好色先生

好色先生

Explore the latest content from across our publications
Join The AAN

Log In

Forgot Password?
Create New Account

Loading... please wait

Abstract Details

Development of Integrated Stress Response Inhibitor RTX-117 as a Treatment for Neurodegenerative Diseases
Neuromuscular and Clinical Neurophysiology (EMG)
P9 - Poster Session 9 (11:45 AM-12:45 PM)
11-028
To evaluate the efficacy of RTX-117 in the treatment of neurodegenerative diseases.
The integrated stress response (ISR) is a conserved translational and transcriptional program that enables the cell to return to homeostasis in response to a variety of stressors in the cytoplasm and endoplasmic reticulum. Unresolved chronic ISR activation can lead to cellular apoptosis and is a hallmark of a number of neurodegenerative diseases including vanishing white matter (VWM), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD). RTX-117 is a small molecule inhibitor of the ISR which is orally bioavailable and highly brain penetrant, suggesting its utility in treating ISR-related pathologies.
We evaluated RTX-117 in several in vitro cellular models including induced pluripotent stem cell (iPSC)-derived motor neurons, and in vivo studies in VWM and ALS mouse models. A Phase 1 study in healthy volunteers will be initiated in early 2025.
RTX-117 is a potent inhibitor of the ISR pathway as measured by the suppression of an ISR-mediated gene signature in vitro and in vivo. In the VWM in vivo study, RTX-117 improved motor function and body weight gain in treated mice at the low dose of 0.1 mg/Kg. Data from other studies will also be presented.
RTX-117 is a promising therapeutic option for neurodegenerative diseases where chronic ISR is implicated.
Authors/Disclosures
Sridhar Narayan, PhD
PRESENTER 		Dr. Narayan has received personal compensation for serving as an employee of ReviR Therapeutics.
Mary McMahon, PhD Dr. McMahon has received personal compensation for serving as an employee of ReviR Therapeutics .
Steve Lianoglou, PhD Mr. Lianoglou has received personal compensation for serving as an employee of ReviR Therapeutics.
Jinxing Li, PhD Dr. Li has nothing to disclose.
Jiacheng Zhang, PhD Dr. Zhang has nothing to disclose.
Jawad Abid Mr. Abid has nothing to disclose.
Yang Liu (ReviR Therapeutics) No disclosure on file
Paul R. August, PhD Dr. August has received personal compensation for serving as an employee of ReviR Therapeutics. Dr. August has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Charcot Marie Tooth Research Foundation. Dr. August has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for AcuraStem. Dr. August has stock in Acurastem. Dr. August has stock in ReviR Therapeutics. The institution of Dr. August has received research support from CMTRF.