ALS Therapy Development Institute

The ALS Therapy Development Institute (ALS TDI) is a non-profit biotechnology company seeking effective treatments for amyotrophic lateral sclerosis (ALS) by using the SOD1 mouse model of ALS. It operates the world's largest research and development program focused on ALS.

History

ALS TDI was founded as the ALS Therapy Development Foundation (ALS TDF) in 1999 by James Heywood, Robert Bonazoli, and Melinda Marsh Heywood after James' brother, Stephen Heywood, was diagnosed with the disease. The foundation was initially funded through a donation from Stephen, as well as one from Alex and Brit d'Arbeloff. The Foundation's first therapy concept was to replace EAAT2 protein using gene therapy.^[2]

In 2001, the Foundation opened its first lab at the New England Medical Center and tested 27 drugs in the SOD1 mouse with two successes. The organization also received approval to conduct the world’s first stem cell trial for ALS.^[2]

The Foundation moved to a 16,000-square-foot (1,500 m²) location in Cambridge, Massachusetts in 2004, with an in-house lab.

In 2005, the Foundation became the beneficiary of the Tri-State Trek, a 270-mile bike ride from Boston to New York, founded by Mathew Mendel in 2003.

In 2006, fitness pioneer and ALS patient Augie Nieto became chairman of the board.

James served as founding director and CEO of the Foundation through 2007, when he joined the board. Following Heywood's move to the Board, Sean F. Scott, who ALS runs in his family, was named CEO.^[2] Augie Nieto worked with Scott, as well as with Sharon Hesterlee, the Vice President of Translational Research at MDA, to bring together the two organizations in 2007. As a result, TDI would received $36 million from MDA through Nieto's initiative, Augie's Quest.^[3] In addition, the organization changed its name to ALS TDI from ALS TDF.^[2]

The Institute received a $1.1 million grant from the U.S. Department of Defense in 2008 and an additional $1.6 million grant in 2010.^[2][4]

Steven Perrin, PhD, previously only Chief Scientific Officer, was appointed CEO in 2009 following the death of Scott. In addition, Stanley Appel, M.D., a board member, tells a congressional hearing that "ALS is not an incurable disease, it is an underfunded one".

MDA and Augie's Quest contributed another $2.5 million to the Institute in 2010. The Young Faces of ALS (YFALS) program was also created.

In 2011, the Institute moved to a new 26,000-square-foot (2,400 m²) facility, also in Cambridge, allowing for the hiring of more scientists and a bigger lab.^[2]

The organization launched the Precision Medicine Program in 2013 "to identify subgroups of ALS, potential treatments for them using patient data, genomics and iPS cell technology".^[5]

In 2014, Augie's Quest officially transitioned from MDA to ALS TDI.^[6]

In 2016, the Institute announced the ALS One partnership with Massachusetts General Hospital/Harvard Medical School and the University of Massachusetts Medical School to find a treatment for ALS within four years.^[7]

Research Activities

The Institute has raised and spent nearly $60 million on research into effective treatments for ALS and published several works that have helped to further the field of neuro-degenerative research, including:

• Design, Power and Interpretation of Studies in the Standard Murine Model of ALS (Scott, et al., ALS Volume 9(1):4-15, 2008)^[8]
• From Transcriptome Analysis to Therapeutic Anti-CD40L Treatment in the SOD1 Model of Amytrophic Lateral Sclerosis (Lincecum, et al., Nature Genetics, Volume 42, May 2010)^[9]

ALS TDI practices open-source science and maintains a patient and research-focused discussion forum. Some of the Institute's funding comes from grassroots fundraising events organized by ALS patients, their families and supporters.

The Institute has performed independent validation of previously published pre-clinical efficacy studies in the mutant SOD1 G93A mouse model. Using large cohorts and rigorous trial design, ALS TDI demonstrated that several promising pre-clinical compounds such as minocycline and creatine, which showed dramatic effects in high-profile publications, could not be independently reproduced.

However, many ALS researchers have raised questions about the utility and predictive power of the SOD1 G93A familial ALS mouse model for understanding and finding drugs to treat sporadic ALS in humans. A critical issue is whether the pathogenesis of the SOD1 G93A mutation (one of 120 in the SOD1 gene) is idosyncratic and further, whether pathogenesis caused by familial ALS SOD1 mutations (<4% of cases) is similar to sporadic ALS (>90% of cases). Critically, no pre-clinical compound, even those validated by ALS TDI, have actually proved beneficial even in early stage clinical trials.

References

External links

• ALS Therapy Development Institute website
• ALS.net
• Augie's Quest website
• Documentary: So Much So Fast
• His Brother's Keeper by Jonathan Weiner