Science - Teaming up for ALS

Our consortium approach to discovery

July 14, 2017

I’m a fanatic about three things: fruit flies (see my other post, Fly Aficionado), drug discovery, and basketball. I’ve played serious basketball, pick-up games, and H-O-R-S-E with my kids. The game is about cooperation, teamwork, chemistry, trust, strategy and passion - all elements I’ve found necessary in scientific discovery and discovering new therapies. So, when Biogen launched our ALS Consortium in 2012, it was an opportunity to segue my skills from the court into overseeing a large, coordinated academic-industry research effort into this complex neurological disease.

Playing for keeps
Amyotrophic lateral sclerosis (ALS), also called Lou Gehrig’s disease, affects nerve cells that control voluntary muscle movement and has no cure. In 90% of patients, it occurs spontaneously, and the molecular underpinnings remain a mystery. The goal of the ALS Consortium was to accelerate our understanding of ALS disease mechanisms, and to investigate novel targets and treatment approaches. Its strength relied on trust, and the willingness to share information and emerging insights across different disciplines.

A well-rounded all-star team
One unique feature of the consortium was to bring in scientists who are highly regarded experts in their field, but not necessarily focused per se on ALS. They were brought together to bring new perspective to the disease. Like a basketball team, each member of the consortium played a critical role and helped move the ball closer to our ultimate goal. The seven groups in the consortium met their objectives, and I’d like to highlight a few examples of new knowledge gained.

Marc Tessier-Lavigne’s group at Rockefeller University was interested in determining whether removing a specific gene in a SOD1 ALS disease model (SOD1 was the first gene genetically linked to ALS) would confer protection against the disease. To their surprise, they found that loss of the gene of interest delayed onset but actually seemed to accelerate disease progression.

Art Horwich and his group at Yale University/Howard Hughes Medical Institute (HHMI) elegantly showed that in a disease model, mutant SOD1 protein could spread to healthy motor neurons and “infect” them. Thus, if we can identify ways to block or inhibit this transmission mechanism, we may be able to slow disease progression.

Groups working on basic cellular processes, Pietro de Camilli at Yale University/HHMI and J. Wade Harper of Harvard Medical School, shed insights into how cellular dysfunction can contribute to ALS, and possibly other neurodegenerative diseases.

The next play
Where do we go from here? Generally speaking, good science will lead to answers, however, those answers will always lead to additional questions. We, as a community, need to work through these iterative questions, and strategize our playbook.

The ALS Consortium is a prime example of how collaborative work among a diverse, and at first, unrelated range of scientists, can develop new insights into how we can target this complex disease.

Mark Kankel, Principal Scientist, Neurology

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