Stem cell research funding leading to clinical trials
Game-changing grants focus on Huntington's disease, critical limb ischemia and oesteoporosis
Posted Jan. 2, 2013
Mike Hinshaw was 27 years old when he found out that the father he had not seen since he was a young child was dying of Huntington’s disease. The inherited disorder that kills brain cells, leading to severely erratic muscle movements and psychiatric symptoms, typically strikes affected patients in their 30s, leading to death 10 to 20 years later. Testing confirmed that Hinshaw inherited the abnormal gene.
“Our doctor basically told us to go home and wait to die, that there was nothing anyone could do,” recalled Katie Jackson, Hinshaw’s wife. “Fortunately, the Huntington’s Disease Society of America referred us to the HDSA Center of Excellence at UC Davis.”
There, Hinshaw and Jackson found a different world from the one in which Hinshaw received his diagnosis — one of physicians, nurses and basic scientists who brimmed with infectious optimism as they actively worked toward finding a cure for Huntington’s.
In July 2012, reason for optimism grew, as the California Institute for Regenerative Medicine (CIRM) granted UC Davis researchers $53 million in competitive awards to advance stem cell therapies and bring them to Phase I clinical trials. Of that, nearly $20 million was earmarked for Huntington’s disease.
A promising new therapy
Vicki Wheelock, clinical professor of neurology and director of the HDSA Center of Excellence at UC Davis, and Jan Nolta, director of the UC Davis Institute for Regenerative Cures, are leading a team of investigators to prepare the first FDA-approved cellular therapy for patients with Huntington’s disease.
Huntington’s disease affects about 1 in 10,000 people in the U.S. The financial burdens are in the billions; the emotional costs are immeasurable; and there is no cure. This very generous grant represents an important turning point in our efforts to overcome this disease.
— Vicki Wheelock
The treatment involves infusing stem cells that are customized to secrete a factor to restore brain cells damaged by the mutant protein that is the hallmark of the disease. The therapy is effective in animal models of Huntington’s.
“Huntington’s disease affects about 1 in 10,000 people in the U.S.,” says Wheelock. “The financial burdens are in the billions; the emotional costs are immeasurable; and there is no cure. This very generous grant represents an important turning point in our efforts to overcome this disease.”
Restoring circulation to legs and feet
More than 1 million people in the U.S. suffer from critical limb ischemia, the most severe form of peripheral artery disease. The disease results in reduced blood flow to the legs, leading to pain and sometimes foot ulcers, gangrene, amputation and death.
Nolta and John Laird, professor of cardiovascular medicine and director of the UC Davis Vascular Center, received a $14.1 million CIRM grant to launch human clinical trials to test stem cell therapies for this painful and debilitating disease.
The team will use mesenchymal stem cells, from healthy bone marrow donors, that are bioengineered to produce a revascularizing factor. When injected into the legs of patients with critical limb ischemia, the cells are expected to migrate to low oxygen areas.
“We’ve seen that the special growth factors produced by our engineered stem cells can rapidly restore blood flow in the limbs of animal models that had no leg circulation whatsoever,” says Laird.
“Our CIRM grant now enables us to focus on finalizing safety and efficacy tests for humans so we can move this candidate therapy into clinical trials that will hopefully save people from amputation.”
New paradigm for treating oestoporosis
Osteoporosis, the most common bone disease, is expected to affect more than 61 million Americans by the end of this decade. Usually caused by estrogen deficiency and aging, the disease results in loss of bone density, making patients susceptible to debilitating fractures.
A team of researchers, led by Nancy Lane, professor of internal medicine and holder of the endowed chair for Healthy Aging and Geriatrics, has received a $20 million grant from CIRM to refine a stem cell therapy for osteoporosis and test its effectiveness in men and postmenopausal women. The therapy involves using a small molecule that the team developed to direct a patient’s own mesenchymal stem cells to the surface of bone, where they can grow new bone tissue.
“The only currently approved therapy for osteoporosis that increases bone formation requires costly and inconvenient daily injections for two years,” says Lane. “I’m very optimistic that we will be able to successfully and fairly quickly develop a bone-building treatment for osteoporosis that is much more patient-friendly.”
Fostering the future of stem cell research
In addition to the grants aimed at bringing promising treatments to clinical trials, CIRM recently awarded a $264,000 grant to UC Davis Health System to support internships for high school students. Each summer over the next three years, 10 students will be invited to work alongside scientists and research technicians. The program will enable promising students to gain college-level experience and potentially inspire them to pursue science degrees and careers.
“I am inspired to see such enthusiasm, talent and novel ideas in young people when they have an opportunity to work in one of our labs,” says Nolta. “The students who will intern at UC Davis represent a very bright future for advancing science and achieving breakthrough discoveries, particularly, I hope, in the area of stem cell treatments and cures.”
UC Davis is playing a leading role in regenerative medicine, with more than 150 scientists working on a variety of stem cell-related research projects. The UC Davis Institute for Regenerative Cures, a $62 million facility supported by CIRM, opened in 2010 on the Sacramento campus and includes Northern California’s largest academic Good Manufacturing Practice laboratory. UC Davis also has a Translational Human Embryonic Stem Cell Shared Research Facility in Davis and a collaborative partnership with the Institute for Pediatric Regenerative Medicine at Shriners Hospital for Children Northern California.
For patients like Mike Hinshaw and their families suffering from chronic disease or injury, the promise of stem cell therapies has been invaluable.
“Dr. Nolta’s program has brought us from hopelessness to hope,” says Hinshaw. “It has totally changed our lives.”