ALS experts talked about the state of research, and industry leaders discussed ways to improve the pace and efficiency of ALS drug development at the 2011 ALS TDI Leadership Summit, Nov. 4, 2011. The Summit, an annual conference hosted by the MDA-supported ALS Therapy Development Institute (ALS TDI), took place in Cambridge, Mass., and was broadcast live over the Internet.
The Summit webcast has been archived on ALS TDI's website and is available for viewing to all who log in or register.
In recapping Summit presentations about current ALS research, ALS TDI CEO and Chief Scientific Officer Steve Perrinnoted the conspicuous absence of discussion focused specifically on motor neurons (nerve cells), which die in ALS.
Instead, Perrin said, researchers are focusing on the involvement of other cell types in ALS and the need to modulate them “to become good players, not bad players.”
A number of compounds targeted to act on numerous elements of the ALS disease process are in various stages of development in the ALS TDI pipeline — from discovery of new leads, to formulation of experimental therapeutic agents, to preclinical testing in cell culture and in animal models.
Neurologist Merit Cudkowicz, director of the MDA/ALS Center at Massachusetts General Hospital in Boston and a longtime MDA research grantee, talked about a “therapeutic revolution for treatment in ALS” due to a large pipeline that includes drugs, gene therapy and stem cells.
Cudkowicz noted that the identification in 1993 of the SOD1 gene responsible for some cases of familial (inherited) ALS, along with the subsequent discovery of an additional 16 ALS-associated genes, has increased the speed of research. This, she said, is because every new gene "gives us tools to develop treatments." Each discovery brings in new researchers, new ideas, new pathways and targets, and new enthusiasm.
Stanley Appel, chairman of MDA's Medical Advisory Committee (MAC) and director of the MDA/ALS Center at Methodist Neurological Institute in Houston, presented information about his study of immune-system-based T cells. Appel has an MDA grant to study the protective effects of these cells.
John Lincecum, ALS TDI director of research biology, discussed the nonprofit route to protein-based therapeutics (protein biologics). ALS TDI, he noted, is looking for the fastest route to treatments, and while development of protein-based strategies can sometimes be more difficult, it also provides opportunity for speed.
Protein-based treatments potentially may compensate for nonfunctional, dysfunctional or missing proteins, or may interfere with proteins that are toxic to neural cells or cellular subcomponents such as mitochondria. These strategies are powerful, but come with a greater risk of unwanted effects than some other types of drugs, such as small molecules.
Jeffery Rothstein, a professor of neurology at Johns Hopkins University in Baltimore and director of the MDA/ALS center at that institution, presented data from his studies of NG2 cells, a population of stem cells that mature into a particular type of central nervous system support cell called oligodendrocytes. (For more on NG2 cells, see ‘New and Important Player’ Advances Understanding of ALS, ALS News, Dec. 3, 2010.)
ALS TDI Director of Research Operations Fernando Vieira presented an update on ALS TDI's study of the recently developed TDP43 research mouse model.
Vieira noted that a collaboration announced March 22, 2011, between ALS TDI, the Muscular Dystrophy Association, the Alzheimer's Drug Discovery Foundation and the Association for Frontotemporal Degeneration has fueled the Institute's study of the mouse and that ALS TDI is now nine months into an 18-month plan to characterize (describe the qualities and features of) the TDP43 model.
Study data will help determine whether the mouse is a good fit for drug testing in ALS and, if so, will ensure optimal quality and efficiency in preclinical testing.
The goal, Vieira said, is to make sure that, if the model is going to be used in ALS research, it's used in the most effective way possible. If it turns out that the TDP43 mouse isn't useful in ALS research, Vieira noted, they want to find this out as quickly as possible.
For more on the TDP43 mouse model, which carries a mutation in the gene for the TDP43 protein and was engineered by MDA-supported scientists, see New ALS Mouse, ALS News, Oct. 8, 2009.
In a panel discussion, leaders representing biotechnology and pharmaceutical companies, venture capitalist organizations and government agencies offered their thoughts on speeding therapy development.
Participants included Douglas Onsi, managing director at the life science venture capital firm Healthcare Ventures; Henri Termeer, former chairman of the board and chief executive officer at the biotech company Genzyme; George Scangos, chief executive officer of biotech firm Biogen Idec; Robert Blum, chief executive officer of the pharmaceutical company Cytokinetics; and Christopher Austin, scientific director at the National Institutes of Health Center for Translational Therapeutics.
Common themes throughout the discussion included:
All expressed optimism about the present-day search for ALS therapies. Onsi referred to it as “an era of transformation in ALS research” and “an incredibly hopeful time.”
The efforts under way to bring therapies to people with ALS are gaining traction.
“Today,” Termeer noted, “the sense is that we can get there.”
ALS TDI regularly hosts webinars on a variety of ALS-related topics. To view archived versions of previous Web events or to see what’s coming up, see the webinar schedule.
View the archived recording of ALS TDI’s 2011 Annual Leadership Summit at the Institute’s website. (Note: Registration is required to view the webcast.)
Through its Augie’s Quest ALS research funding initiative, the Muscular Dystrophy Association provides funding to support ALS TDI’s ALS drug development program. Since 2007, MDA has awarded grants to the Institute totaling more than $23.4 million.