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Multi-Million-Dollar Grants for Research in Dementia Striking Younger People
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Projects will help advance research through collaborations and development of novel strategies for frontotemporal dementia
Rochester, Minn. — Mayo Clinic has been awarded two grants for large, five-year projects on frontotemporal dementia (FTD), characterized by degeneration of the frontal and temporal lobes of the brain. While rare, it may strike people in their twenties, even in their teens.
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Duska Anastasijevic, Mayo Clinic Public Affairs, 507-284-5005, Email: newsbureau@mayo.edu
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The projects are funded by the NIH’s National Institute of Neurological Disorders and Stroke (NINDS), National Institute on Aging (NIA) and the National Center for Advancing Translational Sciences (NCATS).
The grants, allocated to the research teams at Mayo Clinic in Rochester, Minnesota and Jacksonville, Florida, cover a wide spectrum of FTD research, to advance their studies aimed at improving the diagnosis and treatment of patients suffering from this disorder.
NINDS has awarded Leonard Petrucelli, Ph.D., chair of the Department of Neuroscience, and his colleagues Kevin Boylan, M.D., Rosa Rademakers, Ph.D., and Dennis Dickson, M.D., a five-year P01 grant to combine their expertise in neurology, genetics, neuropathology and cell biology. The funding will allow researchers to improve understanding of a specific change, or mutation, in the C9ORF72 gene that is the most common cause of FTD and amyotrophic lateral sclerosis (ALS), a neurodegenerative disease that affects the muscles. This will help identify potential biomarkers and therapeutic targets, and develop a biological fluid and tissue resource to aid future drug discovery.
The grant builds on the two groundbreaking discoveries made by neuroscientists at Mayo Clinic in Jacksonville. In 2011, Dr. Rademakers identified an unusual mutation — a short DNA sequence repeated and expanded hundreds to thousands of times — in the C9ORF72 gene. This expanded repeat sequence in the C9ORF72 gene is the most common cause of familial ALS, a major cause of familial FTD, and is also found in people with ALS or FTD who report no family history of either disorder.
In 2013, Dr. Petrucelli uncovered a potentially new therapeutic target and biomarker, termed c9RAN proteins, in ALS and FTD associated with the C9ORF72 repeat expansion. The c9RAN proteins are generated only when the mutation is present making them unique to patients with “c9FTD/ALS.”
“The P01 grant award is a testament to the quality of our patient-driven research, which is enabling our team to identify factors that determine disease severity and potential biomarkers that would be detectable in c9FTD/ALS patients,” says Dr. Petrucelli.
NIA and NINDS also awarded Bradley Boeve, M.D., a neurologist at Mayo Clinic in Rochester, Minnesota with $5,429,913 to conduct a longitudinal evaluation of familial frontotemporal dementia (fFTD) patients. Dr. Boeve and his colleagues will enroll 300 members of families with familial frontotemporal lobar degeneration with changes in genes associated with the disorder. Study participants will undergo annual brain scans, blood and cerebrospinal fluid analysis as well as behavioral and cognitive tests. Dr. Boeve’s team will use that data to identify biomarkers, which will help determine the effectiveness of potential therapies.
“FTD is devastating for affected individuals and their relatives. The features of FTD span dozens of other psychological, psychiatric, medical, and neurologic disorders, so patients often go for months, even years before being properly diagnosed. The research grant recognizes the importance of current efforts to develop treatments for this disorder, particularly in the presymptomatic phase,” Dr. Boeve says.
FTD is the second most common type of dementia in people younger than 65. Approximately 50,000 Americans live with FTD, which is characterized by severe changes in personality, behavior and language due to loss of gray matter in the brain’s frontal and temporal lobes. As the disease progresses, individuals have difficulty planning activities, interacting with others and caring for themselves.
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