Progressing PrC-210 to Clinical Treatment for the Prevention of Neurodegenerative Diseases After Radiation
Abstract
This proposal is designed to explore and better understand the basic mechanisms and relationship between acute radiation exposure and the development of long-term neurodegeneration. We will progress the development of a novel biomarker for measurement of the severity of brain radiation exposure and subsequent brain dysfunction. We will also pursue further development of the innovative PrC-210 free radical scavenger as an innovative treatment for the prophylaxis and mitigation of brain radiation damage and prevention of neurodegenerative disease development after radiation exposure. Rationale and Scientific Objective: It is well established that exposure to radiation can lead to profound functional and morphological changes in brain tissues, cognitive decline, and the development of dementia, such as Parkinson’s disease and Alzheimer’s dementia. The toxic brain effects of radiation are especially pronounced and rapid in children exposed to high-energy, anti-cancer radiation therapy. In adults, this correlation is less obvious, as the cognitive decline is slower, nonetheless, it has been established in epidemiological studies of Baltic and Ukrainian workers after the nuclear accident at Chernobyl. The underlying mechanism of radiation-associated brain neurodegeneration is still not well understood. In this proposal we will: (i) present first evidence for a central mechanism that plausibly connects irradiation with the development neurodegeneration, (ii) propose experiments for further exploration of the mechanism, and (iii) propose the simultaneous development of a credible therapeutic and diagnostic intervention that could allow prevention of the development of neurodegeneration and suppression of its progression. Military Benefits: Prevention or significant suppression of both acute radiation-induced brain dysfunction and emergent long-term neurodegenerative disease in military and civilian populations would impact real-time care of radiation-exposed military staff as well as greatly reduce the cost of long-term care. Acute treatment of radiation exposure, from battlefield settings to clinical radiation oncology settings, with PrC-210 would protect the brain and thereby reduce brain damage severity. PrC-210 can be stored at room temperature, can be administered in a ready-to-use oral capsule or intravenous format, and therefore could be used flexibly when needed in a variety of clinical and real-world settings. The studies proposed here can quantitatively measure the effect that PrC-210 confers on radiation-induced brain function loss, and in forward-looking studies, we will also determine PrC-210 efficacy in suppressing brain function loss in mouse ALS and Alzheimer’s models, particularly when accelerated by brain irradiation. If proven to be effective here in preventing or significantly slowing the onset and the development of neurodegeneration in excellent mouse models, PrC-210 could then be used for the prevention and treatment of neurodegeneration in humans in a variety of radiation toxicity and disease settings.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310832
Entities
People
- William Fahl
Organizations
- United States Army