Embracing the concept that the whole is greater than the sum of its individual parts, an $11.5 million "disease team" grant has been awarded to UC San Diego to fast track stem-cell research on Amyotrophic Lateral Sclerosis (ALS) — also known as Lou Gehrig's Disease. The goal is to advance basic research to human clinical trials within four years.
Funding is from the California Institute for Regenerative Medicine (CIRM), the state stem-cell agency created by voter passage of proposition 71. In a public meeting on June 23, local scientists, health advocates and CIRM leadership described the grant's research focus.
ALS is a progressive, fatal disease in which motor neurons, the nerve cells that control voluntary muscle contractions, simply die. Over time, ALS leads to extreme muscle weakness, paralysis, and death.
"Like most cells in the body, motor neurons do not live in isolation; they live in an environment, surrounded by other type of non-neuron cells," said Larry Goldstein, Ph.D., professor of cellular and molecular medicine at UCSD School of Medicine, Howard Hughes Medical Institute Investigator and director of the UCSD Stem Cell Program.
"Therefore, one of the ways you might image to eliminate (disease) spread would be by supporting the 'neighborhood' rather than replacing the neurons themselves."
This has led to interest in exploiting a special type of cell called an astrocyte progenitor. Astrocytes are glial cells, a family of cells that support the proper functioning and insulation of neurons. Astrocytes, in particular, help with neurotransmissions and neuronal metabolism. Previous studies indicate that transplanting healthy glial cells into patients could be a possible treatment for ALS, and animal studies have shown that astrocytes possess particular promise in this regard.
Co-principal investigators on the grant are Goldstein, Martin Marsala, M.D., professor in the UCSD School of Medicine's department of anesthesiology, and Sam Pfaff, Ph.D., a professor in the Salk Institute's Gene Expression Laboratory. They will lead researchers in studies of two methods of administering progenitors in animal models and test the safety and efficacy of these approaches, with the goal of providing proof-of-principle and laying the groundwork for clinical trials.
"Any novel treatment option would not only be clinically competitive, but could have a major impact for thousands of patients currently battling this disease," Don Cleveland, Ph.D., professor of Medicine, Neurosciences and chair of the UCSD Department of Cellular and Molecular Medicine, stated in a press release. Cleveland is also head of the Laboratory of Cell Biology at the Ludwig Institute for Cancer Research based at UCSD. "This approach has the potential to lead to the development of new therapies that could significantly extend the lifespan of individuals living with this disease, and improve their quality of life."
In addition to basic research, animal data, and pre-clinical aspects of the studies, another disease-team member is Carlsbad-based Life Technologies Corp. which will provide expertise in stem-cell biology, cell separation, next-generation sequencing, and scalable bioproduction.
"The goal is to develop a clinically compliant process for preparation of human astrocyte precursors," said Mark Bonyhadi, Ph.D., director of clinical business development for cell therapy systems at Life Technologies.
Approximately 30,000 people in the United States are affected with ALS with 5,600 new cases diagnosed each year. The causes of ALS are unknown; there is no cure. Only one drug — Rilutek — is currently approved by the Food and Drug Administration for treating ALS. Rilutek extends the lifespan of ALS patients by a maximum of three months.