALS.

Despite a great deal of work to find out, the only factors that consistently predict risk for the disease are age (older adults are more at risk) and gender (men are slightly more likely than women to develop the disease).

With support from a $301,614 MDA grant, Marc Weisskopf, associate professor of environmental and occupational epidemiology at Harvard School of Public Health in Boston, has launched a large-scale study to search for nongenetic risk factors for ALS.

Weisskopf is using survey data from two sources: the U.S. Census Bureau and the National Death Index, which provides data on the causes of nearly all deaths in the United States since 1979.

To learn more

For up-to-date information on all the latest MDA-funded research projects, see Grants at a Glance, a slideshow feature with photos and information on the new MDA grantees and their research, and MDA Commits $10.7 Million to Neuromuscular Disease Research.

To review the approximately 300 active research grants currently being funded by MDA, view this PDF.

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