RASRx1902 / RASRx - LARVOL DELTA

Activation of the protective arm of renin-angiotensin system enhances mitochondrial turnover improving respiration and decreasing integrated stress response in a human Complex III deficiency model. (PubMed, bioRxiv) - "Remarkably, CAP-1902 was ultimately able to restore key defects in CIII-deficient fibroblasts by rescuing bioenergetics and correcting both the aberrant lysosomal distribution and the elevated integrated stress response markers, which is consistent with a shift toward a healthier mitochondrial population. In summary, we describe the first potential GPCR-mediated treatment of mitochondrial diseases and demonstrate that MasR activation by CAP-1902 induces mitochondrial turnover and improves mitochondrial function."

Journal • Metabolic Disorders

CAP-1902 Enhances Muscle Function in mdx Mice (MDA 2024) - "Circulating inflammatory biomarkers were significantly decreased and anti-inflammatory markers were increased following treatment with CAP-1902. Activation of mitophagy may serve as a novel therapeutic option for DMD patients to improve muscle function."

Preclinical • Duchenne Muscular Dystrophy • Fibrosis • Genetic Disorders • Immunology • Metabolic Disorders • Muscular Dystrophy

Mechanisms of neuro- and cardioprotection of MAS agonists in the TAC model. (PubMed, Alzheimers Dement) - "The Mas agonist RASRx1902 significantly decreased several measures of AD-like pathology in the TAC model with particular focus on cardioprotection and mitochondrial function, indicating that it may be beneficial in those with hypertension as a risk factor for AD development. Future work will focus on further characterizing RASRx1902 effects in affected cellular pathway changes, efficacy in a pilot study examining cerebral blood flow, blood brain barrier integrity, and effects on neuronal function."

Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Congestive Heart Failure • Fibrosis • Heart Failure • Hypertension • Immunology • Metabolic Disorders

[VIRTUAL] Pharmacodynamic Assessment of Orally Available Mas Agonists (AAIC 2021) - "Microglial mitochondrial superoxide is the main contributor to promote OS, a contributor to AD neurodegeneration. Our data clearly show that our metabolically stable small molecule Mas agonists have the capacity to decrease ROS levels in microglia and might mediate neuronal survival through Akt/Erk signaling pathway. Therefore, RASRx1902 and RASRx1911 are promising novel drug for the treatment of AD."

PK/PD data • Alzheimer's Disease • CNS Disorders • Solid Tumor

[VIRTUAL] Mechanisms of Neuro- and Cardioprotection of MAS Agonists in TAC Model (AAIC 2021) - "The Mas agonist RASRx1902 significantly decreased several measures of AD-like pathology in the TAC model with particular focus on cardioprotection and mitochondrial function, indicating that it may be beneficial in those with hypertension as a risk factor for AD development. Future work will focus on further characterizing RASRx1902 effects in affected cellular pathway changes, efficacy in a pilot study examining cerebral blood flow, blood brain barrier integrity, and effects on neuronal function."

Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Congestive Heart Failure • Fibrosis • Heart Failure • Hypertension • Immunology • Metabolic Disorders

[VIRTUAL] Mitigation of Cognitive Decline and Brain Pathology after Transaortic Constriction by Mas Agonists (AAIC 2021) - "In conclusion, RASRx1902 and RASRx1911 resulted in improved cognition and reduced OS and inflammation in the brain of mice that had undergone TAC surgery."

Immunology • Inflammation • Metabolic Disorders

Pharmacodynamic Assessment of Orally Available Mas Agonists (AAIC 2021) - "Microglial mitochondrial superoxide is the main contributor to promote OS, a contributor to AD neurodegeneration. Our data clearly show that our metabolically stable small molecule Mas agonists have the capacity to decrease ROS levels in microglia and might mediate neuronal survival through Akt/Erk signaling pathway. Therefore, RASRx1902 and RASRx1911 are promising novel drug for the treatment of AD."

PK/PD data • Alzheimer's Disease • CNS Disorders • Solid Tumor

Mitigation of Cognitive Decline and Brain Pathology after Transaortic Constriction by Mas Agonists (AAIC 2021) - "In conclusion, RASRx1902 and RASRx1911 resulted in improved cognition and reduced OS and inflammation in the brain of mice that had undergone TAC surgery."

Immunology • Inflammation • Metabolic Disorders