Biogen is expanding its research alliance with Columbia University Medical Center (CUMC) to better understand commonalities and differences in the amyotrophic lateral sclerosis (ALS) disease process by building a database of genes and traits from 1,500 people with the debilitating neurodegenerative disorder, also known as Lou Gehrig’s disease.
Using next-generation genetic sequencing and detailed clinical phenotyping, researchers—working with the ALS Association—will study how genes influence the clinical features of ALS as part of a precision medicine goal to provide a foundation for the development of more individually tailored ALS therapies. Unlike previous genetic studies, the currently treated ALS patients will be studied to find mutations that appear to hasten or slow the disease progression.
“This study will help in developing a detailed understanding of how different genes contribute to different clinical forms of ALS,” said Tim Harris, Biogen’s senior vice president of precision medicine. “This will, in turn, help us design better, more focused clinical trials for the development of more effective treatments.”
Most ALS studies have been based on patients who have died, where researchers are looking for the absence or presence of certain genes linked with ALS. A progressive disorder that affects nerve cells in the brain and spinal cord, 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.
“ALS does not present the same way in every person, and that is why it’s a hard challenge to develop appropriate treatments and group patients based on genetics, which is what we’ve seen in precision medicine for people with cancer,” said Lucie Bruijn, Ph.D., chief scientist at the ALS Association. “We hope to find some interesting and new genetic changes in subgroups of patients that are validated. We think we’ll get better analyses from those living with the disease where we are looking at certain points, compared to past studies where there might be missing or incomplete data and not have the same depth and analysis, which lacked consistent scientific rigor. We believe this project will allow investigators to ask how different genetic causes of ALS translate into different clinical consequences.”
The three-year project, called “Genomic Translation for ALS Clinical Care,” is being partially financed out of the $115 million that the ALS Association raised from the viral fundraising program known as the Ice Bucket Challenge, which featured people dumping buckets of ice water over their heads and challenging others to do the same. The ALS Association is giving $3.5 million to the project, with Biogen funding the balance as part of the biotechnology company’s $30 million collaboration in genetics research with Columbia University.
The Biogen partnership also comes nearly 2½ years after a 943-patient phase III trial of dexpramipexole, a proposed ALS therapy, was halted and called a “spectacular failure” by company CEO George Scangos.
An explicit aim of the new collaboration is to set the stage for a nationwide effort to ensure the genomic characterization of all patients with ALS—estimated at 20,000 Americans at any given time, with about 6,400 people newly diagnosed with the disease each year, according to the ALS Association.
The study is expected to help develop a detailed understanding of how different genes contribute to different clinical forms of the disease. For each of the 1,500 ALS patients, the project will provide a clinical deliverable and use an extensive CUMC database of ALS genomes and exomes (parts of the genome formed by exons, which are the coding portions of genes that are translated or expressed as proteins) to identify definitive genetic risk factors for ALS.
“The database we create will allow for an unprecedented investigation of the clinical correlates of the genetic causes of ALS,” Matthew Harris, M.D., said in a prepared statement. He will lead the project and join CUMC in the fall as an assistant professor of neurology.
The three organizations’ quest to map the disease genes also will rely on two major bicoastal research medical centers to create tools that will eliminate some of the mystery from ALS, in terms of its causes and care. Clinical data will be collected and curated through the NeuroBank system at Massachusetts General Hospital, with patient blood stored at the Induced Pluripotent Stem Cell Core (iPSC Core), a facility at the Cedars-Sinai Board of Governors Regenerative Medicine Institute in Los Angeles. From that cell bank, researchers will be able to create cell lines from each of the 1,500 ALS patients into specific cells of the human body including components of the nervous system, eyes, blood, bones, heart, gut, liver and pancreas for researchers to examine.
“The ability to create patient-induced pluripotent stem 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,” Dhruv Sareen, Ph.D., who leads the Cedar-Sinai iPSC Core, said in a prepared statement.
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