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.
Monday, June 6, 2016
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).
Wednesday, June 1, 2016
Epoetin Alpha Improves Upper-Limb Dexterity in Patients With Friedreich’s Ataxia: Presented at EAN
FirstWord Pharma, By Chris Berrie.
COPENHAGEN, Denmark -- May 31, 2016 -- Epoetin alpha does not modify frataxin levels or improve physical performance in patients with the debilitating, degenerative neuromuscular disorder known as Friedreich’s ataxia, although it progressively ameliorates upper-limb dexterity compared with placebo, according to results presented at the 2nd Congress of the European Academy of Neurology (EAN).
COPENHAGEN, Denmark -- May 31, 2016 -- Epoetin alpha does not modify frataxin levels or improve physical performance in patients with the debilitating, degenerative neuromuscular disorder known as Friedreich’s ataxia, although it progressively ameliorates upper-limb dexterity compared with placebo, according to results presented at the 2nd Congress of the European Academy of Neurology (EAN).
Tuesday, May 31, 2016
Paying for future success in gene therapy
Stuart H. Orkin, Philip Reilly. Science 27 May 2016: Vol. 352, Issue 6289, pp. 1059-1061 DOI: 10.1126/science.aaf4770
OPEN
The authors expect the federal Food and Drug Administration (FDA) will approve at least one gene therapy treatment within the next three years. As a new generation of gene therapy clinical trials shows promise to cure or halt the progression of several rare diseases, the time has come to explore ways to pay for the cutting edge treatments. Noting the potential of gene therapy to be a one-time treatment for rare and serious diseases that otherwise cost hundreds of thousands, if not millions, of dollars in chronic care over a lifetime. The process of developing a new gene therapy treatment and securing FDA approval, they estimate, entails about eight years and direct costs of hundreds of millions of dollars.
OPEN
The authors expect the federal Food and Drug Administration (FDA) will approve at least one gene therapy treatment within the next three years. As a new generation of gene therapy clinical trials shows promise to cure or halt the progression of several rare diseases, the time has come to explore ways to pay for the cutting edge treatments. Noting the potential of gene therapy to be a one-time treatment for rare and serious diseases that otherwise cost hundreds of thousands, if not millions, of dollars in chronic care over a lifetime. The process of developing a new gene therapy treatment and securing FDA approval, they estimate, entails about eight years and direct costs of hundreds of millions of dollars.
Monday, May 30, 2016
Uncovering brain-heart information through advanced signal and image processing.
Philos Trans A Math Phys Eng Sci. 2016 May 13; 374(2067): 20160020. doi: 10.1098/rsta.2016.0020
A recent article in Scientific American (‘A new idea for treating Alzheimer's’)begins with the following sentence: ‘If it's good for the heart, it could also be good for the neurons, astrocytes and oligodendrocytes, cells that make up the main items on the brain's parts list’, suggesting that Alzheimer's disease may be a candidate for combined brain–heart therapeutic approaches. Furthermore, a wide variety of changes in the electrocardiogram, mainly referring to arrhythmias and repolarization, is often observed in the context of neurological disease.
A significant part of the current knowledge on brain–heart interaction as applied to the medical field refers to ‘neurocardiology’. While this discipline is inherently multidimensional, it may be conceptualized as divided into three major categories: the heart's effects on the brain (e.g. cardiac source embolic stroke), the brain's effects on the heart (e.g. neurogenic heart disease) and neurocardiac syndromes (e.g. Friedreich's ataxia).
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/)
A recent article in Scientific American (‘A new idea for treating Alzheimer's’)begins with the following sentence: ‘If it's good for the heart, it could also be good for the neurons, astrocytes and oligodendrocytes, cells that make up the main items on the brain's parts list’, suggesting that Alzheimer's disease may be a candidate for combined brain–heart therapeutic approaches. Furthermore, a wide variety of changes in the electrocardiogram, mainly referring to arrhythmias and repolarization, is often observed in the context of neurological disease.
A significant part of the current knowledge on brain–heart interaction as applied to the medical field refers to ‘neurocardiology’. While this discipline is inherently multidimensional, it may be conceptualized as divided into three major categories: the heart's effects on the brain (e.g. cardiac source embolic stroke), the brain's effects on the heart (e.g. neurogenic heart disease) and neurocardiac syndromes (e.g. Friedreich's ataxia).
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/)
Sunday, May 29, 2016
Inside HDACs with more selective HDAC inhibitors
Joëlle Roche, Philippe Bertrand, European Journal of Medicinal Chemistry, Available online 25 May 2016, ISSN 0223-5234, doi: 10.1016/j.ejmech.2016.05.047.
Inhibitors of histone deacetylases (HDACs) are nowadays part of the therapeutic arsenal mainly against cancers, with four compounds approved by the Food and Drug Administration.During the last five years, several groups have made continuous efforts to improve this class of compounds, designing more selective compounds or compounds with multiple capacities. After a survey of the HDACs biology and structures, this review summarizes the results of the chemists working in this field, and highlights when possible the behaviour of the molecules inside their targets.
Associated disease: Friedreich's ataxia. Partners: Interacts with HDAC7 and HDAC9; DAXX, HDAC10 and DACH1; BCOR, MJD2A/JHDM3A, NRIP1, PRDM6 and SRY, BTBD14B, GLIS2, NR2C1; CBFA2T3 and NKAP; APEX1, MAPK14, ZMYND15, SMRT/NCOR2 and BCL6, INSM1, XBP1 isoform 1, CCAR2, MEF2D, BEND3. Forms a heterologous complex at least with YY1, It may participate in the regulation of transcription through its binding with the zinc-finger transcription factor YY1. Found in a complex with NCOR1 and NCOR2. Component of the N-Cor repressor complex. Component of the Notch corepressor complex. Functions: This protein can also down-regulate p53 function and thus modulate cell growth and apoptosis. This gene is regarded as a potential tumour suppressor gene.
Inhibitors of histone deacetylases (HDACs) are nowadays part of the therapeutic arsenal mainly against cancers, with four compounds approved by the Food and Drug Administration.During the last five years, several groups have made continuous efforts to improve this class of compounds, designing more selective compounds or compounds with multiple capacities. After a survey of the HDACs biology and structures, this review summarizes the results of the chemists working in this field, and highlights when possible the behaviour of the molecules inside their targets.
Associated disease: Friedreich's ataxia. Partners: Interacts with HDAC7 and HDAC9; DAXX, HDAC10 and DACH1; BCOR, MJD2A/JHDM3A, NRIP1, PRDM6 and SRY, BTBD14B, GLIS2, NR2C1; CBFA2T3 and NKAP; APEX1, MAPK14, ZMYND15, SMRT/NCOR2 and BCL6, INSM1, XBP1 isoform 1, CCAR2, MEF2D, BEND3. Forms a heterologous complex at least with YY1, It may participate in the regulation of transcription through its binding with the zinc-finger transcription factor YY1. Found in a complex with NCOR1 and NCOR2. Component of the N-Cor repressor complex. Component of the Notch corepressor complex. Functions: This protein can also down-regulate p53 function and thus modulate cell growth and apoptosis. This gene is regarded as a potential tumour suppressor gene.
Saturday, May 28, 2016
Mitochondrial energy imbalance and lipid peroxidation cause cell death in Friedreich’s ataxia
R Abeti, M H Parkinson, I P Hargreaves, P R Angelova, C Sandi, M A Pook, P Giunti and A Y Abramov. Cell Death and Disease (2016) 7, e2237; doi:10.1038/cddis.2016.111 Published online 26 May 2016
Open
Although the role of frataxin is largely known, being fundamental for the iron biogenesis in the cell, the relation between frataxin and mitochondrial bioenergetics is not completely clear.
We assessed the type of mitochondrial dysfunction that was present in the cerebellum, concluding that Complex I activity is impaired, but Complex II compensates by overworking. Therefore, if we consider the ETC, we can define the mitochondrial dysfunction as a mildly defective bioenergetic phenotype. However, this mild dysfunction drives the formation of free radicals that cannot be attenuated by the endogenous antioxidant systems, which are downregulated. Thus, the level of lipid peroxidation increases dramatically, damaging the cells and causing premature cell death. Therefore, lipid peroxidation could be a potential target for future therapeutic approaches in FRDA.
Open
Although the role of frataxin is largely known, being fundamental for the iron biogenesis in the cell, the relation between frataxin and mitochondrial bioenergetics is not completely clear.
We assessed the type of mitochondrial dysfunction that was present in the cerebellum, concluding that Complex I activity is impaired, but Complex II compensates by overworking. Therefore, if we consider the ETC, we can define the mitochondrial dysfunction as a mildly defective bioenergetic phenotype. However, this mild dysfunction drives the formation of free radicals that cannot be attenuated by the endogenous antioxidant systems, which are downregulated. Thus, the level of lipid peroxidation increases dramatically, damaging the cells and causing premature cell death. Therefore, lipid peroxidation could be a potential target for future therapeutic approaches in FRDA.
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