J.-M. Vallat, C. Goizet, M. Tazir, P. Couratier, L. Magy, S. Mathis. Revue Neurologique, Available online 27 May 2016, ISSN 0035-3787, doi:org/10.1016/j.neurol.2016.04.005.
Neurodegenerative disorders represent a wide group of diseases affecting the central and/or peripheral nervous system. Many of these disorders were described in the 19th century, but our genetic knowledge of them is recent (over the past 25 years). However, the continual discovery of disease-causing gene mutations has led to difficulties in the classification of these diseases.
The nomenclature used in each case also requires the name of the mutated gene: for example Friedreich’s ataxia becomes ‘‘AR-CA-FXN’’. Nevertheless, these designations could allow some exceptions to be retained, such as names that are very well known, such as Friedreich’s ataxia and ataxia–telangiectasia.
Saturday, June 11, 2016
Friday, June 10, 2016
NRF2 activators: how do they work and how advanced is their clinical use?
Antonio Cuadrado, Free Radical Biology and Medicine, Volume 96, Supplement 1, July 2016, Pages S6-S7, ISSN 0891-5849, doi:10.1016/j.freeradbiomed.2016.04.043
The transcription factor, nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a master regulator of cell homeostasis that regulates the expression of antioxidant and cytoprotective genes. The synthetic triterpenoid CDDO-methyl ester (also known as bardoxolone methyl) is being studied for therapy of diabetic nephropathy, pulmonary arterial hypertension, melanoma and Friedreich ataxia.
The transcription factor, nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a master regulator of cell homeostasis that regulates the expression of antioxidant and cytoprotective genes. The synthetic triterpenoid CDDO-methyl ester (also known as bardoxolone methyl) is being studied for therapy of diabetic nephropathy, pulmonary arterial hypertension, melanoma and Friedreich ataxia.
Thursday, June 9, 2016
Responsible implementation of expanded carrier screening
Lidewij Henneman, Pascal Borry, Davit Chokoshvili, Martina C Cornel, Carla G van El, Francesca Forzano, Alison Hall, Heidi C Howard, Sandra Janssens, Hülya Kayserili, Phillis Lakeman, Anneke Lucassen, Sylvia A Metcalfe, Lovro Vidmar, Guido de Wert, Wybo J Dondorp and Borut Peterlin on behalf of the European Society of Human Genetics (ESHG).European Journal of Human Genetics (2016) 24, e1–e12; doi:10.1038/ejhg.2015.271; published online 16 March 2016
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
There are currently 1300 known recessive (autosomal and X-linked) diseases and about 100 of these have a prevalence of >1/100 000. Several important conditions, for example, Duchenne/Becker muscular dystrophy and Friedreich ataxia are not included in any of the commercial panels, presumably due to technological limitations of the microarray-based testing approach (eg, trinucleotide repeat mutations). We propose that, pending convincing evidence to the contrary, retaining a ‘serious congenital and childhood onset disorders’ scope is important in panel design.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
There are currently 1300 known recessive (autosomal and X-linked) diseases and about 100 of these have a prevalence of >1/100 000. Several important conditions, for example, Duchenne/Becker muscular dystrophy and Friedreich ataxia are not included in any of the commercial panels, presumably due to technological limitations of the microarray-based testing approach (eg, trinucleotide repeat mutations). We propose that, pending convincing evidence to the contrary, retaining a ‘serious congenital and childhood onset disorders’ scope is important in panel design.
Wednesday, June 8, 2016
Histone deacetylase inhibitors modulating non-epigenetic players: The novel molecular targets for therapeutic intervention
Shabir Ahmad Ganai. Current Drug Targets, Volume 17 DOI: 10.2174/1389450117666160527143257
Emerging evidences suggest that acetylation of non-histone proteins plays a critical role in various cellular processes including mRNA stability, protein localization and degradation. Abnormal turnover or expression of non-histone proteins like nuclear factor- kappaB (NF-кB), heat shock protein 90 (HSP90) and frataxin fuels various diseases including cancer.
Emerging evidences suggest that acetylation of non-histone proteins plays a critical role in various cellular processes including mRNA stability, protein localization and degradation. Abnormal turnover or expression of non-histone proteins like nuclear factor- kappaB (NF-кB), heat shock protein 90 (HSP90) and frataxin fuels various diseases including cancer.
Tuesday, June 7, 2016
Quantifying benefit-risk preferences for new medicines in rare disease patients and caregivers
T. Morel, S. Aymé, D. Cassiman, S. Simoens, M. Morgan and M. Vandebroek. Orphanet Journal of Rare Diseases 2016 DOI: 10.1186/s13023-016-0444-9
This study aimed to explore what they consider of value when choosing between hypothetical therapeutic options and to quantify both their benefit-risk preferences and the influence of disease context.
Our study data confirmed that patients and their caregivers were willing to accept greater risk or side effects associated with a new medicine, for instance, in the hope for some extra chance in drug response or greater health improvement potential. Attitudes about benefit-risk may change over time with disease progression or context of care.
In that context, we believe that patients and caregivers should be increasingly involved as active research partners in the development of clinical outcomes assessments – including patient-reported outcomes (PRO) measures – that directly evaluate how the patient feels, functions or survives. If a treatment effect is not meaningful to the patient, it is not a benefit to the patient.
Open Access
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)
This study aimed to explore what they consider of value when choosing between hypothetical therapeutic options and to quantify both their benefit-risk preferences and the influence of disease context.
Our study data confirmed that patients and their caregivers were willing to accept greater risk or side effects associated with a new medicine, for instance, in the hope for some extra chance in drug response or greater health improvement potential. Attitudes about benefit-risk may change over time with disease progression or context of care.
In that context, we believe that patients and caregivers should be increasingly involved as active research partners in the development of clinical outcomes assessments – including patient-reported outcomes (PRO) measures – that directly evaluate how the patient feels, functions or survives. If a treatment effect is not meaningful to the patient, it is not a benefit to the patient.
Open Access
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)
Monday, June 6, 2016
The hereditary ataxias: Where are we now? Four decades of local research
D C Smith, L J Greenberg, A Bryer. South African Medical Journal 2016;106(6):S38. DOI:10.7196/SAMJ.2016.v106i6.10989
The hereditary ataxias have been studied at the University of Cape Town for more than 40 years, following from initial clinical investigations by Beighton and colleagues in the early 1970s.
Thirty-seven of these individuals (from 30 families) had molecularly confirmed FRDA. To the best of our knowledge, no individuals of indigenous black African ethnic origin have been given a confirmed molecular diagnosis of FRDA. The vast majority of confirmed FRDA patients in SA are of European ancestry, along with a single family of Indian origin.
The hereditary ataxias have been studied at the University of Cape Town for more than 40 years, following from initial clinical investigations by Beighton and colleagues in the early 1970s.
Thirty-seven of these individuals (from 30 families) had molecularly confirmed FRDA. To the best of our knowledge, no individuals of indigenous black African ethnic origin have been given a confirmed molecular diagnosis of FRDA. The vast majority of confirmed FRDA patients in SA are of European ancestry, along with a single family of Indian origin.
Sunday, June 5, 2016
The significance of intercalated discs in the pathogenesis of Friedreich cardiomyopathy
Arnulf H. Koeppen, Alyssa B. Becker, Paul J. Feustel, Benjamin B. Gelman, Joseph E. Mazurkiewicz. Journal of the Neurological Sciences, Available online 4 June 2016, ISSN 0022-510X, doi: 10.1016/j.jns.2016.06.006.
Highlights
-The most frequent cause of death in Friedreich ataxia is cardiomyopathy
-Abnormal intercalated discs contribute to Friedreich cardiomyopathy
-Intercalated discs and gap junctions are normal in long-surviving patients
Highlights
-The most frequent cause of death in Friedreich ataxia is cardiomyopathy
-Abnormal intercalated discs contribute to Friedreich cardiomyopathy
-Intercalated discs and gap junctions are normal in long-surviving patients
Saturday, June 4, 2016
Aspects éthico-sociétaux liés à l’utilisation de la technique d’édition du génome CRISPR-Cas9 (FR)
INSERM (Institut National de la santé et de la recherche médicale). Comité éthique Inserm février 2016.
Saisine concernant les questions liées au développement de la technologie CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9.
L’ingénierie du génome ou « Editer le génome » (traduit ainsi de l’anglais « genome editing ») consiste à ajouter, enlever, modifier une ou quelques bases dans une séquence d’ADN. Si la séquence correspond à un gène, la conséquence en sera la modification d’expression de ce gène, soit son « invalidation » (perte de fonction, knock-down), soit la modification de la séquence protéique de la protéine qu’il code et dans certains cas le changement d’activité ou de localisation ou de durée de vie ou au contraire la correction d’une fonction altérée, selon le contexte biologique.
De quoi s’agit-il ?, CRISPR-Ccas 9 est en quelque sorte un ciseau moléculaire capable d’induire une cassure double brin de l’ADN en un site choisi du génome.
Le principe de précaution peut être invoqué lorsqu’un phénomène, un produit ou un procédé peut avoir des effets potentiellement dangereux, identifiés par une évaluation scientifique et objective, si cette évaluation ne permet pas de déterminer le risque avec suffisamment de certitude.
Saisine concernant les questions liées au développement de la technologie CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9.
L’ingénierie du génome ou « Editer le génome » (traduit ainsi de l’anglais « genome editing ») consiste à ajouter, enlever, modifier une ou quelques bases dans une séquence d’ADN. Si la séquence correspond à un gène, la conséquence en sera la modification d’expression de ce gène, soit son « invalidation » (perte de fonction, knock-down), soit la modification de la séquence protéique de la protéine qu’il code et dans certains cas le changement d’activité ou de localisation ou de durée de vie ou au contraire la correction d’une fonction altérée, selon le contexte biologique.
De quoi s’agit-il ?, CRISPR-Ccas 9 est en quelque sorte un ciseau moléculaire capable d’induire une cassure double brin de l’ADN en un site choisi du génome.
Le principe de précaution peut être invoqué lorsqu’un phénomène, un produit ou un procédé peut avoir des effets potentiellement dangereux, identifiés par une évaluation scientifique et objective, si cette évaluation ne permet pas de déterminer le risque avec suffisamment de certitude.
Friday, June 3, 2016
10 top patient groups oppose REGROW Act that would gut stem cell oversight
The Niche, Knoepfler lab stem cell blog. June 1, 2016.
The REGROW Act would drastically weaken FDA regulation of experimental stem cell therapies.
Patient Groups Opposing REGROW
Cystic Fibrosis Foundation
Friedreich’s Ataxia Research Alliance
Friends of Cancer Research
Global Genes
Michael J. Fox Foundation for Parkinson’s Research
Myotonic Dystrophy Foundation
National MS Society
National Organization for Rare Disorders
National Patient Advocate Foundation
Prevent Cancer Foundation
The REGROW Act would drastically weaken FDA regulation of experimental stem cell therapies.
Patient Groups Opposing REGROW
Cystic Fibrosis Foundation
Friedreich’s Ataxia Research Alliance
Friends of Cancer Research
Global Genes
Michael J. Fox Foundation for Parkinson’s Research
Myotonic Dystrophy Foundation
National MS Society
National Organization for Rare Disorders
National Patient Advocate Foundation
Prevent Cancer Foundation
Thursday, June 2, 2016
US FDA Grants Orphan Drug Designation for Retrotope's RT001 in the Treatment of Friedreich's Ataxia
LOS ALTOS, CA -- (Marketwired) -- 06/01/16 -- Retrotope announced today that the U.S. Food and Drug Administration (FDA) Office of Orphan Products Development granted orphan drug designation for its stabilized fatty acid drug (RT001) for the treatment of Friedreich's ataxia (FA).
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