Two physician-scientists in search for better Alzheimer's disease treatment

University of California, San DiegoJun 27 2015

Two of the nation's leading physician-scientists in the search to better understand and treat Alzheimer's disease - William Mobley, MD, PhD, and Michael Rafii, MD, PhD - have been named interim co-directors of the Alzheimer's Disease Cooperative Study (ADCS), a major initiative formed in 1991 as a cooperative agreement between the National Institute on Aging (NIA) and the University of California, San Diego.

The selection was made in collaboration with the NIA.

Mobley is chair and Distinguished Professor in the Department of Neurosciences in the UC San Diego School of Medicine. Rafii is assistant professor of neurosciences and ADCS' medical director. They will serve as co-directors during a national search for a new permanent ADCS director, replacing Paul Aisen, MD, who resigned his faculty position at UC San Diego School of Medicine and position as ADCS director, effective June 21.

"We appreciate Dr. Aisen's eight years of service to ADCS and wish him well," said David Brenner, MD, vice chancellor, UC San Diego Health Sciences and dean of UC San Diego School of Medicine. "The selection of Drs. Mobley and Rafii represents an exciting new direction for ADCS. This is a moment of terrific opportunity, a chance to expand, innovate and write a new and bolder chapter, such as development of more creative clinical trial designs."

"In recent years," Brenner said, "there have been dramatic advances in our understanding of Alzheimer's disease (AD). We are on the cusp of creating effective treatments that may, in time, lead to preventing this terrible neurodegenerative scourge. A good deal of this progress is due to the amazing efforts and talents of UC San Diego scientists, doctors and staff. Their outstanding work continues. It is growing, accelerating - and it remains fully and enthusiastically supported by the university and by the AD community."

For example, Brenner noted future plans could include relocating ADCS into the new seven-story, $269 million Altman Clinical and Translational Research Institute (CTRI) building rising next to the Jacobs Medical Center at UC San Diego Health System, also opening in 2016. The building will include multidisciplinary clinical facilities and a new state-of-the-art research MRI to image the brain in clinical trials.

"Integrating the ADCS into the medical center research community from its current off-campus site," said Gary S. Firestein, MD, CTRI director, dean and associate vice chancellor of translational medicine, "would create enormous opportunities with greater collaboration and improved access to laboratory and imaging resources, patients and clinical services."

The ADCS was founded by the late Leon Thal, MD, a world leader in Alzheimer's research, to promote the discovery, development and testing of new drugs for the treatment of AD. It is part of a larger AD research and treatment effort at UC San Diego, which includes the Shiley-Marcos Alzheimer's Disease Research Center, under the direction of Douglas Galasko, MD, and Edward Koo, MD; the Memory Disorders Clinic, headed by Rafii; and the Memory, Aging and Resilience Clinic, a novel center that offers comprehensive cognitive, emotional and physical health evaluations of older adults.

Interim co-directors Mobley and Rafii bring particular experience and expertise to their new roles. Mobley is among the nation's most prominent academic neurologists. He is executive director of the Down Syndrome Center for Research and Treatment. Persons with Down syndrome, a genetic disorder, are predisposed to develop AD, and by age 40, virtually all individuals with Down syndrome have the pathology of AD in their brains.

Rafii is principal investigator on numerous AD studies at UC San Diego, including Scarlet Road, an on-going, multi-year, multi-institution study to assess the effects of gantenerumab, an antibody-based drug shown to attack and remove beta-amyloid plaques in animal models. Rafii also is clinical director of the Down Syndrome Center and oversees interventional clinical trials of resveratrol—a compound found in red grapes, chocolate and tomatoes—in patients with mild to moderate dementia due to AD.

Clinical trials like these are powered by basic research. In 2012, for example, a team of UC San Diego School of Medicine scientists and others, led by Larry Goldstein, PhD, Distinguished Professor in the departments of Neuroscience and Cellular and Molecular Medicine and director of both the UC San Diego Stem Cell Program and Sanford Stem Cell Clinical Center, created the first stem cell-derived, in vitro models of sporadic and hereditary AD using induced pluripotent stem cells from patients with the disease.

This year, Goldstein and colleagues identified a gene variant that may be used to predict people most likely to respond to an investigational therapy under development for AD. The work is based on experiments with cultured neurons derived from adult stem cells.

Meanwhile, Mark Tuszynski, MD, PhD, director of the Center for Neural Repair at UC San Diego School of Medicine, and colleagues are investigating the use of growth factors delivered by gene therapy to the brain to preserve neuronal survival and cognitive function and forestall the effects of AD. Some of this work has entered later stage clinical trials.

"The depth and breadth of AD research at UC San Diego is without parallel," said Brenner. "Our faculty, programs and centers have been grappling with the enigma of Alzheimer's disease for decades. We have a history of achievement. Change is an opportunity to develop a much stronger and more forward-thinking program. We are committed to a bright future for ADCS at UC San Diego - and to improving the lives of millions of Americans who have or might develop AD."