# Functional Biomarkers for ALS

> **NIH NIH R21** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2022 · $253,794

## Abstract

Project Summary
 Functional non-invasive biomarkers are critical for therapeutic target engagement outcomes in
progressive rare diseases. Amyotrophic lateral sclerosis (ALS) clinical trial development has an urgent need for
functional biomarkers to assess therapeutic response and target engagement. We will fulfill that urgent need.
 We have a history using functional blood-based biomarkers for clinical trials in ALS. Rasagaline (a
neuroprotective compound) showed mitochondrial biomarker target -engagement in an open-labeled trial. A
subsequent multi-center placebo-controlled trial failed to replicate target engagement. Disparities among
clinical trial outcomes revealed issues with sample handling and the need for a generalized estimating
equation (GEE) statistical model. Without the ability to accurately detect target engagement therapeutic
opportunities will be lost.
 ALS pathological features include mitochondrial dysfunction and loss of proteostasis (protein
aggregation). Mitochondrial dysfunction and proteostasis are intricately linked biological modalities which are
key targets for upcoming clinical trials in ALS. These clinical trials will benefit from our functional biomarkers.
We will clinically validate blood based mitochondrial and proteostasis biomarker protocols for use as indices of
target engagement in future clinical trials. We will compare mitochondrial and proteostasis biomarkers within
ALS and control subjects over eight months. We will develop a GEE statistical model to provide guidance for
power calculations in our future planned clinical trials. We will determine biomarker relationships and develop a
predictive statistical approach for our novel functional biomarkers.

## Key facts

- **NIH application ID:** 10423605
- **Project number:** 1R21TR003589-01A1
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Heather M. Wilkins
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $253,794
- **Award type:** 1
- **Project period:** 2022-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10423605

## Citation

> US National Institutes of Health, RePORTER application 10423605, Functional Biomarkers for ALS (1R21TR003589-01A1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10423605. Licensed CC0.

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