NEW YORK--(BUSINESS WIRE)--CurePSP, the foundation for prime of life neurodegeneration, has issued four Venture Grants totaling $300,000 for research in progressive supranuclear palsy (PSP) and the related disease, corticobasal degeneration (CBD). The studies will investigate the mechanisms of toxic tau protein aggregation in the brain.
Tau is a normal brain protein that, when folded on itself in an abnormal way, forms clumps called neurofibrillary tangles that are toxic to some types of brain cells. In the cases of PSP and CBD, the brain cells involved are important in the control of movement, behavior, and thinking. Unlike many other disorders of tau aggregation, PSP and CBD are pure tauopathies, which means that no other proteins are clumping along with tau. This makes these disorders good subjects for studying the pathology involved in many other and often more common neurodegenerative conditions, including Alzheimer’s disease, which afflicts some six million people in the U.S. alone.
Lawrence I Golbe, MD, CurePSP Director of Scientific Affairs, said, “We are pleased to be able to fund these talented investigators whose studies will advance our understanding of the key role that tau protein aggregation plays in neurodegeneration.”
The grants will fund the following studies:
Lukasz Joachimiak, The University of Texas Southwestern Medical Center, Dallas
The Mary Jane Semcer Legacy Study
Structural basis for tau strain conformation in CBD and PSP
In the brain, the tau protein can form an altered shape that clumps together in an aggregated form. This study will isolate the tau protein from healthy PSP and CBD patient brain tissues. Specialized research tools will be applied to determine how the abnormally folded shape of tau differs from the tau from healthy brains. Understanding the fine details of how the tau protein changes from a normal shape to the different “bad” forms found in disease will provide the blueprint for designing new methods to detect and prevent these devastating diseases in patients.
David Butler, Neural Stem Cell Institute, Rensselaer, NY
Bifunctional intrabodies to lower tau
The goal of this project is to develop therapeutic agents that will prevent tau accumulation and associated death of brain cells with novel antibody-based reagents (termed intrabodies). Intrabodies are antibodies expressed within brain cells, while antibodies produced by the immune system or administered by vein do not penetrate brain cells. These antibodies are highly selective for tau, and they have been engineered to target tau for degradation using the cell’s normal clearing process. The study’s central hypothesis is that targeted degradation of tau protein will reduce the amount of tau available to misfold and thus reduce cell death.
J. Mark Cooper, University Hospital, London
The influence of TRIM11 on tau, aggregation, release, and propagation
This study will investigate the effects of a protein known as TRIM11 on toxic tau protein aggregation in the brain. TRIM11 is believed to play a role in regulating the levels of some proteins within the cell, in particular proteins that may form aggregates. To identify how changes to TRIM11 may influence PSP, the study will use models of brain cells grown in the laboratory to focus on how changes to TRIM11 influence tau protein regulation, in particular, its tendency to aggregate. These findings may help to identify potential therapeutic targets to modify PSP disease progression.
K. Matthew Scaglione, Duke University, Durham, NC
Small-molecule regulation of a protein quality-control E3 to treat PSP
The protein Hsc70, or CHIP, accelerates the removal of tau from the brain. This project intends to identify compounds that stimulate CHIP functions. One important such function is as an E3 enzyme, which is an important part of one of the brain cells’ “garbage disposal” mechanisms called the ubiquitin-proteasome system (UPS). E3 allows the UPS to recognize specific proteins for appropriate disposal. Finding new compounds to stimulate this function is an important first step toward developing small (that is, orally dosable) molecules to slow or prevent the progression of PSP and CBD.
CurePSP’s Venture Grants program provides seed funding for early-career investigators who want to test their innovative ideas. Grant applications are reviewed by CurePSP’s eminent international Scientific Advisory Board (SAB) chaired by Dr. Golbe. CurePSP’s Venture Grants program is one of the few sources of funding for early stage research into PSP and CBD.
CurePSP is the nonprofit organization for prime of life neurodegenerative diseases, a spectrum of fatal brain disorders that often strike during a person's most productive and rewarding years. Since it was founded in 1990, CurePSP has funded more than 180 research studies and is a leading source of support and advocacy for patients, families, and other caregivers and education and information for doctors and allied healthcare professionals. CurePSP is based in New York City. Please visit www.curepsp.org for more information.