# Biomarkers of disease severity and progression in Parkinson's

> **NIH VA IK2** · PORTLAND VA MEDICAL CENTER · 2024 · —

## Abstract

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder, and it is
even more prevalent in veterans, due to military-specific exposures that increase PD risk. There is great
phenotypic variability: some PD patients present primarily with tremor and retain good quality of life for
decades whereas others demonstrate a more malignant phenotype with more rapid progression to dementia
and severe motor impairments. The ability to predict which patients will exhibit slow or fast disease progression
would be invaluable for patient counseling and for clinical trial design. To date, no biomarkers have been
identified which predict PD progression. Given that mitochondrial dysfunction is an early and consistent cellular
hallmark of the disease that tracks with disease progression, measuring mitochondrial function could prove to
be one such predictive biomarker. Two promising approaches, magnetic resonance spectroscopic imaging
(MRSI) and measurement of Nrf2 activity in peripheral blood mononuclear cells (PBMCs), could close this
knowledge gap.
Significance: This work addresses two high-priority areas. It makes inroads into precision medicine through its
potential for predicting disease progression and laying foundation for improving clinical trial design and
expediting translation of promising preclinical work. It also focused on a neurocognitive disorder highly
prevalent within the VA population. The VA has an older average age, males are more likely to acquire the
disease, PD is recognized as a service-connected disease, and veterans with PD are more likely to rely solely
on the VA for their health care than veterans without PD.
Innovation: This proposal is innovative because we plan to be the first to apply ultrahigh field MRSI to
measure mitochondrial function in real time in the brains of patients with PD. Extending beyond static
measurements of phosphate-containing compounds, we will also be the first to apply magnetization transfer,
giving us further insight into mitochondrial dynamics and increasing the sensitivity of our assessments. Our
work will also assess whether imaging-based measures of mitochondrial dysfunction will be able to predict
subsequent clinical changes in PD progression. If so, this would provide the first biomarker that is able to
predict progression in individuals with PD.
Specific Aims: 1) Quantify mitochondrial bioenergetics in the PD brain by applying 31P-MRSI. 2) Evaluate
PBMC Nrf2 mRNA expression and its downstream effectors in PD patients compared to controls. 3)
Assess longitudinal changes in peripheral Nrf2 levels and 31P-MRSI-based changes in brain bioenergetics in
early PD patients, to determine whether differences in mitochondrial bioenergetics predict clinical disease
progression.
Methods: A cross-sectional study of early and mid-stage patients with PD and healthy controls will undergo
MRSI and peripheral blood analysis. One year later, the controls and early PD group will repeat these
...

## Key facts

- **NIH application ID:** 10788321
- **Project number:** 5IK2CX002539-02
- **Recipient organization:** PORTLAND VA MEDICAL CENTER
- **Principal Investigator:** Lee Neilson
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10788321

## Citation

> US National Institutes of Health, RePORTER application 10788321, Biomarkers of disease severity and progression in Parkinson's (5IK2CX002539-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10788321. Licensed CC0.

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