# Novel Protein Aggregation Inhibitors and Upper Motor Neuron Stabilizers for ALS and other Neurodegenerative Diseases

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $622,539

## Abstract

Abstract:
Recent developments in chemistry, genetics, and biology revealed that many of the age-related neurodegenerative
diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and ALS/FTD share protein
accumulation as the common cause of neuropathology. In addition, the number and kinds of compounds
generated within the last years have exponentially increased. However, these developments in science have not
yet successfully translated into effective drug discoveries for patients. This proposal is a collaborative project
between the Silverman and Ozdinler Labs, blending expertise in medicinal chemistry and selective neuronal
vulnerability, respectively. In an effort to expedite drug discovery and to identify novel compounds that can move
into clinical trials for ALS and age-related disorders, which develop in part because of protein aggregation, such
as Alzheimer's disease, we have developed a novel strategy and a strong team effort. This strategy also could,
more broadly, ameliorate other neurodegenerative diseases in which voluntary movement is affected and in
which protein aggregation is a major underlying cause. Dr. Silverman discovered several compounds that inhibit
protein aggregation in cells and that have favorable pharmacokinetic properties, and Dr. Ozdinler developed a
novel in vitro and in vivo preclinical drug screening/verification platform using the improved health of upper motor
neurons (UMNs) that become diseased from different underlying factors, as the read-out. Recent discoveries
from the Ozdinler group reveal the importance of improving UMN health early in the disease and that maintaining
UMN health is crucial for effective drug discovery efforts. It is unfortunate that this important neuron population
has never before been considered in preclinical studies, even for diseases that are identified by their selective
and progressive degeneration. This proposal will develop the first preclinical platform that utilizes diseased UMNs
for the assessment of novel compounds generated in the Silverman lab that inhibit protein aggregation and
improve the health of diseased UMNs both in vitro and in vivo. Upon completion of this proposal, we will move the
field forward along two different avenues by developing a new preclinical assay that incorporates UMN health as
the read-out, and by identifying novel drugs for age-related neurodegenerative diseases that develop from
problems with protein aggregation .

## Key facts

- **NIH application ID:** 10147625
- **Project number:** 5R01AG061708-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Pembe Hande Ozdinler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $622,539
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10147625

## Citation

> US National Institutes of Health, RePORTER application 10147625, Novel Protein Aggregation Inhibitors and Upper Motor Neuron Stabilizers for ALS and other Neurodegenerative Diseases (5R01AG061708-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10147625. Licensed CC0.

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