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ALS Alert Newsletter

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May 1

Answer ALS researchers meet in Baltimore

Annual symposium shows project is on schedule and already looking toward the future.

In 2013, ALS patient activist Steve Gleason had the idea to bring together ALS researchers and patients to end the disease. What resulted was Answer ALS. With philanthropic support, researchers from eight ALS clinical centers around the US will enroll 1000 ALS participants and follow them for at least one year. The scientists involved in Answer ALS will use genomics, transcriptomics, epigenomics, proteomics, metabolomics (collectively referred to as “omics”), combined with serial neuronal imaging to create the largest biological database on ALS. Each patient will yield more than six billion data points with the goal of identifying the individual biochemical and molecular pathways that we know as ALS.

Alexander Sherman and Jeff Rothstein confer between presentations at the annual Answer ALS symposium.

At this year’s meeting, two new groups from Texas Neurology in Dallas and Northwestern University in Chicago joined the Answer ALS team. Even without these new teams, enrollment in Answer ALS remains on course, which is rare for a large, long-term study. In the 30 days before the symposium, 26 participants were recruited. Thus far, 720 study participants have completed their first visit, and 405 completed their second visit. As enrollment in Answer ALS approaches the December 31, 2018 finish line, researchers are drafting a plan to give participants the option of receiving their genetic testing results. They have also begun work on facilitating autopsies to get samples from participants who have died.

The stem cell group has begun work on creating the world’s largest set of ALS induced pluripotent stem cells (iPSCs) and differentiated motor neurons. To date, they have 300 cell lines complete, 220 of which are available with clinical data. The researchers created a spreadsheet to allow researchers to sort by mutation type, demographics, and other data before selecting the lines most suitable for their research. The team has been developing newer, shorter differentiation protocols and comparing the quality of data to older, more expensive methods. The transcriptome of differentiated cells can be analyzed by RNAseq, which sequences all the messenger RNA molecules in an individual cell.

Answer ALS director Emily Baxi at the annual Answer ALS meeting recently held in Baltimore.

Before scientists move forward to generate and analyze the other types of omics data, they have been performing extensive quality control checks with the samples to make sure everything is accurate, and all methods have been fully optimized. Answer ALS scientists are working to develop a data transfer pipeline for the project. This pipeline will facilitate data sharing not only amongst the team members, but ultimately with the global ALS research community. Along with other types of data analysis, Dr. Ernest Fraenkel, a Professor of Biological Engineering at MIT, is building algorithms to zoom in on the relevant portions of molecular networks. Although preliminary, researchers are already seeing the power of combining clinical and omics results to produce more robust results.

Leslie Thompson of the University of California, Irvine presents at the 2018 Answer ALS annual meeting.

The New York Genome Center is performing the DNA sequencing on participant samples. One of the major challenges for the projects isn’t the sequencing but annotating the genomes, which is what really yields information about what genes do, where mutations are located, and if/how they might contribute to disease. To date, the team has identified 28 million variants (130 of which are likely pathogenic) in 230 samples. Researchers have also identified several genes that are expressed differently in ALS participants compared to controls, results that could provide important insights into what goes wrong in ALS.

A novel aspect of Answer ALS is the iPhone app being developed and analyzed by teams at Johns Hopkins University and IBM Watson. The app will gather daily information using different voice, speech, and various motor tasks that will allow researchers to collect information about disease progression between clinic visits. The IBM team used new software tools to analyze voice and speech patterns submitted through the app to extract more detailed information about disease course.

The new Answer ALS iPhone app was introduced at the annual meeting.

With less than a year to finish enrolling participants, one part of Answer ALS may be drawing to a close, but it’s clear that scientists have just begun their work.