Alejandro M. Armas, Manuel Balparda, Agustina Terenzi, Maria V. Busi, Maria A. Pagani and Diego F. Gomez-Casati; Plants 2020, 9(9), 1171, doi:10.3390/plants9091171 (registering DOI) In plants, the cysteine desulfurase (AtNFS1) and frataxin (AtFH) are involved in the formation of Fe-S groups in mitochondria, specifically, in Fe and sulfur loading onto scaffold proteins, and the subsequent formation of the mature Fe-S cluster. We found that the small mitochondrial chaperone, AtISD11, and AtFH are positive regulators for AtNFS1 activity in Arabidopsis. Moreover, when the three proteins were incubated together, a stronger attenuation of the Fenton reaction was observed compared to that observed with AtFH alone. Using pull-down assays, we found that these three proteins physically interact, and sequence alignment and docking studies showed that several amino acid residues reported as critical for the interaction of their human homologous are conserved. Our results suggest that AtFH, AtNFS1 and AtISD11 form a multiprotein complex that could be involved in different stages of the iron–sulfur cluster (ISC) pathway in plant mitochondria.
Friday, September 11, 2020
Thursday, September 10, 2020
Rare Disease Trials Require Interactions With KOLs, Patients, & Regulators
Clinical Leader, September 9, 2020; Chief Editor: Ed Miseta Minoryx Therapeutics is a small biotech hoping to bring new hope to patients suffering from orphan CNS diseases. The company of 25 employees was founded in 2011 and is seeking treatments for diseases with a high unmet medical need. The company’s leading program is leriglitazone, currently in development for multiple CNS disorders. Leriglitazone is a small-molecule selective PPAR gamma agonist.
Another example is the company’s Friedreich’s Ataxia study, which required a different interaction with regulators. In that case, the disease was better known to physicians and Minoryx was able to locate more data on the progression of the disease. The company designed a Phase 2 trial and, upon completion of that study, will discuss the results with regulators to determine future steps.
Tuesday, September 8, 2020
Ataxia: Hope starts with measurement
The Florey Institute of Neuroscience and Mental Health. News and media. 03 Sep 2020.
The team will be developing a prototype device to measure ataxia thanks to funding received from the Biomedical Translation Bridge program administered by MTP Connect.
The $500,000 in funding was announced today by the Minister for Health, the Hon. Greg Hunt MP, with US-based advocacy organisation Friedreich Ataxia Research Alliance (FARA) confirming they will match the government’s investment.
“Whilst there are multiple treatments in development for heredity forms of ataxia in particular, without clinicians being able to make objective measurements for the condition it makes it difficult to understand the effectiveness of these. We believe that developing a device which uses sensors and sophisticated algorithms to assess ataxia progression will allow these treatments to be fast tracked,” said Associate Professor Corben.
The team will be developing a prototype device to measure ataxia thanks to funding received from the Biomedical Translation Bridge program administered by MTP Connect.
The $500,000 in funding was announced today by the Minister for Health, the Hon. Greg Hunt MP, with US-based advocacy organisation Friedreich Ataxia Research Alliance (FARA) confirming they will match the government’s investment.
“Whilst there are multiple treatments in development for heredity forms of ataxia in particular, without clinicians being able to make objective measurements for the condition it makes it difficult to understand the effectiveness of these. We believe that developing a device which uses sensors and sophisticated algorithms to assess ataxia progression will allow these treatments to be fast tracked,” said Associate Professor Corben.
Molecular and Cellular Substrates for the Friedreich Ataxia. Significance of Contactin Expression and of Antioxidant Administration
Bizzoca, A.; Caracciolo, M.; Corsi, P.; Magrone, T.; Jirillo, E.; Gennarini, G.; Molecules 2020, 25, 4085. doi:10.3390/molecules25184085
In this study, the neural phenotype is explored in rodent models of the spinocerebellar disorder known as the Friedreich Ataxia (FA), which results from mutations within the gene encoding the Frataxin mitochondrial protein. For this, the M12 line, bearing a targeted mutation, which disrupts the Frataxin gene exon 4 was used, together with the M02 line, which, in addition, is hemizygous for the human Frataxin gene mutation (Pook transgene), implying the occurrence of 82–190 GAA repeats within its first intron. The mutant mice phenotype was compared to the one of wild type littermates in regions undergoing differential profiles of neurogenesis, including the cerebellar cortex and the spinal cord by using neuronal (β-tubulin) and glial (Glial Fibrillary Acidic Protein) markers as well as the Contactin 1 axonal glycoprotein, involved in neurite growth control. Morphological/morphometric analyses revealed that while in Frataxin mutant mice the neuronal phenotype was significantly counteracted, a glial upregulation occurred at the same time. Furthermore, Contactin 1 downregulation suggested that changes in the underlying gene contributed to the disorder pathogenesis. Therefore, the FA phenotype implies an alteration of the developmental profile of neuronal and glial precursors. Finally, epigallocatechin gallate polyphenol administration counteracted the disorder, indicating protective effects of antioxidant administration.
In this study, the neural phenotype is explored in rodent models of the spinocerebellar disorder known as the Friedreich Ataxia (FA), which results from mutations within the gene encoding the Frataxin mitochondrial protein. For this, the M12 line, bearing a targeted mutation, which disrupts the Frataxin gene exon 4 was used, together with the M02 line, which, in addition, is hemizygous for the human Frataxin gene mutation (Pook transgene), implying the occurrence of 82–190 GAA repeats within its first intron. The mutant mice phenotype was compared to the one of wild type littermates in regions undergoing differential profiles of neurogenesis, including the cerebellar cortex and the spinal cord by using neuronal (β-tubulin) and glial (Glial Fibrillary Acidic Protein) markers as well as the Contactin 1 axonal glycoprotein, involved in neurite growth control. Morphological/morphometric analyses revealed that while in Frataxin mutant mice the neuronal phenotype was significantly counteracted, a glial upregulation occurred at the same time. Furthermore, Contactin 1 downregulation suggested that changes in the underlying gene contributed to the disorder pathogenesis. Therefore, the FA phenotype implies an alteration of the developmental profile of neuronal and glial precursors. Finally, epigallocatechin gallate polyphenol administration counteracted the disorder, indicating protective effects of antioxidant administration.
Sunday, September 6, 2020
Registries for orphan drugs: generating evidence or marketing tools?
Carla E. M. Hollak, Sandra Sirrs, Sibren van den Berg, Vincent van der Wel, Mirjam Langeveld, Hanka Dekker, Robin Lachmann & Saco J. de Visser; Orphanet J Rare Dis 15, 235 (2020). doi:10.1186/s13023-020-01519-0
Independent disease registries for pre-and post-approval of novel treatments for rare diseases are increasingly important for healthcare professionals, patients, regulators and the pharmaceutical industry. Current registries for rare diseases to evaluate orphan drugs are mainly set up and owned by the pharmaceutical industry which leads to unacceptable conflicts of interest. To ensure independence from commercial interests, disease registries should be set up and maintained by healthcare professionals and patients. Public funding should be directed towards an early establishment of international registries for orphan diseases, ideally well before novel treatments are introduced. Regulatory bodies should insist on the use of data from independent disease registries rather than company driven, drug-oriented registries.
Independent disease registries for pre-and post-approval of novel treatments for rare diseases are increasingly important for healthcare professionals, patients, regulators and the pharmaceutical industry. Current registries for rare diseases to evaluate orphan drugs are mainly set up and owned by the pharmaceutical industry which leads to unacceptable conflicts of interest. To ensure independence from commercial interests, disease registries should be set up and maintained by healthcare professionals and patients. Public funding should be directed towards an early establishment of international registries for orphan diseases, ideally well before novel treatments are introduced. Regulatory bodies should insist on the use of data from independent disease registries rather than company driven, drug-oriented registries.
Saturday, September 5, 2020
Broad Institute launches new effort to study rare neuromuscular disorder
Broad Institute, NEWS / 09.3.20. By Leah Eisenstadt.
A new research and drug discovery effort at the Broad Institute of MIT and Harvard is taking aim at the rare, inherited movement disorder Friedreich’s ataxia (FA), which causes progressive damage to the nervous system. FA arises from genetic mutations that lead to dysfunction of the cell’s energy-producing organelles called mitochondria.
“The goal of the Friedreich's Ataxia Accelerator is to nucleate a small group of investigators who will bring the power of genomics to this debilitating disease,” said Mootha, who is also a Howard Hughes Medical Institute investigator and professor of medicine at Harvard Medical School and Massachusetts General Hospital.
A new research and drug discovery effort at the Broad Institute of MIT and Harvard is taking aim at the rare, inherited movement disorder Friedreich’s ataxia (FA), which causes progressive damage to the nervous system. FA arises from genetic mutations that lead to dysfunction of the cell’s energy-producing organelles called mitochondria.
“The goal of the Friedreich's Ataxia Accelerator is to nucleate a small group of investigators who will bring the power of genomics to this debilitating disease,” said Mootha, who is also a Howard Hughes Medical Institute investigator and professor of medicine at Harvard Medical School and Massachusetts General Hospital.
Friday, September 4, 2020
Impact of the therapeutic positioning report in the P&R process in Spain: analysis of orphan drugs approved by the European Commission and reimbursed in Spain from 2003 to 2019
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.
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.
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.
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