# Mitigation of Radiation Therapy Induced Neuroinflammation and Cognitive Dysfunction

> **NIH NIH R44** · IMMUNOCHEM THERAPEUTICS, LLC · 2021 · $777,049

## Abstract

PROJECT SUMMARY
Cognitive decline and deterioration of long-term cognitive performance are major side effects of CNS cancer
treatment. Brain metastases are the most common CNS malignancies and a common cause of morbidity and
mortality in about 40% of all cancer patients with systemic disease, affecting over 170,000 patients in the US
annually. As most systemic chemotherapy agents do not cross the blood brain barrier, the main treatment
modalities for brain metastases include surgery, whole brain radiation therapy (WBRT)) and/or stereotactic
radiosurgery. The multidisciplinary management of brain metastases aims to achieve durable tumor control
within the brain without compromising neurocognitive functioning. However, current results are disappointing.
Despite the advantages of WBRT for disease control, cognitive impairment can be seen as early as 3 to 4
months after WBRT, and affects approximately 80-90% of patients, with memory and executive function being
the major cognitive domains affected.
Abnormal levels of proinflammatory cytokines (PIC) induced in response to ionizing radiation have been
proposed as a potential mechanism underlying WBRT-induced cognitive impairment. Shortly after radiation
treatment of a tissue, a cascade of cytokines and chemokines is initiated and these mediators perpetuate and
augment the inflammatory response for long periods of time, leading to chronic inflammation and tissue injury.
MW151 is an orally active, small molecule drug candidate that restores injury- or disease-induced
dysregulation of PIC production towards homeostasis without immunosuppression. MW151 selectively
attenuates the PIC cascade that occurs in a diverse array of animal models, including mitigation of CNS and
skin radiation injury even when given days after radiation exposure. Our goal in the proposed clinical feasibility
study is to test the hypothesis that plasma PIC levels are stabilized in patients receiving MW151 in the course
of WBRT for the treatment of brain metastases and that MW151 treatment can attenuate therapy-induced
cognitive dysfunction in these patients.
Our specific aims are: Aim 1 – Preparation for clinical study. Aim 2 – Recruitment and conduct of the clinical
study. Aim 3: Evaluation of clinical study outcomes. This pilot study will provide data regarding the feasibility of
the clinical use of MW151 as an adjunct to WBRT, the current standard of care, to reduce the cognitive decline
after radiation therapy for patients with brain metastases.

## Key facts

- **NIH application ID:** 10414174
- **Project number:** 4R44CA236382-02
- **Recipient organization:** IMMUNOCHEM THERAPEUTICS, LLC
- **Principal Investigator:** Vinai Gondi
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $777,049
- **Award type:** 4N
- **Project period:** 2019-05-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10414174

## Citation

> US National Institutes of Health, RePORTER application 10414174, Mitigation of Radiation Therapy Induced Neuroinflammation and Cognitive Dysfunction (4R44CA236382-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10414174. Licensed CC0.

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