Biogen, the ALS Association and Columbia University Medical Center (CUMC) have formed a collaboration to better understand the differences and commonalities in the amyotrophic lateral sclerosis (ALS) 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 1,500 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 characterization of all patients with ALS.
“We know that ALS is not just one disease,” said Tim Harris, senior vice president of precision medicine at Biogen. “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 makeup, already is being used in the cancer field. It is an approach we feel is ready for ALS too.”
“This project will provide a clinical deliverable to the 1,500 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 Matthew Harms, M.D., who will lead the project and join 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. The cell bank will allow researchers to create cell lines for further study, based on leads provided by genome sequencing.
Clinical data will be collected and curated through the NeuroBank system at 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; CUMC; 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.