UCSF scientists have received two grants from the California Institute for Regenerative Medicine to refine their human embryonic stem cell-based strategies for treating neurological diseases and liver failure. The goal of the grants is for researchers to make significant strides toward the development of potential therapies within the next three years.
If the strategies prove successful, they could then be further prepared as potential therapies and submitted as new drug applications to the U.S. Food and Drug Administration, leading toward clinical trials.
One team, led by Arturo Alvarez-Buylla, PhD, UCSF Heather and Melanie Muss Professor of Neurological Surgery, received a $1,752,058 grant to further investigate their novel strategy using embryonic neurons to inhibit the hyperactivity that occurs in the nervous system in several neurological conditions. Maintaining the balance between inhibitory and excitatory signaling in the nervous system is critical to normal neurological function.
The research supported by the grant will focus on epilepsy, but potentially could be used to treat Parkinson’s disease, traumatic brain injury, and spasticity after spinal cord injury.
“In 20 to 30 percent of patients with epilepsy, seizures are unresponsive to drugs, requiring invasive surgical resection of brain regions with aberrant activity,” says Alvarez-Buylla.
“The candidate cells we propose to develop can inhibit hyperactive neural circuits after implantation into the damaged brain. These cells have the unique ability to disperse through the adult brain and become functionally integrated in the neural circuitry. By bringing back a balance between excitation and inhibition in the nervous system, these cells could have important therapeutic benefits.”
Another team, led by Mark Zern, MD, of University of California, Davis, includes UCSF co-principle investigator Holger Willenbring, MD, assistant professor of surgery. The scientists will use their $5,199,767 grant to develop therapeutically effective liver cells, or hepatocytes, from human embryonic stem cells.
“Previous studies have shown that human embryonic stem cell-derived hepatocytes can provide liver function in rodents,” says Willenbring. “We will be seeking to produce human liver cells that stand the test of curing a mouse model of human liver failure, with an eye toward clinical application.”
“The cells could be used in patients suffering acute liver failure and those requiring such large liver resections that the residual hepatocyte mass wouldn’t be able to provide enough liver function until natural regeneration had occurred.”
The projects are among the 19 “translational research” awards announced yesterday by CIRM. The projects are expected to either result in a proposed drug or cell therapy or lead to significant progress in the development of a potential therapy, which could then be further developed for submission to the FDA for clinical trial.
Source: Jennifer O’Brien
University of California — San Francisco