A team led by Peter Schultz, Scripps Family Chair Professor and member of the Skaggs Institute for Chemical Biology at The Scripps Research Institute, has been awarded a $4.3 million grant from the California Institute for Regenerative Medicine (CIRM) to research stem-cell-based therapies to treat multiple sclerosis.
Because stem cells can change or differentiate into many different cell types (such as nerve cells, muscle cells, and skin cells), they hold the life-changing medical potential to provide a source of cells to replace those permanently lost by a patient.
The Scripps Research project focuses on restoring the myelin sheath—a protective covering that surrounds nerve cells, damaged during the progression of multiple sclerosis. Specifically, the team will try to identify potential drug candidates that act on a group of stem cells already in the central nervous system called “oligodendrocyte precursor cells” (OPCs).
“We are pursuing a new approach towards the treatment of multiple sclerosis in collaboration with Scripps Research Assistant Professor Brian Lawson,” said Schultz. “We have identified a molecule that induces oligodentrocyte differentiation and remyleniation in vitro and in vivo in animal models of MS. Moreover, the drug works very effectively in combination with existing immunotherapies. As such, we feel these could be exciting and new approaches to the treatment of this autoimmune disease.”
In 2010, Schultz approached Argyrios Theofilopoulos, chair of the Department of Immunology and Microbial Science, for a potential collaboration to assess the efficacy of novel compounds shown by his group in high-throughput systems to promote maturation of precursors to myelin-producing mature oilgodendrocytes. Lawson initiated studies in models of multiple sclerosis, in close collaboration with Scripps Research Assistant Professor Luke Lairson and graduate student Vishal Deshmukh.
“We were gratified to see the initial insights of Dr. Schultz lead to the identification of compounds that were highly effective in suppressing disease in several in vivo models, particularly when combined with current therapies such as IFN-beta and FTY720,” said Lawson. “We have great hopes that these initial findings will lead to a new approach in the treatment of MS and related neuroinflammatory demyelinating disorders. The funding provided through CIRM will greatly expedite our efforts in this exciting area.”
The new grant is part of the CIRM Early Translational Award program, which supports projects in the initial stages of identifying drugs or cell types that could become disease therapies.
CIRM was established in November 2004 with the passage of Proposition 71, the California Stem Cell Research and Cures Act. The statewide ballot measure provides $3 billion in funding for stem cell research at California universities and research institutions.
Targeting Stem Cells to Enhance Remyelination in the Treatment of Multiple Sclerosis
Multiple sclerosis (MS) is an autoimmune disease in which the myelin sheath that insulates neurons is destroyed, resulting in loss of proper neuronal function. Existing treatments for MS are based on strategies that suppress the immune response. While these drugs do provide benefit by reducing relapses and delaying progression (but have significant side effects), the disease invariably progresses. We are pursuing an alternative therapy aimed at regeneration of the myelin sheath through drugs that act on an endogenous stem cell population in the central nervous system termed oligodendrocyte precursor cells (OPCs).
Remission in MS is largely dependent upon OPCs migrating to sites of injury and subsequently differentiating into oligodendrocytes – the cells that synthesize myelin and are capable of neuronal repair. Previous studies indicate that in progressive MS, OPCs are abundantly present at sites of damage but fail to differentiate to oligodendrocytes. As such, drug-like molecules capable of inducing OPC differentiation should have significant potential, used alone or in combination with existing immunomodulatory agents, for the treatment of MS. The objective of this project is to identify a development candidate (DC) for the treatment of multiple sclerosis (MS) that functions by directly stimulating the differentiation of the adult stem cells required for remyelination.