# RR&D Research Career Scientist Award Application

> **NIH VA IK6** · JOHN D DINGELL VA MEDICAL CENTER · 2020 · —

## Abstract

Project Summary / Abstract
 The current VA-funded research activities of the nominee fall into two major categories: studies of the
chronic effects of TBI and studies of the non-motor symptoms of Parkinson's disease. With regard to TBI,
current studies in the nominee's lab are focusing on the most prevalent form of TBI seen in military personnel,
Veterans and civilians- repetitive, mild TBI (rmTBI). This insidious form of head injury has many comorbid
psychiatric, cognitive, sleep and behavioral abnormalities associated with it yet it remains poorly understood
and effective treatments for it are not available. The lab of the nominee recently developed a new animal
model of rmTBI that has opened new avenues of investigation into the chronic outcomes of head injury. Initial
work has established that the model can be used to deliver numerous impacts to the head of a mouse without
causing skull fracture, intracranial bleeding or paralysis. However, this model is unique in that it results in many
of the long-term outcomes that are being seen in Veterans and athletes to include depression- and anxiety-like
affective disorders, sleep disturbances, cognitive decline and a CTE-like neuropathology. Another unique
element this line of research is the testing of a new therapy for rmTBI. To date, all clinical tests of TBI therapies
have failed and the possibility must be considered that the reason for this 100% failure rate is related to the
use of animal models of TBI that do not faithfully create impact conditions to which humans are exposed. Our
new model of rmTBI fills this gap. Soon after publication of our new model, we were approached by Acetylon
Pharmaceuticals to test their new HDAC6 inhibitor as a therapy for rmTBI. Studies underway with this new
compound are producing promising results and emerging tests will also determine its effectiveness in relieving
the comorbid conditions that often accompany rmTBI.
 With regard to Parkinson's disease (PD), it is becoming that the non-motor symptoms (NMS) of this
neurodegenerative disease lower the quality of life for Veterans more so than the much better understood
motor symptoms. The NMS of Parkinson's can include many of the same conditions cited above for rmTBI. To
date, the vast majority of preclinical and clinical studies of PD have focused on the dopamine (DA) neuronal
system and how its destruction can result in disease symptomology. Most therapies for PD also target the DA
system. As is the case for rmTBI, there is no effective therapy for the NMS of PD. However, while vastly
underappreciated, the serotonin (5HT) and norepinephrine (NE) systems are also extensively altered in PD.
The lab of the nominee has created two genetically modified mouse strains that lack brain 5HT. One is a
constitutive null mutation in the gene for tryptophan hydroxylase and a new strain is a tamoxifen-inducible
knockout of the same gene. The key facet that makes these mouse strains so applicable to the study of the
NMS of P...

## Key facts

- **NIH application ID:** 9989673
- **Project number:** 5IK6RX002419-04
- **Recipient organization:** JOHN D DINGELL VA MEDICAL CENTER
- **Principal Investigator:** Donald M Kuhn
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989673

## Citation

> US National Institutes of Health, RePORTER application 9989673, RR&D Research Career Scientist Award Application (5IK6RX002419-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9989673. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*