Biogen, a global biotechnology company, the ALS Association, a national non-profit organisation fighting Lou Gehrig’s disease, and Columbia University Medical Center (CUMC) have entered into a new collaboration to better understand the differences and commonalities in the amyotrophic lateral sclerosis (ALS) disease (Lou Gehrig’s disease) process and how genes influence the clinical features of the disease.

The project, “Genomic Translation for ALS Clinical care” (GTAC), will involve a combination of next generation genetic sequencing and detailed clinical phenotyping in 1500 people with ALS. The goal of the project is to provide a basis for the development of precision medicine or more individually tailored therapies for ALS.

“We want to bring genomics right to the point of care in ALS where instead of focusing on retrospective DNA samples with limited clinical information, we focus on patients who are under active clinical management,” said ALS Association chief scientist Lucie Bruijn, Ph.D., M.B.A.

“By focusing on patients seen by participating ALS clinics, this project will allow investigators to ask how different genetic causes of ALS translate into different clinical consequences.”

An explicit aim of the collaboration is to set the stage for a nationwide effort to ensure the genomic characterisation of all patients with ALS.

“We know that ALS is not just one disease. This study will help in developing a detailed understanding of how different genes contribute to different clinical forms of ALS. This will in turn help us design better, more focused clinical trials for the development of more effective treatments. This kind of ‘precision medicine’, in which a treatment is tailored to a person’s unique genetic make-up, is already being used in the cancer field. It is an approach we feel is ready for ALS too,” explained Tim Harris, senior vice president, precision m at Biogen.

“Until recently, most large-scale genomics studies used archived DNA samples, so the findings had minimal impact on patient care,” said David B. Goldstein, Ph.D., professor of genetics and development and director of the Institute for Genomic Medicine at CUMC.

"This project reflects our commitment to using ALS genomic studies to benefit patients directly through diagnoses and to set the stage for genetically stratified clinical trials.”

“This project will provide a clinical deliverable to the 1500 patients that participate in the study. We will use our extensive database of ALS genomes and exomes to carefully identify definitive genetic risk factors for ALS and these risk factors will be communicated back to participating clinics. The database we create will allow for an unprecedented investigation of the clinical correlates of the genetic causes of ALS.” said Dr. Matthew Harms, M.D., who will lead the project and be joining CUMC in the fall as an assistant professor of neurology.

Patient blood cells will be stored at the induced pluripotent stem cell (iPSC) core, a facility supported by the ALS Association, at the Cedars-Sinai Board of Governors Regenerative Medicine Institute. This cell bank will allow researchers to create cell lines for further study, based on leads provided by genome sequencing.

“The ability to create patient iPS cells from such a genetically well-annotated ALS blood repository will allow us to model causes of motor neuron degeneration in ALS at a scale that has never been possible,” said Dhruv Sareen, Ph.D., who leads the Cedars-Sinai iPSC Core.

Clinical data will be collected and curated through the NeuroBank system at the Massachusetts General Hospital, and cell lines will be developed at Cedars-Sinai in Los Angeles. Currently, participating clinical sites in this effort include the Cedars-Sinai Board of Governors Regenerative Medicine Institute, Columbia University Medical Center, Duke Medical Center, Houston Methodist, the Scotland ALS clinic network, University of Minnesota and Hennepin County Medical Center, University of Utah, University of Washington, and Washington University in St. Louis.

The project is being funded through Biogen’s $30 million strategic alliance with CUMC and $3.5 million from the ALS Association. The ALS Association’s commitment comes from funds raised directly through the Ice Bucket Challenge.

ALS is a progressive neurodegenerative disease that affects neurons (nerve cells) in the brain and the spinal cord. Eventually, people with ALS lose the ability to initiate and control muscle movement, which often leads to total paralysis and death within two to five years of diagnosis. There is no cure and no life-prolonging treatments for the disease.