NRG Therapeutics awarded grant funding from target ALS to support the development of mPTP inhibitors as novel treatments for ALS/MND
Stevenage, UK, 5 August 2024 - NRG Therapeutics, Ltd., an innovative neuroscience company targeting mitochondrial dysfunction, is pleased to announce that it has been awarded a non-dilutive grant from Target ALS Foundation.
It is one of five recipients of the 2024 In Vivo Target Validation grants in collaboration with Biospective. The funding will be used to support its discovery programme for a treatment for Amyotrophic Lateral Sclerosis (ALS) (also known as Lou Gehrig’s disease or Motor Nuerone Disease).
NRG Therapeutics is applying breakthrough science in the field of mitochondrial biology to develop first-in-class treatments for neurodegenerative diseases including ALS/MND. It has discovered a new class of small molecule mitochondrial permeability transition pore (mPTP) inhibitors that can block mitochondrial dysfunction. Its inhibitors are designed to penetrate the brain effectively when taken orally.
Target ALS is committed to breaking down scientific research barriers to develop effective biomarkers and treatments for ALS. The In Vivo Target Validation Program aims to generate high-quality data on candidate therapeutics in animal models of ALS, provide access to in-kind funding for a resource-intensive step of drug discovery, and accelerate the progress of candidate therapeutics from preclinical testing towards clinical trials.
Mitochondria, the batteries of cells, are crucial for energy production, especially in brain cells which have high energy demands. In diseases like ALS, mitochondria become defective, leading to brain cell death and disease progression. Recent findings have shown that dysfunctional TDP43 protein – found in nearly all ALS patients – disrupts mitochondrial function and undesirably activates the immune system.
Announcing the awards, Target ALS said, “We are thrilled to announce the recipients of the Target ALS In Vivo Target Validation grants, focusing on proof-of-concept studies for promising therapeutics in a TDP-43 mouse model. This initiative, in collaboration with Biospective, is designed to accelerate the evaluation of potential therapeutics, bridging the gap from preclinical research to clinical trials.”
Biospective has implemented a modified, slower progressing version of the TDP-43 NLS8 (or DELTA-NLS) mouse model that was originally developed at the University of Pennsylvania (Walker et al., 2015). This model mimics disease symptoms and pathology that people living with ALS experience, including cytoplasmic TDP-43 mislocalization, neurodegeneration, and motor deficits. Using this standardized model, the team at Biospective will conduct robust behavioral and molecular assessments of candidate therapeutics for these preclinical efficacy studies. Successful results in this mouse model will enable groups to move their therapeutic candidate toward the clinic.
NRG Therapeutics’ co-founder and CEO Dr Neil Miller said, “Preliminary experiments using a mouse model of ALS which contains the human gene for TDP-43 showed that our mPTP inihibitor candidate therapeutic reduced brain cell death. However, due to the rapid disease progression in that mouse model, a full assessment of the therapeutic potential was not possible. This project aims to evaluate NRG’s small molecule inhibitor, in a modified ALS TDP-43 mouse model that progresses more slowly. This will allow for a comprehensive assessment of the molecule’s ability to protect mitochondria, reduce brain cell death, and decrease immune system activation. Additionally, the study will measure improvements in muscle function and strength. If successful, this project will provide crucial support for advancing our mPTP inhibitor into clinical trials for ALS.”
