Xavier Badia, Tania Vico, John Shepherd, Alicia Gil, José Luis Poveda-Andrés & César Hernández; Orphanet J Rare Dis 15, 224 (2020). doi:10.1186/s13023-020-01507-4
This study shows that the therapeutic positioning report plays a key role in the pricing and reimbursement process in Spain. A positive conclusion of the therapeutic positioning report seems to favourably affect pricing and reimbursement decisions in Spain and, since its introduction, has also contributed to reduce pricing and reimbursement approval timelines in Spain.
Friday, September 4, 2020
Thursday, September 3, 2020
AveXis renamed Novartis Gene Therapies, signifying the growing importance of gene therapy to Novartis corporate strategy
Novartis, Sep 02, 2020
Novartis has renamed the previously acquired AveXis to Novartis Gene Therapies. The change signifies the growing importance of gene therapy to building a leading, focused medicines company with advanced therapy platforms.
The change to Novartis Gene Therapies is the natural evolution as the company scales up to deliver Zolgensma globally and expand its reach via a robust pipeline of AAV-based gene therapies for rare genetic diseases including investigational treatments for Rett syndrome, a genetic form of amyotrophic lateral sclerosis (ALS) and Friedreich’s ataxia. Novartis Gene Therapies also establishes a seamless global presence for Zolgensma and the gene therapies to come. Instead of alternating between the AveXis and Novartis umbrella brands by market, the company comes together under one banner as a unified entity.
Novartis has renamed the previously acquired AveXis to Novartis Gene Therapies. The change signifies the growing importance of gene therapy to building a leading, focused medicines company with advanced therapy platforms.
The change to Novartis Gene Therapies is the natural evolution as the company scales up to deliver Zolgensma globally and expand its reach via a robust pipeline of AAV-based gene therapies for rare genetic diseases including investigational treatments for Rett syndrome, a genetic form of amyotrophic lateral sclerosis (ALS) and Friedreich’s ataxia. Novartis Gene Therapies also establishes a seamless global presence for Zolgensma and the gene therapies to come. Instead of alternating between the AveXis and Novartis umbrella brands by market, the company comes together under one banner as a unified entity.
Reata Announces the Presentation of the Pivotal MOXIe Part 2 Study of Omaveloxolone in Friedreich’s Ataxia at the American Academy of Neurology
September 03, 2020 06:45 ET | Source: Reata Pharmaceuticals, Inc.
PLANO, Texas, Sept. 03, 2020 (GLOBE NEWSWIRE) -- Reata Pharmaceuticals, Inc. (Nasdaq: RETA) (“Reata,” the “Company,” or “we”), a clinical-stage biopharmaceutical company, today announced the forthcoming presentation of efficacy and safety results from the pivotal MOXIe Part 2 study, a randomized, double-blind, placebo-controlled trial of omaveloxolone in Friedreich’s ataxia.
The presentation will take place on September 24, 2020 as part of the 2020 Emerging Science presentations hosted by the American Academy of Neurology (AAN). David Lynch, M.D., Ph.D., will present the data. Dr. Lynch is an attending physician at the Children’s Hospital of Philadelphia (CHOP), professor of neurology at the Perelman School of Medicine at the University of Pennsylvania, and the principal investigator of the MOXIe study.
Separately, Dr. Lynch will present the results of the MOXIe Part 2 study at the FARA 2020 Biomarker & Clinical Endpoint Meetin
PLANO, Texas, Sept. 03, 2020 (GLOBE NEWSWIRE) -- Reata Pharmaceuticals, Inc. (Nasdaq: RETA) (“Reata,” the “Company,” or “we”), a clinical-stage biopharmaceutical company, today announced the forthcoming presentation of efficacy and safety results from the pivotal MOXIe Part 2 study, a randomized, double-blind, placebo-controlled trial of omaveloxolone in Friedreich’s ataxia.
The presentation will take place on September 24, 2020 as part of the 2020 Emerging Science presentations hosted by the American Academy of Neurology (AAN). David Lynch, M.D., Ph.D., will present the data. Dr. Lynch is an attending physician at the Children’s Hospital of Philadelphia (CHOP), professor of neurology at the Perelman School of Medicine at the University of Pennsylvania, and the principal investigator of the MOXIe study.
Separately, Dr. Lynch will present the results of the MOXIe Part 2 study at the FARA 2020 Biomarker & Clinical Endpoint Meetin
High levels of frataxin overexpression leads to mitochondrial and cardiac toxicity in mouse models
Brahim Belbellaa, Laurence Reutenauer, Nadia Messaddeq, Laurent Monassier, Hélène Puccio; Molecular Therapy - Methods & Clinical Development, 2020, doi:10.1016/j.omtm.2020.08.018.
this study underlines the need, during the development of gene therapy approaches, to consider appropriately vector expression level, long term safety and biomarkers to monitor such events.
this study underlines the need, during the development of gene therapy approaches, to consider appropriately vector expression level, long term safety and biomarkers to monitor such events.
Wednesday, September 2, 2020
The uses of resveratrol for neurological diseases treatment and insights for nanotechnology based-drug delivery systems
Bruno Fonseca-Santos, Marlus Chorilli, International Journal of Pharmaceutics, 2020, 119832, doi:10.1016/j.ijpharm.2020.119832.
Due to the insolubility of this compound; the use of nanotechnology-based systems has been proposed for the incorporation of RES and RES-loaded nanocarriers have been designed for intranasal administration, oral or parenteral routes to deliver it to the brain. In general, these nanosystems have shown to be effective in many studies, pharmacological and pharmacokinetic assays, as well as some cell studies. The outcomes show that RES has been reported in human clinical trials for some neurological diseases, although no studies were performed in humans using nanocarriers, animal and/or cellular models have been reported to show good results regarding therapeutics on neurological diseases. Thus, the use of this nutraceutical has shown true for neurological diseases and its loading into nanocarriers displaying good results on the stability, delivery and targeting to the brain.
Due to the insolubility of this compound; the use of nanotechnology-based systems has been proposed for the incorporation of RES and RES-loaded nanocarriers have been designed for intranasal administration, oral or parenteral routes to deliver it to the brain. In general, these nanosystems have shown to be effective in many studies, pharmacological and pharmacokinetic assays, as well as some cell studies. The outcomes show that RES has been reported in human clinical trials for some neurological diseases, although no studies were performed in humans using nanocarriers, animal and/or cellular models have been reported to show good results regarding therapeutics on neurological diseases. Thus, the use of this nutraceutical has shown true for neurological diseases and its loading into nanocarriers displaying good results on the stability, delivery and targeting to the brain.
Tuesday, September 1, 2020
An Optimally Weighted User- and Item-based Collaborative Filtering Approach to Predicting Baseline Data for Friedreich’s Ataxia Patients
Wenbin Yue, Zidong Wang, Weibo Liu, Bo Tian, Stanislao Lauria, Xiaohui Liu, Neurocomputing, 2020, doi:10.1016/j.neucom.2020.08.031.
In this paper, a modified collaborative filtering (MCF) algorithm with improved performance is developed for recommendation systems with application in predicting baseline data of Friedreich’s Ataxia (FRDA) patients. The proposed MCF algorithm combines the individual merits of both the user-based collaborative filtering (UBCF) method and the item-based collaborative filtering (IBCF) method, where both the positively and negatively correlated neighbors are taken into account. The weighting parameters are introduced to quantify the degrees of utilizations of the UBCF and IBCF methods in the rating prediction, and the particle swarm optimization algorithm is applied to optimize the weighting parameters in order to achieve an adequate tradeoff between the positively and negatively correlated neighbors in terms of predicting the rating values. To demonstrate the prediction performance of the proposed MCF algorithm, the developed MCF algorithm is employed to assist with the baseline data collection for the FRDA patients. The effectiveness of the proposed MCF algorithm is confirmed by extensive experiments and, furthermore, it is shown that our algorithm outperforms some conventional approaches.
In this paper, a modified collaborative filtering (MCF) algorithm with improved performance is developed for recommendation systems with application in predicting baseline data of Friedreich’s Ataxia (FRDA) patients. The proposed MCF algorithm combines the individual merits of both the user-based collaborative filtering (UBCF) method and the item-based collaborative filtering (IBCF) method, where both the positively and negatively correlated neighbors are taken into account. The weighting parameters are introduced to quantify the degrees of utilizations of the UBCF and IBCF methods in the rating prediction, and the particle swarm optimization algorithm is applied to optimize the weighting parameters in order to achieve an adequate tradeoff between the positively and negatively correlated neighbors in terms of predicting the rating values. To demonstrate the prediction performance of the proposed MCF algorithm, the developed MCF algorithm is employed to assist with the baseline data collection for the FRDA patients. The effectiveness of the proposed MCF algorithm is confirmed by extensive experiments and, furthermore, it is shown that our algorithm outperforms some conventional approaches.
Monday, August 31, 2020
Plasma and red blood cell membrane accretion and pharmacokinetics of RT001 (bis-allylic 11,11-D2-linoleic acid ethyl ester) during long term dosing in patients
J. Thomas Brenna, Genevieve James, Mark Midei, Frederic Heerinckx, Paldeep Atwal, Peter Milner, Karsten Schmidt, Lex van der Ploeg, Robert Fielding, Mikhail S. Shchepinov, Journal of Pharmaceutical Sciences, 2020, doi:10.1016/j.xphs.2020.08.019.
RT001 is the di-deutero isotopologue of linoleic acid ethyl ester (D2-LA). Resistance to oxidative damage at the carbon-deuterium bond depends upon the concentration of D2-LA as a percentage of total LA. We report here on the plasma and red cell (RBC) pharmacokinetics (PK) of D2-LA, and its metabolite 13,13-D2-arachidonic acid (D2-AA), in patients with multiple neurodegenerative diseases (total of 59 participants). In Friedreich’s ataxia patients, D2-LA was absorbed and transported similarly to dietary LA, peaking at about 6 h after oral dosing. Plasma D2-LA concentrations approached steady state after 28 days of dosing. After 6 months of daily dosing in subjects with other disorders, D2-LA and D2-AA levels were at or above the 20% of total (D2-LA/ total LA, or D2-AA/ total AA) therapeutic targets for most subjects. We conclude that chronic dosing of RT001 and associated dietary guidance can be maintained over many months to achieve target plasma and RBC levels, forming a basis for therapeutic dosing across a broad range of conditions. RT001 has been safe and well-tolerated in 59 different participants treated across 10 different neurodegenerative diseases in multiple clinical trials for up to 36 months with no significant drug related adverse events limiting use.
RT001 is the di-deutero isotopologue of linoleic acid ethyl ester (D2-LA). Resistance to oxidative damage at the carbon-deuterium bond depends upon the concentration of D2-LA as a percentage of total LA. We report here on the plasma and red cell (RBC) pharmacokinetics (PK) of D2-LA, and its metabolite 13,13-D2-arachidonic acid (D2-AA), in patients with multiple neurodegenerative diseases (total of 59 participants). In Friedreich’s ataxia patients, D2-LA was absorbed and transported similarly to dietary LA, peaking at about 6 h after oral dosing. Plasma D2-LA concentrations approached steady state after 28 days of dosing. After 6 months of daily dosing in subjects with other disorders, D2-LA and D2-AA levels were at or above the 20% of total (D2-LA/ total LA, or D2-AA/ total AA) therapeutic targets for most subjects. We conclude that chronic dosing of RT001 and associated dietary guidance can be maintained over many months to achieve target plasma and RBC levels, forming a basis for therapeutic dosing across a broad range of conditions. RT001 has been safe and well-tolerated in 59 different participants treated across 10 different neurodegenerative diseases in multiple clinical trials for up to 36 months with no significant drug related adverse events limiting use.
Monday, August 24, 2020
Friedreich Ataxia: current state-of-the-art, and future prospects for mitochondrial-focused therapies
Federico V. Pallardó, Giovanni Pagano, Laura R. Rodríguez, Pilar Gonzalez-Cabo, Alex Lyakhovich, Marco Trifuoggi; Translational Research,
2020, doi:10.1016/j.trsl.2020.08.009.
The present mini review is aimed at evaluating the basic and clinical reports on the roles and the use of a set of iron chelators, antioxidants and some cofactors involved in the key mitochondrial functions. Extensive literature has focused on the protective roles of iron chelators, coenzyme Q10 and analogs, and vitamin E, altogether with varying outcomes in clinical studies. Other studies have suggested mitoprotective roles for other mitochondrial cofactors, involved in Krebs cycle, such as alpha-lipoic acid and carnitine, involved in acyl transport across the mitochondrial membrane.
2020, doi:10.1016/j.trsl.2020.08.009.
The present mini review is aimed at evaluating the basic and clinical reports on the roles and the use of a set of iron chelators, antioxidants and some cofactors involved in the key mitochondrial functions. Extensive literature has focused on the protective roles of iron chelators, coenzyme Q10 and analogs, and vitamin E, altogether with varying outcomes in clinical studies. Other studies have suggested mitoprotective roles for other mitochondrial cofactors, involved in Krebs cycle, such as alpha-lipoic acid and carnitine, involved in acyl transport across the mitochondrial membrane.
Sunday, August 23, 2020
Frataxin gene editing rescues Friedreich’s ataxia pathology in dorsal root ganglia organoid-derived sensory neurons
Pietro Giuseppe Mazzara, Sharon Muggeo, Mirko Luoni, Luca Massimino, Mattia Zaghi, Parisa Tajalli-Tehrani Valverde, Simone Brusco, Matteo Jacopo Marzi, Cecilia Palma, Gaia Colasante, Angelo Iannielli, Marianna Paulis, Chiara Cordiglieri, Serena Gea Giannelli, Paola Podini, Cinzia Gellera, Franco Taroni, Francesco Nicassio, Marco Rasponi & Vania Broccoli; Nat Commun 11, 4178 (2020). doi:10.1038/s41467-020-17954-3
These results strongly suggest that removal of the repressed chromatin flanking the GAA tract might contribute to rescue FXN total expression and fully revert the pathological hallmarks of FRDA DRG neurons.
These results strongly suggest that removal of the repressed chromatin flanking the GAA tract might contribute to rescue FXN total expression and fully revert the pathological hallmarks of FRDA DRG neurons.
Saturday, August 22, 2020
Atypical structures of GAA/TTC trinucleotide repeats underlying Friedreich’s ataxia: DNA triplexes and RNA/DNA hybrids
Jiahui Zhang, Ashkan Fakharzadeh, Feng Pan, Christopher Roland, Celeste Sagui; Nucleic Acids Research, gkaa665, doi:10.1093/nar/gkaa665
The authors intended the study to provide a ‘rationale for the discovery and characterization of the non-B DNA regulatory structures involved in the formation of the RNA:DNA interactome’. However, experimental data with molecular resolution for these non-B DNA structures is noticeably scarce. We believe that structural studies such as ours can meaningfully contribute in the creation of such a roadmap.
The authors intended the study to provide a ‘rationale for the discovery and characterization of the non-B DNA regulatory structures involved in the formation of the RNA:DNA interactome’. However, experimental data with molecular resolution for these non-B DNA structures is noticeably scarce. We believe that structural studies such as ours can meaningfully contribute in the creation of such a roadmap.
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