AN INTERMEDIATE-SIZE EXPANDED ACCESS PROTOCOL FOR AMYOTROPHIC LATERAL SCLEROSIS WITH PRIDOPIDINE - THE SIGMA 1 RECEPTOR (S1R) HAS EMERGED AS AN ATTRACTIVE THERAPEUTIC TARGET IN ALS. MUTATIONS IN THE S1R ARE CAUSATIVE OF ALS AND THE DEGREE OF LOSS OF FUNCTION IN S1R PROTEIN DETERMINES AGE OF ONSET. S1R KNOCK-DOWN EXACERBATES PHENOTYPES IN ALS MOUSE MODELS, AND S1R ACTIVATION IMPACTS PATHWAYS THAT ARE KNOWN TO BE IMPLICATED IN ALS, I.E., NUCLEOCYTOPLASMIC TRANSPORT, PROTEIN QUALITY CONTROL, ENDOPLASMIC RETICULUM (ER) STRESS, MITOCHONDRIAL FUNCTION, AND AUTOPHAGY. RILUZOLE, EDARAVONE, AND PB-TURSO, THE CURRENT STANDARD-OF-CARE MEDICATIONS FOR ALS IN THE US, OFFER ONLY MODEST CLINICAL BENEFIT AND ARE NOT KNOWN TO ACT THROUGH THE S1R. NUEDEXTA, A NON-SELECTIVE S1R AGONIST, IS APPROVED FOR THE TREATMENT OF PSEUDOBULBAR AFFECT AND HAS BEEN SHOWN TO IMPROVE BULBAR FUNCTION IN A SUBSET OF PEOPLE LIVING WITH ALS. PRIDOPIDINE (PRILENIA THERAPEUTICS) IS A POTENT AND HIGHLY SELECTIVE SMALL MOLECULE

Summary

AN INTERMEDIATE-SIZE EXPANDED ACCESS PROTOCOL FOR AMYOTROPHIC LATERAL SCLEROSIS WITH PRIDOPIDINE - THE SIGMA 1 RECEPTOR (S1R) HAS EMERGED AS AN ATTRACTIVE THERAPEUTIC TARGET IN ALS. MUTATIONS IN THE S1R ARE CAUSATIVE OF ALS AND THE DEGREE OF LOSS OF FUNCTION IN S1R PROTEIN DETERMINES AGE OF ONSET. S1R KNOCK-DOWN EXACERBATES PHENOTYPES IN ALS MOUSE MODELS, AND S1R ACTIVATION IMPACTS PATHWAYS THAT ARE KNOWN TO BE IMPLICATED IN ALS, I.E., NUCLEOCYTOPLASMIC TRANSPORT, PROTEIN QUALITY CONTROL, ENDOPLASMIC RETICULUM (ER) STRESS, MITOCHONDRIAL FUNCTION, AND AUTOPHAGY. RILUZOLE, EDARAVONE, AND PB-TURSO, THE CURRENT STANDARD-OF-CARE MEDICATIONS FOR ALS IN THE US, OFFER ONLY MODEST CLINICAL BENEFIT AND ARE NOT KNOWN TO ACT THROUGH THE S1R. NUEDEXTA, A NON-SELECTIVE S1R AGONIST, IS APPROVED FOR THE TREATMENT OF PSEUDOBULBAR AFFECT AND HAS BEEN SHOWN TO IMPROVE BULBAR FUNCTION IN A SUBSET OF PEOPLE LIVING WITH ALS. PRIDOPIDINE (PRILENIA THERAPEUTICS) IS A POTENT AND HIGHLY SELECTIVE SMALL MOLECULE