Petrillo, S.; D’Amico, J.; La Rosa, P.; Bertini, E.S.; Piemonte, F. Int. J. Mol. Sci. 2019, 20, 5211. Doi:10.3390/ijms20205211 (registering DOI)
Different redox drugs, joined by their ability to modulate the NRF2 pathway, elicit differential response profiles in FRDA fibroblasts. Using drugs aimed at preventing inflammation (SFN, NAC), lipid peroxidation (DMF, OMAV, and EPI-743), or redox imbalance (SFN), “multi-target” synergic therapies can be developed in FRDA, based on the patient’s clinical conditions and therapeutic needs.
Tuesday, October 22, 2019
Sunday, October 20, 2019
Safety and Biodistribution of Human Bone Marrow-Derived Mesenchymal Stromal Cells Injected Intrathecally in Non-Obese Diabetic Severe Combined Immunodeficiency Mice: Preclinical Study
Mari Paz Quesada, David García-Bernal, Diego PastorAlicia Estirado, Miguel Blanquer, Ana Mª García-HernándezJosé, M. Moraleda, Salvador Martínez. Eng Regen Med (2019) 16: 525. doi:10.1007/s13770-019-00202-1
Mesenchymal stromal cells (MSCs) have potent immunomodulatory and neuroprotective properties, and have been tested in neurodegenerative diseases resulting in meaningful clinical improvements. Regulatory guidelines specify the need to perform preclinical studies prior any clinical trial, including biodistribution assays and tumourigenesis exclusion. We conducted a preclinical study of human bone marrow MSCs (hBM-MSCs) injected by intrathecal route in Non-Obese Diabetic Severe Combined Immunodeficiency mice, to explore cellular biodistribution and toxicity as a privileged administration method for cell therapy in Friedreich’s Ataxia.
Mesenchymal stromal cells (MSCs) have potent immunomodulatory and neuroprotective properties, and have been tested in neurodegenerative diseases resulting in meaningful clinical improvements. Regulatory guidelines specify the need to perform preclinical studies prior any clinical trial, including biodistribution assays and tumourigenesis exclusion. We conducted a preclinical study of human bone marrow MSCs (hBM-MSCs) injected by intrathecal route in Non-Obese Diabetic Severe Combined Immunodeficiency mice, to explore cellular biodistribution and toxicity as a privileged administration method for cell therapy in Friedreich’s Ataxia.
Friday, October 18, 2019
Protocol of a randomized, double-blind, placebo-controlled, parallel-group, multicentre study of the efficacy and safety of nicotinamide in patients with Friedreich ataxia (NICOFA)
Kathrin Reetz, Ralf-Dieter Hilgers, Susanne Isfort, Marc Dohmen, Claire Didszun, Kathrin Fedosov, Jennifer Kistermann, Caterina Mariotti, Alexandra Durr, Sylvia Boesch, Thomas Klopstock, Francisco Javier Rodríguez de Rivera Garrido, Ludger Schöls, Thomas Klockgether, Massimo Pandolfo, Rudolf Korinthenberg, Philip Lavin, Geert Molenberghs, Vincenzo Libri, Paola Giunti, Richard Festenstein, Jörg B. Schulz & the EFACTS or NICOFA study group. Neurological Research and Practice volume 1, Article number: 33 (2019) doi:10.1186/s42466-019-0038-9
Currently, no treatment that delays with the progression of Friedreich ataxia is available. In the majority of patients Friedreich ataxia is caused by homozygous pathological expansion of GAA repeats in the first intron of the FXN gene. Nicotinamide acts as a histone deacetylase inhibitor. Dose escalation studies have shown, that short term treatment with dosages of up to 4 g/day increase the expression of FXN mRNA and frataxin protein up to the levels of asymptomatic heterozygous gene carriers. The long-term effects and the effects on clinical endpoints, activities of daily living and quality of life are unknown.
Currently, no treatment that delays with the progression of Friedreich ataxia is available. In the majority of patients Friedreich ataxia is caused by homozygous pathological expansion of GAA repeats in the first intron of the FXN gene. Nicotinamide acts as a histone deacetylase inhibitor. Dose escalation studies have shown, that short term treatment with dosages of up to 4 g/day increase the expression of FXN mRNA and frataxin protein up to the levels of asymptomatic heterozygous gene carriers. The long-term effects and the effects on clinical endpoints, activities of daily living and quality of life are unknown.
Thursday, October 17, 2019
MINORYX THERAPEUTICS RECEIVES FDA ORPHAN DRUG DESIGNATION FOR LERIGLITAZONE IN FRIEDREICH’S ATAXIA
17 October, 2019.
Mataró, Barcelona, Spain and Charleroi, Belgium, October 17, 2019 – Minoryx Therapeutics, a company that specializes in the development of innovative treatments for orphan Central Nervous System (CNS) diseases, today announces that its lead drug candidate, leriglitazone (MIN-102), has been granted Orphan Drug Designation in Friedreich’s Ataxia by the US Food and Drug Administration (FDA).
Mataró, Barcelona, Spain and Charleroi, Belgium, October 17, 2019 – Minoryx Therapeutics, a company that specializes in the development of innovative treatments for orphan Central Nervous System (CNS) diseases, today announces that its lead drug candidate, leriglitazone (MIN-102), has been granted Orphan Drug Designation in Friedreich’s Ataxia by the US Food and Drug Administration (FDA).
Wednesday, October 16, 2019
Orphan Drugs In Development For The Treatment Of Friedreich’s Ataxia: Focus On Omaveloxolone
Shaila D Ghanekar, Wai Wai Miller, Colin J Meyer, Kevin J Fenelon, Alvin Lacdao, Theresa A Zesiewicz; Degenerative Neurological and Neuromuscular Disease 15 October 2019 Volume 2019:9 Pages 103—107 doi:10.2147/DNND.S180027
Investigations into the pathological mechanisms of FRDA have revealed the central role of frataxin deficiency and the subsequent lack of transcription factor Nrf2. Consequently, the Nrf2 activators discussed here as well as the several treatments in development focus on reversing the oxidative stress environment caused by frataxin deficiency. While the discussed orphan drugs show promise in the treatment of FRDA, further investigations must be conducted in order to ensure the efficacy and safety of such drugs, as well as to determine even more therapeutic options.
Investigations into the pathological mechanisms of FRDA have revealed the central role of frataxin deficiency and the subsequent lack of transcription factor Nrf2. Consequently, the Nrf2 activators discussed here as well as the several treatments in development focus on reversing the oxidative stress environment caused by frataxin deficiency. While the discussed orphan drugs show promise in the treatment of FRDA, further investigations must be conducted in order to ensure the efficacy and safety of such drugs, as well as to determine even more therapeutic options.
Monday, October 14, 2019
Reata Announces Positive Topline Results from the MOXIe Registrational Trial of Omaveloxolone in Patients with Friedreich’s Ataxia
ACHIEVED PRIMARY ENDPOINT OF STATISTICALLY SIGNIFICANT IMPROVEMENT IN MFARS COMPARED TO PLACEBO AFTER 48 WEEKS OF TREATMENT
CONFERENCE CALL WITH MANAGEMENT SCHEDULED FOR OCTOBER 15, 2019, AT 8:00 AM ET
IRVING, Texas, Oct. 14, 2019 (GLOBE NEWSWIRE) -- Reata Pharmaceuticals, Inc. (Nasdaq: RETA), a clinical-stage biopharmaceutical company, announced today that the registrational Part 2 portion of the MOXIe Phase 2 trial of omaveloxolone in patients with Friedreich’s ataxia (FA) met its primary endpoint of change in the modified Friedreich’s Ataxia Rating Scale (mFARS) relative to placebo after 48 weeks of treatment. Patients treated with omaveloxolone (150 mg/day) demonstrated a statistically significant, placebo-corrected 2.40 point improvement in mFARS after 48 weeks of treatment (p=0.014). Omaveloxolone treatment was generally reported to be well-tolerated. Based on these positive results, and subject to discussions with regulatory authorities, the company plans to proceed with the submission of regulatory filings for marketing approval in the United States and internationally.
CONFERENCE CALL WITH MANAGEMENT SCHEDULED FOR OCTOBER 15, 2019, AT 8:00 AM ET
IRVING, Texas, Oct. 14, 2019 (GLOBE NEWSWIRE) -- Reata Pharmaceuticals, Inc. (Nasdaq: RETA), a clinical-stage biopharmaceutical company, announced today that the registrational Part 2 portion of the MOXIe Phase 2 trial of omaveloxolone in patients with Friedreich’s ataxia (FA) met its primary endpoint of change in the modified Friedreich’s Ataxia Rating Scale (mFARS) relative to placebo after 48 weeks of treatment. Patients treated with omaveloxolone (150 mg/day) demonstrated a statistically significant, placebo-corrected 2.40 point improvement in mFARS after 48 weeks of treatment (p=0.014). Omaveloxolone treatment was generally reported to be well-tolerated. Based on these positive results, and subject to discussions with regulatory authorities, the company plans to proceed with the submission of regulatory filings for marketing approval in the United States and internationally.
Sunday, October 13, 2019
Iron–Sulfur Cluster Metabolism Impacts Iron Homeostasis, Ferroptosis Sensitivity, and Human Disease
Vladislav O. SviderskiyErdem M. TerziRichard Possemato, Ferroptosis in Health and Disease. Springer, Cham. doi:10.1007/978-3-030-26780-3_12
We ask whether dysregulation of ISC synthesis, observed in multiple pathological settings including neurodegenerative diseases such as Friedreich’s Ataxia, sideroblastic anemia, and cancer, leads to pathology as a result of ferroptosis.
We ask whether dysregulation of ISC synthesis, observed in multiple pathological settings including neurodegenerative diseases such as Friedreich’s Ataxia, sideroblastic anemia, and cancer, leads to pathology as a result of ferroptosis.
Saturday, October 12, 2019
Reata Pharmaceuticals Reacquires Rights From AbbVie to Develop and Commercialize Bardoxolone Methyl, Omaveloxolone, and All Next-Generation Nrf2 Activators
IRVING, Texas, Oct. 10, 2019 (GLOBE NEWSWIRE) — Reata Pharmaceuticals, Inc. (Nasdaq: RETA), a clinical-stage biopharmaceutical company, today announced the reacquisition of development, manufacturing and commercialization rights concerning its proprietary Nrf2 activator product platform originally licensed to AbbVie, Inc. (AbbVie) for territories outside of the United States with respect to bardoxolone methyl (bardoxolone) and worldwide with respect to omaveloxolone and other next-generation Nrf2 activators. As a result, Reata now possesses exclusive, worldwide rights to develop, manufacture and commercialize bardoxolone methyl (bardoxolone), omaveloxolone, and all other next-generation Nrf2 activators, excluding certain Asian markets for bardoxolone which are licensed to Kyowa Kirin Co., Ltd.
Friday, October 11, 2019
Induced pluripotent stem cells-derived neurons from patients with Friedreich ataxia exhibit differential sensitivity to resveratrol and nicotinamide
Pauline Georges, Maria-Gabriela Boza-Moran, Jacqueline Gide, Georges Arielle Pêche, Benjamin Forêt, Aurélien Bayot, Pierre Rustin, Marc Peschanski, Cécile Martinat & Laetitia Aubry ; Scientific Reports volume 9, Article number: 14568 (2019) doi:10.1038/s41598-019-49870-y
By comparing the effects of both molecules on different cell types that may be considered to be non-relevant for the disease, such as fibroblasts, or more relevant to the disease, such as neurons differentiated from iPSCs, a differential response was observed; this response suggests the importance of developing more predictive in vitro systems for drug discovery. Our results demonstrate the value of utilizing human iPSCs early in drug discovery to improve translational predictability.
By comparing the effects of both molecules on different cell types that may be considered to be non-relevant for the disease, such as fibroblasts, or more relevant to the disease, such as neurons differentiated from iPSCs, a differential response was observed; this response suggests the importance of developing more predictive in vitro systems for drug discovery. Our results demonstrate the value of utilizing human iPSCs early in drug discovery to improve translational predictability.
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