Mayo scores major dementia grants

After more than a decade of work on what's been called "the most common disease no one has ever heard of" — frontotemporal dementia — Mayo Clinic has been chosen to participate in a set of federal research projects that could help unlock a broad set of related brain disorders, including Alzheimer's disease.

The grants, announced by the National Institutes of Health (NIH), are designed to improve science's understanding of diseases that kill cells in the brain's frontal region, which controls executive functioning, and in the temporal region, which controls speech, language and memory. NIH awarded $5.9 million to fund the first year of three five-year projects.

Frontotemporal Degeneration (FTD) is a fatal disorder that affects at least 50,000 people in the United States — perhaps many more — and causes such profound personality changes that it often is misdiagnosed as a psychiatric disorder. Researchers have traced it to proteins ­accumulating in the brain, leading to cell death, which may also be at the root of Parkinson's disease, Alzheimer's and amyotrophic lateral sclerosis (ALS), among other diseases.

"What is really striking is that four major grants have now been funded in [this] area, which is tens of millions of dollars [over five years]," said Dr. Brad Boeve of Mayo Clinic, one of the nation's leading FTD researchers and principal investigator for one of the new grants. "It's just great to see the attention attached to FTD that it so aptly deserves," he said.

Mayo Clinic in Rochester will get nearly $3.4 million to set up a registry of 300 patients and their family members with genetic mutations associated with FTD to better understand the "natural history" of the disease.

Mayo Clinic in Jacksonville, Fla., will get nearly $1.3 million to investigate the breakdown of a gene known to be the most common cause of both FTD and ALS, or Lou Gehrig's disease, a fatal neurodegenerative disorder that short-circuits the muscles.

In addition, the ­University of California in San Francisco, a leading FTD research institution, will get $1.25 million to establish a consortium aimed at improving clinical trial designs and developing new treatments for FTD and related disorders. Earlier this month, NIH also announced an award of $6.24 million to establish a Rare Diseases Clinical Research Consortium that will study chromosome mutations in ALS and FTD.

Boeve said the grant recipients have been working collaboratively for a decade or more. The establishment of an FTD registry is important because it will create an open, worldwide network for those afflicted by the disease. A registry also is attractive to the pharmaceuticals industry, he said.

"We've been hearing this forever, frankly: 'Oh, these diseases are so rare, why is any drug company going to get interested in focusing their attention to solving it?' But now they are showing interest, which is fantastic," said Boeve, who just returned from the ninth International Conference on Frontotemporal Dementias, in Toronto.

Industry wants assurances that if it spends tens of millions of dollars on dementia research that it will have enough subjects to recruit for drug studies, Boeve said. "And so, by having a registry of interested, motivated people, then we can say, 'Look, we have these people.' "

Boeve's research will focus on the three most-common genes associated with FTD, which also can occur randomly. He expects to recruit 100 participants who have been found to have the disease, plus 100 family members that have genetic mutations but show no symptoms yet, and another 100 who have neither the mutation nor any symptoms.

The project aims to establish the natural history of the disease to determine the likelihood of developing symptoms. Without knowing that, it's impossible to tell if a prospective drug is preventing or delaying the onset of the disease, Boeve explained.

Genetic mutations account for 15 to 40 percent of FTD cases, according to the Association for Frontotemporal Degeneration. That makes it easier to study than most Alzheimer's cases, which likely results from a combination of genetic mutations, environmental and lifestyle factors. The diseases do share common traits, however.

"The central theme in all of these neurodegenerative disorders is protein disregulation — clumping in the neuron and/or glia [cells that support or protect neurons]," Boeve said.

"The expectation is this won't be just a five-year grant," he added. "This may be 10, 15, 20 years, so that we'll be able to prevent this completely — eventually."