Omigapil (SNT-317) / Santhera - LARVOL DELTA

Stress-induced nuclear GAPDH: Scientific update and clinical application. (PubMed, Neurotherapeutics) - "Nevertheless, the clinical trials for Parkinson's disease and amyotrophic lateral sclerosis with one of these compounds Omigapil were unsuccessful. Including these failure cases, this review article discussed the scientific frontline of GAPDH, particularly stress-induced nuclear GAPDH, and its potential for clinical applications."

Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • GAPDH

Phase 1 Open-Label Study of Omigapil in Patients With LAMA2- or COL6-Related Dystrophy. (PubMed, Neurol Genet) - P1 | "This study provides Class IV evidence of omigapil in a dose-finding phase 1 study. Clinical Trials NCT01805024."

Journal • P1 data • CNS Disorders • Muscular Dystrophy • Pediatrics • Rare Diseases • COL6A1 • GAPDH • LAMA2

Single-neuron neurodegeneration as a degenerative model for Parkinson's disease. (PubMed, Neural Regen Res) - "Successful preclinical studies with coenzyme Q10, mitoquinone, isradipine, nilotinib, TCH346, neurturin, zonisamide, deferiprone, prasinezumab, and cinpanemab prompted clinical trials. In conclusion, based on the hypothesis that the neurodegenerative process of idiopathic Parkinson's disease corresponds to a single-neuron neurodegeneration model, we must search for molecules that increase the expression of the neuroprotective enzymes DT-diaphorase and glutathione transferase M2-2. It has been observed that the activation of the Kelch-like ECH-associated protein 1/nuclear factor (erythroid-derived 2)-like 2 pathway is associated with the transcriptional activation of the DT-diaphorase and glutathione transferase genes."

Journal • Review • CNS Disorders • Movement Disorders • Parkinson's Disease • KEAP1

Reducing acetylated tau is neuroprotective in brain injury. (PubMed, Cell) - "Ac-tau is thus a therapeutic target and potential blood biomarker of TBI that may represent pathologic convergence between TBI and AD. Increased ac-tau in human AD brain is further augmented in AD patients with history of TBI, and patients receiving the p300/CBP inhibitors salsalate or diflunisal exhibit decreased incidence of AD and clinically diagnosed TBI."

Journal • Alzheimer's Disease • CNS Disorders • Muscular Dystrophy • Vascular Neurology • GAPDH • SIRT1

LAMA2-Related Dystrophies: Clinical Phenotypes, Disease Biomarkers, and Clinical Trial Readiness. (PubMed, Front Mol Neurosci) - "The first clinical trial for the LAMA2-RDs was a phase 1 pharmacokinetic and safety study of the anti-apoptotic compound omigapil, based on preclinical studies performed in the dy/dy and dy/dy mouse models...Natural history studies, including a five-year prospective natural history and comparative outcome measures study in patients with LAMA2-RD, have helped to better delineate the natural history and identify viable outcome measures. Plans for further clinical trials for LAMA2-RDs are presently in progress, highlighting the necessity of identifying adequate, disease-relevant biomarkers, capable of reflecting potential therapeutic changes, in addition to refining the clinical outcome measures and time-to-event trajectory analysis of affected patients."

Biomarker • Clinical • Journal • Review • Muscular Atrophy • Muscular Dystrophy

Pharmacokinetic Study With Assessment of Safety and Tolerability of Omigapil in Children and Adolescents With Congenital Muscular Dystrophy (clinicaltrials.gov) - P1; N=24; Not yet recruiting; Sponsor: Santhera Pharmaceuticals; Initiation date: May 2014 ->Dec 2014 ; Trial primary completion date: Dec 2014 ->Sep 2016

Trial initiation date • Trial primary completion date • Biosimilar

Host proteins identified in extracellular viral particles as targets for broad-spectrum antiviral inhibitors. (PubMed, J Proteome Res) - "Compounds that target proteins incorporated into virions with high frequency, but with no known antiviral activity, were assayed in a scalable viral screening platform and hits were tested in competent viral systems. One of these molecules, GAPDH modulating small molecule CGP 3466B maleate (Omigapil), exhibited a dose-dependent inhibition of HIV, dengue virus, and Zika virus."

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Nitrosylation of GAPDH augments pathological tau acetylation upon exposure to amyloid-β. (PubMed, Sci Signal) - "The abundance of GAPDH-SNO was increased in postmortem brain samples from AD patients. Preventing the increase in GAPDH-SNO abundance in both cultured neurons and mice, either by overexpression of the nitrosylation mutant of GAPDH (GAPDH C150S) or by treatment with the GAPDH nitrosylation inhibitor CGP3466B (also known as omigapil), abrogated Aβ-induced tau acetylation, memory impairment, and locomotor dysfunction in mice, suggesting that this drug might be repurposed to treat patients with AD."

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