# BLR&D MERIT REVIEW RESEARCH CAREER SCIENTIST AWARD APPLICATION

> **NIH VA IK6** · VA SAN DIEGO HEALTHCARE SYSTEM · 2024 · —

## Abstract

Age-related neurodegenerative diseases such as Alzheimer’s disease (AD) and amyotrophic lateral sclerosis
(ALS) are the most common cause of morbidity in the Veteran population. Medical costs for U.S. Veterans of
Iraq and Afghanistan could be enormous because of differences between these wars and previous conflicts
due to today’s Veterans surviving injuries that would have been fatal in previous wars, and "polytraumatic"
injuries that require decades of costly physical and social rehabilitation. With no prevention or treatment,
individuals with neurodegenerative conditions could reach 11-16 million by 2050. In addition to age-related
neurodegeneration, depression among the elderly has been estimated to increase health care costs by 50%
and increase outpatient costs by 43 to 52% in these individuals compared to non-depressed patients. With this
growing Veteran population is an increase in chronic health conditions, and social and financial burdens on
their families and the health care system. Neurodegeneration diseases are closely associated with decreased
neuronal signaling, mitochondrial dysfunction, loss of synapses and neuromuscular junctions. Since receiving
the VA CDA in 2009, the Head laboratory has focused on targeting molecular mechanisms (via genetic and/or
pharmacologic interventions) to evoke functional neuronal and synaptic plasticity to improve cognitive and
motor function in the neurodegenerative brain and spinal cord respectively. As a result of continuous funding
from the VA (3 Merits since 2011) and NIH (NINDS R01 2011), in 2012 Dr. Head was bestowed the
Presidential Early Career Awards for Scientists and Engineers (PECASE) through the Department of Veterans
Affairs, which is the highest honor given by the United States Government to early-stage scientist and
engineers. Specifically, the Head laboratory investigates how caveolin (Cav), a cholesterol binding and
scaffolding protein within membrane/lipid rafts (MLRs), regulates synaptic signaling, mitochondrial function,
and neuroplasticity in neuronal models in vitro using human neurons derived from iPSCs and in animal models
of neurodegeneration such as AD and ALS. Cav-1 is a cholesterol-binding and membrane protein that is
essential for MLR formation and MLR-localization of neurotrophin receptors and synaptic proteins necessary
for synaptic function and neuroplasticity. Dr. Head engineered a genetic construct that contains a neuron-
targeted promoter (synapsin) to drive the expression of Cav-1 (termed SynCav1) specifically in neurons to
evoke neuroprotection and functional plasticity in the setting of disease or following traumatic injury (work
funded by NINDS, VA, and DoD). Dr. Head patented this novel gene therapy through the U.S. Patent Office in
March 2015 (U.S. Patent No. 8,969,077 B2: Neuronal specific targeting of caveolin expression to restore
synaptic signaling and improve cognitive function in the neurodegenerative brain and motor function in spinal
cord) of which the ...

## Key facts

- **NIH application ID:** 10813048
- **Project number:** 5IK6BX006318-02
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** BRIAN P HEAD
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10813048

## Citation

> US National Institutes of Health, RePORTER application 10813048, BLR&D MERIT REVIEW RESEARCH CAREER SCIENTIST AWARD APPLICATION (5IK6BX006318-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10813048. Licensed CC0.

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