Jupiter Orphan Therapeutics Announces First Patient Dosed in Phase I Dose Escalation Study of JOTROL™

JUPITER, Fla., Jan. 11, 2021 /PRNewswire/ -- Jupiter Orphan Therapeutics, Inc. ("JOT") a biotechnology company pioneering a novel and disease modifying product named JOTROL™, today announced that the first patient has been dosed in a Phase I dose escalation study of JOTROL™. The Phase I is conducted with healthy volunteers in various ages and include a food effect arm. Per protocol, the first patient cohort has been dosed and the study is continuing in January and February of 2021. Top line data is expected to be available in March 2021. The initial dose appear well-tolerated as the escalation continues toward clinically relevant doses. JOTROL™ is, through its unique bioavailability, the first and only resveratrol product that can deliver a therapeutically effective dose without causing any severe gastro-intestinal side effects. JOTROL™ is a platform product that is expected to be an effective treatment in many rare diseases such as ataxias, lysosomal storage disorders and mitochondrial diseases. 

 We are assuming positive Phase I results, which will be a Proof Of Concept of our product and have started preparations for Phase II trials in MPS-1, Friedreich's ataxia and MELAS in addition to MCI study preparation. We have presently cash covering us through 2021 and are targeting additional financing through an equity raise, possible partnering as well as utilizing non-dilutive funding sources to be able to start several Phase II trials later in 2021," stated Christer Rosén, Chairman and CEO.

Cytoprotective activities of kinetin purine isosteres

Barbara Maková, Václav Mik, Barbora Lišková, Gabriel González, Dominik Vítek, Martina Medvedíková, Beata Monfort, Veronika Ručilová, Alena Kadlecová, Prashant Khirsariya, Zoila Gándara Barreiro, Libor Havlíček, Marek Zatloukal, Miroslav Soural, Kamil Paruch, Benoit D'Autréaux, Marián Hajdúch, Miroslav Strnad, Jiří Voller, Bioorganic & Medicinal Chemistry, 2021, 115993, doi:10.1016/j.bmc.2021.115993. 

 Our findings indicate that kinetin isosteres protect Friedreich́s ataxia patient-derived fibroblasts against glutathione depletion, protect neuron-like SH-SY5Y cells from glutamate-induced oxidative damage, and correct aberrant splicing of the ELP1 gene in fibroblasts derived from a familial dysautonomia patient. Although the mechanism of action of kinetin derivatives remains unclear, our data suggest that the cytoprotective activity of some purine isosteres is mediated by their ability to reduce oxidative stress. Further, the studies of permeation across artificial membrane and model gut and blood-brain barriers indicate that the compounds are orally available and can reach central nervous system. Overall, our data demonstrate that isosteric replacement of the kinetin purine scaffold is a fruitful strategy for improving known biological activities of kinetin and discovering novel therapeutic opportunities.

DNA REPAIR PATHWAYS ARE ALTERED IN NEURAL CELL MODELS OF FRATAXIN DEFICIENCY

Jara Moreno-Lorite, Sara Pérez-Luz, Yurika Katsu-Jiménez, Daniel Oberdoerfer, Javier Díaz-Nido, Molecular and Cellular Neuroscience, 2021, 103587, doi:10.1016/j.mcn.2020.103587. 

 These results suggest that the deficiency of FXN leads to a down-regulation of DNA repair pathways that synergizes with oxidative stress to provoke DNA damage, which may be involved in the pathogenesis of FRDA. Thus, a failure in DNA repair may be considered a shared common molecular mechanism contributing to neurodegeneration in a number of hereditary ataxias including FRDA.