MDA recently announced that it has awarded a research infrastructure grant totaling $550,000 to Jeffrey Rothstein, M.D., Ph.D., Professor of Neurology and Neuroscience and Director, Robert Packard Center for Answer ALS Research, Johns Hopkins University School of Medicine. Answer ALS is a nationwide consortium assembling one of the most comprehensive clinical, genetic, molecular, and biochemical assessments of amyotrophic lateral sclerosis (ALS) to date.

The new MDA grant will fund the development of computational tools that can integrate and analyze complex ALS disease networks.

Flexible, interpretable models of cellular pathways  

The Answer ALS and MDA partnership will develop a series of tools, known as probabilistic graphical models (PGMs), that aim to specifically interrogate and interpret combined Answer ALS datasets.

PGMs have been used extensively in applications from finance to artificial intelligence and healthcare diagnostics. These flexible, interpretable models are able to identify and quantify changes in cellular pathways.

Creation and application of PGMs to enable integrated models of this comprehensive ALS dataset can enhance understanding of disease mechanisms and advance the discovery of targets for effective therapy.

Data is key

Answer ALS research is directed by Rothstein, a longtime MDA grantee.

“This is the largest initiative aimed at understanding subgroups of ALS and finding drug targets,” says Rothstein. “The data is key. The Answer ALS initiative could pull more than six million datapoints per patient and help uncover multiple pathways of disease, pinpoint new drug targets and biomarkers, and discover novel ways to integrate the data into drug discovery.”

The overarching goal is to end ALS

Through the Answer ALS program, 1,000 ALS patients across the United States will be monitored for one year. Disease measures such as breathing function and muscle strength will be captured at clinical visits, but participants will also use an “app” that will allow them to track disease progression at home.

Biospecimens such as blood and cerebrospinal fluid will also be collected, allowing for analysis of DNA, RNA, protein, and cellular pathways, as well as for generation of stem cell lines from ALS patients used to model “disease in a dish.”

The overarching goal of the program is to better understand, and ultimately end ALS.

Sophisticated computational tools will help mine data

The comprehensive Answer ALS dataset will generate over 20 trillion datapoints, and MDA’s grant will fund the development of new data analytics approaches to support the integration and analysis of this massive amount of data, which will be shared openly with the global research community.

“Mining this rich, complex dataset with the goal of identifying ALS disease subtypes requires sophisticated computational tools,” says MDA Scientific Program Officer Amanda Haidet-Phillips, Ph.D. “The project investigators will develop a series of tools to specifically interrogate and interpret the combined Answer ALS datasets, leading to an improved understanding of ALS.”

Community support

The Answer ALS initiative has garnered wide support from not only foundations, but also from major organizations such as the National Football League, Google, IBM Research, American Airlines, Microsoft and the PGA Tour.

“We are incredibly fortunate to have partnered with Professor Ernest Fraenkel and his team at MIT, true experts in the field of data analytics, as we embark on this remarkable study,” Rothstein says.

ALS is a progressive disease of the nerve cells that leads to loss of voluntary muscle control, paralysis, difficulty speaking, swallowing and ultimately, breathing. Today, it is recognized that ALS is unlikely to be one disease; rather, it may be a collection of subtypes and variants, each of which requires a different approach for optimal treatment.

MDA is committed to finding treatments and cures for ALS

MDA has funded more than $160 million in ALS research since 1950, and is currently funding 41 active ALS grants, with a total funding commitment of $11.4 million.

The new grant was approved by MDA’s Board of Directors after careful deliberations and analysis by MDA advisors and research staff. Currently, MDA is funding 169 research projects around the world.

For more, be sure to check back at mda.org.