"The film So Much So Fast captures year 2.5 through year four of an eight-year-old organization," explained Jamie Heywood as he showed a visitor around the lab of the ALS Therapy Development Institute (ALS TDI), the organization he co-founded in 1999, after his brother Stephen was diagnosed with ALS.

Since 2004, when the filming ended, the foundation has grown significantly:

• It has built a world-class research lab in Cambridge, Mass., with nearly 35 employees and a $12 million operating budget
• It's tested more than 700 drugs and completed more than 250 studies in genetically engineered mice -- more than all other ALS labs combined.
• It's spun off a for-profit biotech company, ALSGEN, to develop treatments for familial ALS. ALSGEN has a drug about to be tested in animal models.
• It has two drugs in clinical trials and a third on the way.

From the beginning, the foundation -- whose early years were chronicled in a February 2000 New Yorker article and a book, His Brother's Keeper: A Story From the Edge of Medicine, by Jonathan Weiner -- brashly set out to break the protocols of the drug discovery process and change the paradigm for "disease nonprofits." Rather than fundraising, the organization, then known as the ALS Therapy Development Foundation (ALS TDF), declared that it "exist[ed] purely to develop treatments for the patients living with ALS today, not to raise money for research papers." It announced it was stepping into the gap in the health care system between the profit motive of pharmaceutical companies, which were unlikely to recoup costly research & development investments for orphan diseases such as ALS, and risk-averse academic institutions, where researchers moved slowly, spending years to prove a theory that might lead to a drug.

The foundation's initial mission was very personal: finding a cure for Stephen Heywood. Though Stephen participated in some of Jamie's research -- he became the first recipient of a radical gene therapy attempt, and for three years, he took an experimental drug for sickle-cell anemia -- neither therapy worked.

Stephen's November 2006 death has not changed the foundation's goals. It is continuing to test possible new drugs and is challenging both its own research and others'. Foundation scientists have an upcoming paper accepted for publication that outlines their unsuccessful attempts to replicate the successes in animal studies that have led to clinical trials. The ALS TDI research team concludes that: "unless the studies were tightly controlled, noise in the experimental system would swamp most signals and could be interpreted as a positive result."

In January 2007, ALS TDI announced a $36 million partnership with the Muscular Dystrophy Association to form the world's largest research program dedicated to the discovery of drugs to treat ALS. The MDA and ALS TDI each will grant $6 million per year over three years to the project; research will take place at the ALS TDI's Cambridge facility and ALS TDI will have access to patients through the MDA's nationwide network of clinics.

The money will fund an ambitious seven-year plan, launched in 2006, to target six "critical gaps" in ALS research, including:

• Discovery Research: Looking more closely at the genes involved or altered in ALS
• Biomarker Development: Learning which genes or proteins act as "diagnostic markers" or evidence of disease progression
• Target Validation: Figuring out which altered genes are the most promising targets for drugs or gene therapy
• Drug Screening: Determining which existing drugs have an impact on the disease
• Open Science: Sharing all data in real time
• Clinical Trials: Discovering what works in humans

However, according to Jamie, the influx of funds will not change the foundation's philosophy. "ALS TDI has always been and will always be focused on discovering effective treatments for today's patients using an entrepreneurial spirit and combining the power of a nonprofit mission with the best practices of a for-profit biotechnology company."

 

More about ALS TDI can be found on its Web site.

Update: In August 2007, Jamie announced his resignation as CEO. "It has been an honor to lead ALS TDI, and I am very proud of the institute and team that have built it. I know that the research program is in good hands and this is the right moment to move on to new challenges," he said in a statement. He will remain on the institute's Board of Directors, and Sean Scott, who began as a volunteer after his mother was diagnosed with ALS and rose to become president of ALS TDI, will lead the organization.