# Mechanisms of Disease and Treatments in Novel Metabolic Development Brain Disorders

> **NIH NIH R01** · BROWN UNIVERSITY · 2022 · $28,043

## Abstract

PROJECT SUMMARY
We have recently identified a novel human neurogenetic disorder caused by loss-of-function mutations in the
mitochondrial enzyme glutamate pyruvate transaminase 2 (GPT2). Genetic metabolic diseases, such as GPT2
disease, offer a powerful lens to investigate mechanisms of metabolism in human brain. Also, metabolic
diseases may be amenable to treatments via dietary restrictions or supplements. GPT2 disease involves
postnatal undergrowth of brain and progressive spastic paraplegia. Based on our extensive preliminary data, we
have established potential treatment strategies for GPT2 disease. To guide these interventions in children, we
are currently completing needed pre-clinical studies under the awarded parent grant “Mechanisms of disease
and treatment in novel metabolic developmental brain disorders 1R01NS121618-01A1”. This application
represents a request for supplemental funding to support the post-baccalaureate training of Mr. Kenneth Bradley.
Mr. Bradley is a recent Brown University graduate and will be a research assistant working on projects under the
scope of the parent grant within the Morrow Laboratory. Mr. Bradley will work primarily on training and
conducting studies related to Aim 1 of this project, since Mr. Bradley is specifically interested in neurogenetics
and motor behavior in neurodevelopmental and neurodegenerative conditions. Aim 1 is focused on in vivo
studies of Gpt2-mediated growth of motor neurons. Our Gpt2-null mouse recapitulates key aspects of disease,
such as hindlimb motor abnormalities, akin to spastic paraplegia seen in patients. This supplement outlines
research and training plans that will build-upon Mr. Bradley’s existing skillset, and that will dovetail with his
scientific interests going forward. In addition to learning mammalian genetics, neurodevelopment and the
laboratory techniques of histology, microscopy and behavior assays, Mr. Bradley will be provided with a
mentorship on career development from multiple mentors and supervisors, will attend a conference, and receive
training in data analysis and manuscript preparation. Taken together, these experiences will assist Mr. Bradley
as he prepares for the next phase of his career in the biomedical workforce.
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## Key facts

- **NIH application ID:** 10622084
- **Project number:** 3R01NS121618-01A1S1
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Eric M Morrow
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $28,043
- **Award type:** 3
- **Project period:** 2022-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10622084

## Citation

> US National Institutes of Health, RePORTER application 10622084, Mechanisms of Disease and Treatments in Novel Metabolic Development Brain Disorders (3R01NS121618-01A1S1). Retrieved via AI Analytics 2026-06-15 from https://api.ai-analytics.org/grant/nih/10622084. Licensed CC0.

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