Miller School Investigators Receive Grant Awards for Alzheimer’s Research and Treatment

The University of Miami Miller School of Medicine has been awarded more than $900,000 in grant awards from the Florida Department of Health to be used for projects supporting research leading to the prevention or cure of Alzheimer’s disease.

“On behalf of all University of Miami School of Medicine investigators, we would like to thank the Ed and Ethel Moore Alzheimer’s Disease Research Program for its support,” said David Loewenstein, Ph.D., Carlos Moraes, Ph.D., and Claes Wahlestedt, M.D., Ph.D., in a combined statement.

“This funding will support our work in identifying the earliest manifestations of Alzheimer’s disease through novel cognitive and neuroimaging modalities. We will also examine basic aspects of the disease through discovery of molecular biomarkers, studies of gene expression and possible drug treatments to address critical aspects of patient care.”

The grant awards are the result of the new $3 million initiative passed during the 2014 legislature and signed into law by Governor Rick Scott. Funding is provided through the Ed and Ethel Moore Alzheimer’s Disease Research Program that supports research for better prevention, diagnoses, treatments and cures for Alzheimer’s disease.

“Today is a great victory for the individuals and their families who are battling this terrible disease,” said Gov. Scott. “With our $3 million investment in Alzheimer’s prevention and treatment research, the awarded organizations can begin to provide hope for the many individuals and their families whose lives are affected by Alzheimer’s. We look forward to seeing the success of these projects and will continue to focus on enhancing Florida’s developing research community.”

Wahlestedt, with Claude-Henry Volmar, Ph.D., and other colleagues at the Center for Therapeutic Innovation, will use the state funding to advance a project with unique new drug molecules that have already shown great promise in a variety of cell and animal models for Alzheimer’s disease. The objective is to identify an optimized drug candidate that will eventually be used in a clinical trial in human patients.

“The project builds upon a so-called epigenetic approach where a single drug would simultaneously affect the expression of a number of defined Alzheimer’s disease-related drug targets. This should be advantageous over conventional drug therapies, which involve affecting a single drug target — arguably an oversimplified strategy that has unfortunately failed repeatedly in a wide range of clinical trials,” said Wahlestedt, Leonard M. Miller Professor, Associate Dean for Therapeutic Innovation, Vice Chair for Research in the Department of Psychiatry and Behavioral Sciences, and Director of the Center for Therapeutic Innovation.

Loewenstein, professor of psychiatry and behavioral sciences, and a member of UM Center on Aging faculty, said his team will be leading a four-institution consortium at UM that also includes the University of Florida, Florida International University and Mount Sinai Medical Center. The consortium will determine if sensitive and novel new cognitive measures can detect Alzheimer’s disease in its earliest stages.

“We will also examine the relationship of these new measures to amyloid burden on PET scans, structural changes on MRI and new MRI water-based measures of inflammation and genetic markers,” said Loewenstein. “This consortium will provide a platform for the use of other Florida institutions in merging complex neuroimaging data, to develop common testing protocols and in building a common database. We believe that this work will help to position us as leaders in earlier diagnoses that will allow for more effective and novel interventions.”

Moraes, professor of neurology and cell biology, and holder of the Esther Lichtenstein Chair in Neurology, said that the Molecular Bioenergetics Laboratory will use unique genetically modified mice to define the role of mitochondrial dysfunction in the development of Alzheimer’s disease pathology. In the last decade, the group has developed mouse models with defects in specific mitochondrial respiratory chain enzymes that are key to the production of energy in the brain.

“Although defects in these enzymes have been reported in brains of patients with Alzheimer’s disease, the causative role of such defects could not be directly tested. Our lab will combine the genes that cause mitochondrial defects with genes that cause Alzheimer’s pathology in a single mouse and study the consequences to brain pathology,” Moraes said.