This week, CurePSP is announcing its semiannual crop of research grants. (Disclosure: I chair CurePSP’s Scientific Advisory Board, which reviews the grant applications and makes funding recommendations to the Board of Directors, of which I’m also a member.) Many granting agencies tend to favor senior researchers on the grounds that they’re known entities with a track record of success. CurePSP, however, has long tended to favor early-career applicants on grounds that they may bring new thinking and energy to the field and that our grant might make the difference in a young research’s choice of diseases to study for decades to come.

There were 22 applications in the current group. We chose to fund 3 early-career applicants – Drs. Bailey, Silva and Olah, all of whom happened to be women, and one world-class, senior guy, Dr. Geschwind. I’ll let the press release speak for itself.

CurePSP funds four new grants to study treatment of prime of life neurodegeneration

Studies at leading institutions may result in therapeutic approaches for PSP, CBD, FTD, and related diseases.

NEW YORK, NY (September 8, 2021) – CurePSP has awarded Venture Grants totaling $320,000 to scientists at Harvard Medical School, Columbia University, UT Southwestern Medical Center, and UCLA. The studies will investigate gene therapy, neuroprotective enzymes, activation of autophagy, and identification of microglia associated with toxic protein accumulation as possible therapeutic agents in the treatment of several neurodegenerative diseases.

Diseases like progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal dementia (FTD) are caused by the toxic accumulation of a naturally resident protein in the brain called tau that leads to destruction of neurons. Symptoms include loss of motor control, behavioral disinhibition, cognitive impairment, and difficulties in swallowing and speech. They are termed “prime of life” neurodegeneration because, unlike commonly occurring Alzheimer’s disease, they frequently strike in middle age. They are currently incurable and largely untreatable.

Dr. Rachel Bailey of the Center for Alzheimer’s and Neurodegenerative Diseases at UT Southwestern Medical Center in Dallas will study gene replacement therapy to combat toxic accumulation of the tau protein. Dr. Bailey will test a way to use a virus to deliver two types of RNA, one to prevent the manufacture of abnormal tau and the other to encode an aggregation-resistant form of tau.

Dr. Daniel H. Geschwind of UCLA’s Department of Neurology and his team will test four new, orally available drugs in mice genetically engineered to produce abnormal tau protein.  The drugs enhance the activity of an enzyme called puromycin-sensitive aminopeptidase, which both cuts up tau protein and enhances the brain cells’ “autophagy” system, which disposes of some types of abnormal proteins, including tau. 

Dr. Maria Catarina Lima da Silva of the Department of Neurology of Massachusetts General Hospital and Harvard Medical School in Boston will, like Dr. Geschwind, investigate small-molecule activators of autophagy to clear toxic protein accumulation in the brain. However, rather than using mice, Dr. Lima da Silva’s approach will utilize neurons grown from stem cells derived from skin biopsies of human patients.  She will study orally-available compounds that activate an enzyme called ULK1, an autophagy enhancer.

Dr. Marta Olah of Columbia University’s department of neurology in New York City will study microglia, the resident immune cells of the brain, which is recent years have been shown to be a major participant in the neurodegenerative process.  Dr. Olah will use a new method to sequence the RNA in individual microglial cells, creating a map of which cells are encoding which proteins in proximity to degenerating neurons.  This could generate new insights into the disease process and new targets for drugs.

CurePSP’s Venture Grants are awarded twice a year. Applications are reviewed and recommended to CurePSP’s board of directors by an independent scientific advisory board. The next application deadline is December 17, 2021.