In what scientists and patients advocates say is an exciting development in the area of Huntington's disease (HD) research, California's stem cell agency today approved a grant proposal worth nearly $20 million that is designed to propel researchers at UC Davis Health System toward preparing for the first FDA-approved cellular therapy for HD patients. The researchers plan to use a novel therapy that could restore the health of brain cells damaged by a hallmark of the devastating neurodegenerative disease, the mutant huntingtin (htt) protein.
With a green light from the governing board of the California Institute for Regenerative Medicine (CIRM), Vicki Wheelock, clinical professor of neurology and director of the HDSA Center of Excellence at UC Davis, and Jan Nolta, professor of internal medicine and director of the UC Davis Institute for Regenerative Cures, are leading a research project that plans to infuse specially engineered mesenchymal stem cells into the brains of Huntington's disease patients. The stem cells, which will be customized to secrete brain-derived neurotrophic factor (BDNF), are expected to restore the health of brain cells damaged by the mutant htt protein. This therapy has been shown to be effective in animal models of HD.
"About 1 in 10,000 Californians has Huntington's disease," said Wheelock. "It touches all races and socioeconomic levels. The financial burdens are in the billions, the emotional costs are immeasurable, and right now there is no cure. Our CIRM grant enables us to greatly accelerate our work toward developing a safe and effective cellular therapy for Huntington's disease. As a physician who has witnessed the tragedy of this illness over and over again, I know that this very generous grant represents an important turning point in our efforts to overcome this disease. The award gives us the hope of developing a disease-modifying treatment for HD and the optimism of finding a cure."
Huntington's disease is an inherited disorder passed down through families in which brain cells waste away, or degenerate. While most patients develop symptoms as adults, children and teens can develop juvenile HD. Movement, judgment, thinking and speech decline, and the associated psychiatric symptoms can be very disabling. Over the course of the disease, patients suffer painful involuntary movements and loss of independence. Many people who are at risk are reluctant to be tested for fear they may lose health insurance or their jobs, and families of HD victims face the added challenges and costs of long-term caregiving.
The planned UC Davis trial for treating HD will target earlier phases of the disease, when patients are younger and before the illness's full impact takes its toll. Wheelock said that mesenchymal stem cells represent remarkably effective delivery vehicles because they move well through tissue and can produce high levels of growth factor for uptake by the damaged neurons. In preparation for its phase I clinical trial with HD patients, the Huntington's disease team is carefully testing its proposed cellular infusion therapy for safety and effectiveness.
"The delivery of brain-derived neurotrophic factors via mesenchymal stem cells significantly reduces behavioral deficits in HD mice back to nearly normal levels," said Nolta, who has been working with Wheelock for the past several years in conducting the research for their successful grant proposal to CIRM. "We are doing further work to ensure that the proposed therapy will be safe and effective as we prepare for a clinical trial."
For patients and their families, who have been tireless advocates for stem cell research, a multimillion dollar grant and the promise of a phase I clinical trial are breakthrough accomplishments in the fight to overcome Huntington's disease.
"It's hard to put into words what this stem cell funding truly means for families like mine," said Judy Roberson, who lost both her 51-year-old husband and brother-in-law to the disease, and then went on to provide the impetus for establishing a multidisciplinary HD clinic at UC Davis. "The determination and dedication of Dr. Wheelock and Dr. Nolta, combined with CIRM's support, gives us the edge we need to overcome this terrible disease."
Roberson and other patient advocates helped provide funding support to UC Davis at a crucial point in the university's stem cell research for HD. Also, a pilot grant from the university's Clinical and Translational Science Center, along with donations from two non-profit organizations - Team KJ and the Deshalamar Foundation - enabled Wheelock and Nolta to conduct the preliminary biosafety studies that were needed before the state stem cell agency would consider their Disease Team grant proposal. Generous private philanthropy from the Roberson and Charles Pue families provided early support to the HD clinic at UC Davis, which is now a hub for clinical care and research trials and has followed over 300 patients with the disease.
To develop the proposed therapy to be used in the clinical trial, basic scientists and clinicians who comprise the Huntington's disease team have met weekly for the past several years. Nolta noted that the team taps into expertise from throughout UC Davis, including the university's health system leadership, led by Claire Pomeroy, vice chancellor for Human Health Sciences and dean of the School of Medicine, and Fred Meyers, the school's executive associate dean. Wheelock credited her team's membership in the Huntington Study Group for developing expertise in conducting human HD research studies.
The HD researchers also benefit from collaboration with the California National Primate Research Center in Davis; UC Davis Good Manufacturing Practice facility; UC Davis Clinical and Translational Science Center, UC Davis Center for Imaging; and UC Davis Department of Neurology.
"We are also consulting with national and international Huntington's disease experts," said Nolta. "But most importantly, the Huntington's disease community and patient advocates, who already have helped us make great strides through their philanthropy and participation in observational clinical trials, will continue to provide incredible inspiration for all of us who are working to treat this heartbreaking disease."