This fall, Project ALS added four eminent scientists to its outstanding Research Advisory Board. Their resumes are impeccable and their achievements make us nervous to share a room with them (see below), but you may wonder: when people are fighting for their lives every day against ALS, why is this big news?
The answer is what sets Project ALS apart from any other organization working to stop this devastating disease: we bring the brightest scientists from every discipline to wage battle with ALS. Instead of issuing cumbersome requests for proposals or waiting for scientists to contact us for funding, we put our Research Advisory Board (RAB) to work finding the most promising pilot studies, talented researchers, and bold ideas that may pay off big in understanding and treating this complicated brain disease. By identifying the most promising novel approaches to ALS research, shaping incisive, collaborative projects to probe them, and actively managing research results, Project ALS RAB sets the agenda for the entire ALS research field.
Case Study: ALS in a Dish
Project ALS was the first to ask if stem cells might help us understand, slow, or even stop ALS. In 2000, we asked our RAB to find us the top stem cell experts, most of whom had never studied ALS before. In short order, they recruited experts from Children’s Hospital Boston, Johns Hopkins University, Columbia University, Memorial Sloan Kettering Cancer Center, and Harvard University, to explore how stem cells might help people with ALS. In 2006, the Project ALS RAB recommended that we open the Jenifer Estess Laboratory for Stem Cell Research, the first and only privately funded laboratory to focus exclusively on stem cells in ALS, to more effectively build on initial promising results.
A collaboration led by the Project ALS team of experts developed, in 2008, the “induced pluripotent stem cell” (iPS) model, allowing researchers to create an ALS patient’s motor neurons in a dish from a simple skin punch. This extraordinary breakthrough, sometimes called “ALS in a Dish” for its ability to effectively model human brain disease outside of the body for the first time, can be used to screen for drugs more efficiently and understand what happens to motor neurons in ALS in an actual person living with the disease.
Now, iPS cells are used in brain disease research around the world. In the ALS field, every organization utilizes these important model tools. Target ALS, the NEALS Consortium, and the Packard Center are creating iPS “banks” to use for proof-of-principle trials for better ALS drug candidates. The ALS Association is co-funding a Phase II clinical trial with pharmaceutical company GlaxoSmithKline based on the Eggan lab discovery that retigabine, an FDA approved drug for epilepsy, improved motor neuron survival in the iPS model. ALS TDI has taken skin samples from 200 patients to create their own personal iPS lines and model their “ALS in a Dish.” Numerous academic labs, biotechs, and pharmaceutical companies are probing the brain using this Project ALS-developed technology.
The ALS research field has exploded in the past five years. Over twenty-five genetic causes of the disease have now been identified. Pharmaceutical companies, recognizing that breakthroughs in ALS can also inform drug development for related neurodegenerative diseases like Alzheimer’s and Parkinson’s, have begun to take a financial interest in ALS research. The Ice Bucket Challenge brought a windfall of research dollars and public awareness to ALS last year.
Now is the time to take bold, creative approaches toward stopping ALS. In adding Juan Burrone, Fred Goldberg, Bob Horvitz, and Jeff Porter to the Project ALS RAB, we bring invaluable new perspectives, and brilliant new ideas, to guide the ALS research field:
Juan Burrone is an expert in brain circuitry at King’s College London, whose work characterizing “synaptic transmission”—how neurons communicate with each other—will offer important new insights into how motor neuron support cells, like interneurons, astrocytes, and microglia, impact motor neuron survival in ALS.
Fred Goldberg, from Harvard Medical School, first discovered and characterized the “ubiquitin-proteasome pathway,” which is responsible for protein metabolism in the cell. A breakdown in protein metabolism, leading to the accumulation of plaques or tangles, is a hallmark of ALS and other neurodegenerative diseases, and Dr. Goldberg has already identified therapeutic targets that may fix proteasome function in ALS.
H. Robert Horvitz is a researcher at the Massachusetts Institute of Technology, where his work on “apoptosis”—programmed cell death—earned him the Nobel Prize in 2002. Dr. Horvitz, in collaboration with Project ALS RAB colleague Bob Brown, identified the first familial genetic mutation (SOD1) in ALS. Dr. Horvitz’s interest in Project ALS is deeply personal: his father died from ALS in 1990.
Jeff Porter, Head of Developmental and Molecular Pathways for Novartis Institutes for BioMedical Research, offers invaluable insight into ALS drug development. His team at NIBR is responsible for identifying pathways that go wrong in disease, and finding the right drug to treat them—making his counsel of vital importance as we identify new therapeutic targets in ALS.