Neurodegenerative disorders are the second-leading cause of early-onset dementia, says report

Alzheimer's Drug Discovery Foundation and The Association for Frontotemporal Dementias study identifies funding gaps, opportunities for accelerating drug discovery and development

Neurodegenerative disorders called frontotemporal dementias (FTD) are the second-leading cause of early-onset dementia in persons under age 65 and can emerge sometimes as early as age 20. While research over the past 10 years has contributed much to the understanding of FTD, little progress has been made in the development of effective therapies, says a new report by Alzheimer's Drug Discovery Foundation and The Association for Frontotemporal Dementias.

"Frontotemporal dementias and Alzheimer's disease share some common disease mechanisms and much of what we learn about Alzheimer's can be applied to FTD and vice versa. That is why our two organizations collaborated on this study," says Howard Fillit, MD, Executive Director of Alzheimer's Drug Discovery foundation. "FTD affects a younger population than Alzheimer's, and in some respects is harder to diagnose."

"Over the past 10 years, 74% of funding for FTD has gone to basic research, and only 10% to pre-clinical drug development or toward early detection and diagnosis," says Philip H. Lovett, Research Liaison for The Association for Frontotemporal Dementias' Board of Directors and a Founding Partner of Millennium Partners. "NIH has provided the overwhelming majority of funding, but from 1999 to 2007 its funding has diminished five-fold, and the size of individual grants is smaller."

Alzheimer's disease is typified by plaques of amyloid protein on brain cells, and intracellular tangles of a protein called tau, that affect brain cells in the cerebral cortex and hippocampus, where memories are stored. Some FTD patients also show these tangles of tau, but in the frontal and temporal lobes of the brain that control executive function and higher behavioral functioning. Other FTD patient brains contain aggregates of a newly discovered protein called TDP-43.

"More funding is needed to study biomarkers that differentiate FTD patients with the tau versus the TDP-43 pathologies in order to successfully design clinical trials," says Dr. Fillit. "We now know much more about diseases at the molecular level, and can identify the targets, or biological components, for drug discovery. Drug development could be accelerated by more investments in novel technologies, such as PET imaging, for early detection and diagnosis."

"Charitable philanthropies and foundations have partially offset the decrease in NIH funding," Mr. Lovett says. "But there are many drug discovery programs that would benefit from modest sums - and here is where foundations can make a significant impact on drug strategy."

Recent studies estimate the average cost of developing a single drug to be $1.3 billion to $1.7 billion. The process can take 10 to 15 years, through the stages of discovering targets, validating leads, pre-clinical development, and clinical trials. For every 5,000 to 10,000 compounds that enter the drug development pipeline, only 250 will progress to pre-clinical development as leads; five will move forward into first-in-man studies - of which only a single compound will become an approved drug. Because FTD is a relatively rare disease, drug discovery and research can be expedited through provisions in the Orphan Drug Act.

While the first symptom of Alzheimer's is memory loss, the first symptom of FTD can be a change in personality. Forms of frontotemporal dementias include behavioral variant FTD (behavioral disorders), corticobasal degeneration (movement disorders), motor-neuron disease, Pick's disease, progressive aphasia, semantic dementia, and progressive supranuclear palsy.