Two UCSF scientists have been selected for the American Academy of Neurology’s prestigious Potamkin Prize, for their “outstanding achievements” in research on dementias.

Bruce Miller, MD, W. & Mary Margaret Clausen Distinguished Professor of Neurology, and Lennart Mucke, MD, Joseph B. Martin Distinguished Professor of Neuroscience and director of the Gladstone Institute of Neurological Disease, will receive the honor for their major contributions to the understanding of the causes of, and treatment strategies for, frontotemporal lobar degeneration, Alzheimer’s disease and related diseases.

Bruce Miller, MD

Bruce Miller, MD

Lennart Mucke, MD

Lennart Mucke, MD

They will receive the prize on April 15, 2010 at the AAN’s annual meeting. The $100,000 prize is to be used for continuing research on dementias.

As director of UCSF’s Memory and Aging Center, Miller oversees a program that provides clinical care and conducts clinical research on all forms of dementia. The Center carries out neuroimaging studies aimed at improving diagnoses of the various forms of dementia, understanding the progression of the diseases and studying the impact of experimental drugs on the conditions.  For more than a decade, he and Mucke, a basic researcher based at the Gladstone Institutes, have worked closely to build one of the premier dementia research programs in the world.

Miller has a special interest in the behavioral effects of dementia, notably those seen in FTLD, once commonly known as Pick’s disease. Along with Alzheimer’s disease, FTLD is the leading cause of dementia in patients under 65 years.

FTLD presents as several forms—behavioral FTLD is characterized by emotional deficits, impulsivity and a lack of empathy; semantic dementia is marked by a gradual loss of the meaning associated with words; and progressive non-fluent aphasia is impacts patients’ production of language.

Patients with the behavioral form of the disease frequently exhibit unexpected artistic and musical talents that may initially intensify as the disease progresses, a phenomenon that Miller has documented. This trait is attributed to the strengthening and remodeling of parts of the brain linked to creativity, compensating for damaged areas associated with language.

When Miller started studying FTLD more than 25 years ago, the mantra in neurology was “Don’t pick Pick’s disease,” he says. At the time, the disease was viewed as a “rare, biologically obscure illness that could not be diagnosed at the bedside.”

Today, thanks in part to Miller and colleagues’ pioneering research, neurologists are able to distinguish FTLD from Alzheimer’s disease in its earlier stage. Promising advances have been made in the genetics and molecular pathology of the disorder. Recent developments include testing therapies that target the genetic cause for FTLD, a milestone that Miller describes as “the most exciting work” he has ever undertaken.

Author of the book “The Human Frontal Lobes” and the medical director of the John Douglas French Foundation for Alzheimer’s Disease, Miller works closely with UCSF Nobel laureate Stanley Prusiner, MD, director of the UCSF Institute for Neurodegenerative Diseases and, himself, the 1991 recipient of the Potamkin Prize. In the early 2000s, they conducted a clinical trial using an experimental drug to treat the dementia known as Creutzfeldt-Jakob disease (CJD).

Prusiner won the Nobel Prize in Physiology or Medicine in 1997 for his discovery of prions, a class of proteins that causes CJD in humans and “mad cow” disease in cattle. The discovery has informed research into the role of misprocessed proteins in more common brain diseases, including Alzheimer’s and Parkinson’s disease.

Mucke, a basic researcher, is best known for his role in instigating a turnaround in the direction of research into Alzheimer’s disease, from an almost exclusive focus on morphological abnormalities in the brain to a focus on the molecular processes that cause the dysfunction of neural networks in the brain.

Ten years ago, many scientists believed the condition was caused by the accumulation of amyloid plaques in the brain. Mucke and colleagues showed that a minuscule constituent of these plaques, known as amyloid-beta peptide, can disrupt the function of brain cells independent of plaques, thus narrowing the whereabouts of the disease culprit from the “haystack” to the “needle.”

Mucke has also generated genetically engineered mice to pinpoint the key molecules and proteins that contribute to the progression of Alzheimer’s thereby setting the stage for new therapies to combat the disease. Using mouse models of Alzheimer’s disease, Mucke and colleagues have successfully prevented the disease progression and even reversed cognitive impairments.

The Potamkin Prize, says Mucke, is a wonderful reinforcement of the synergism” between himself and Miller. “Working hand-in-hand, we have developed innovative translational programs for the investigation and treatment of dementia and related disorders.”

Miller concurs, describing the Potamkin Prize as “the highlight of my academic career.”

The Gladstone Institutes is a nonprofit, independent research and educational institution, consisting of the Gladstone Institute of Cardiovascular Disease, the Gladstone Institute of Virology and Immunology and the Gladstone Institute of Neurological Disease. Independent in its governance, finances and research programs, Gladstone shares a close affiliation with UCSF through its faculty, who hold joint UCSF appointments.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.