Planning awards advance new therapies for Huntington's disease, critical limb ischemia, airway disease, HIV/AIDS and osteoporosis
The California Institute for Regenerative Medicine (CIRM), the state stem cell agency, today approved research planning grants for five UC Davis Health System teams that are working to develop human clinical trials to treat illnesses such as Huntington's disease, vascular disease, osteoporosis, HIV/AIDS and airway disease in children. The awards are specifically designed to support collaborative research that will bring potential therapies to the Food and Drug Administration for approval within four years.
"These grants are extremely important to California and to the field of regenerative medicine," said Jan Nolta, professor of internal medicine and director of the UC Davis Institute for Regenerative Cures. "They enable our teams of scientists and clinicians to plan stem cell clinical trials that will offer treatments to patients who currently have few if any other medical options."
Stem cells offer the unique potential to restore tissue and repair damage caused by injury or disease. Developing new therapies can normally take 12 or more years. CIRM funding helps advance the most promising approaches for early phase clinical trials. Today's grants, which range from $71,000 to $110,000, are the first in a two-step process toward applying for full research awards that will be available early next year and worth up to $20 million each.
Known as Disease Team Therapy Development Awards, the grants went to UC Davis stem cell research teams working on five different health disorders:
Huntington's disease: Nolta and Vicki Wheelock, clinical professor of neurology and director of the UC Davis Huntington's Disease Clinic, lead a team preparing for a phase I clinical trial using adult stem cells to treat people with the devastating neurodegenerative condition of Huntington's disease. Study participants will receive stem cells known as mesenchymal stem cells, which are derived from a healthy donor's bone marrow. These stem cells will be engineered to secrete a neural growth factor, which the UC Davis team believes will have restorative effects by encouraging new neurons to develop in the brains of Huntington's disease patients.
Critical limb ischemia: People with poor circulation, often caused by diabetes, and facing the risk of amputation, will benefit from the work of a team led by John Laird, director of the UC Davis Vascular Center. The group is developing specially engineered mesenchymal stem cells to treat critical limb ischemia -- a condition occurring when blood flow to the feet or legs is restricted. This clinical trial will use donor stem cells that have been engineered to secrete the same vascular growth factor needed to form new blood vessels following an injury or when vessels have been blocked. The stem cells are expected to migrate into low-oxygen tissue areas, where they will wrap around damaged blood vessels and help restore circulation.
Severe airway obstruction in children: Pioneering throat surgeon Martin Birchall and stem cell scientist Alice Tarantal are developing an innovative tissue-engineering therapy for children suffering from severe airway obstruction, an extraordinarily difficult-to-manage and life-threatening condition that affects approximately 200 children a year in California. The team plans to use a patient's own stem cells -- in this case stem/progenitor cells -- to create a bioengineered airway that can be implanted to reverse the obstruction. Birchall, who was a part of the surgical team at UC Davis that performed the world's second-documented larynx transplant last year, says that bioengineered airways using a patient's own stem cells -- known as an autogolous transplant -- would not require lifelong, harmful anti-rejection medications and could be used for people of all ages, including those with chronic obstructive pulmonary disease.
HIV/AIDS: Another CIRM award is going to the UC Davis disease team investigating a unique stem cell gene therapy for HIV. Led by Mehrdad Abedi, a professor of hematology and oncology, and Gerhard Bauer, director of the UC Davis Good Manufacturing Practice facility, this clinical trial will use an individual's own blood-forming, or hematopoietic, stem cells that have been genetically modified to express three different anti-HIV genes. Because blood-forming stem cells have the ability to self-renew, the team believes that this treatment will enable a patient's immune system to be repopulated with HIV-resistant cells after transplantation. Abedi and Bauer say this stem cell-based therapy may require only a single treatment to cure an HIV-infected individual.
Osteoporosis: Nancy Lane, professor of internal medicine and director of the UC Davis Musculoskeletal Diseases of Aging Research Group, leads a team targeting osteoporosis -- the debilitating disease affecting an estimated 10 million Americans. Lane's group is developing a clinical trial to test a synthetic molecule that has been engineered to direct transplanted mesenchymal stem cells to the surface of bones, helping create new bone formation. A successful therapy would help address the many problems associated with osteoporosis, in which bones become thin, weak and brittle and break more easily, especially in women over the age of 50.
"Our goal is to provide better options for people who have incurable genetic disorders like Huntington's disease or whose disease has progressed beyond the capabilities of our best medical practices, like critical limb ischemia and osteoporosis," said Nolta, who added that UC Davis currently has several small, stem cell clinical trials already under way. "Regenerative medicine offers new hope, and today's planning grants represent a crucial step in being able to turn stem cells into cures."