C. Bui, R.B. Wilson, D.R. Lynch, J.W. Rossano, O. Elci, K.Y. Lin, The Journal of Heart and Lung Transplantation, Volume 35, Issue 4, Supplement, April 2016, Page S172, ISSN 1053-2498, doi:10.1016/j.healun.2016.01.479.
We hypothesized that serum markers of cardiac injury, stress, fibrosis, and inflammation are higher in FA subjects than non-FA controls, and these markers correlate with echocardiographic markers of cardiomyopathy.
Friday, April 22, 2016
Thursday, April 21, 2016
Abundance and Significance of Iron, Zinc, Copper, and Calcium in the Hearts of Patients with Friedreich Ataxia
Pamela C. Kruger, Karl X. Yang, Patrick J. Parsons, Alyssa B. Becker, Paul J. Feustel, Arnulf H. Koeppen. The American Journal of Cardiology, Available online 20 April 2016, ISSN 0002-9149, doi: 10.1016/j.amjcard.2016.04.024.
Total levels of Fe in bulk extracts were not significantly higher than normal, and the concentrations of Zn also remained in the normal range. Cu levels, however, were significantly lower in FA.
Total levels of Fe in bulk extracts were not significantly higher than normal, and the concentrations of Zn also remained in the normal range. Cu levels, however, were significantly lower in FA.
Wednesday, April 20, 2016
Idebenone in Friedreich ataxia and Leber’s hereditary optic neuropathy: close mechanisms, similar therapy?
Manuel Schiff, Pierre Rustin. Brain (2016) aww085 DOI: 10.1093/brain/aww085 First published online: 19 April 2016
"Yet despite these studies, there is no clear consensus on the benefits of idebenone therapy for patients with Friedreich ataxia. Nevertheless, being essentially harmless idebenone has been, and is still, given to many patients with Friedreich ataxia all over the world."
However, for legal and/or marketing reasons, recent idebenone authorization for LHON resulted in some patients with Friedreich ataxia having difficulty obtaining it.
So far the occurrence of potential responders to idebenone in Friedreich ataxia has not been rigorously examined, but in view of the data obtained in LHON, defining a subgroup of therapy-responder patients appears a reasonable objective for next trials in this (and other) rare disease.
"Yet despite these studies, there is no clear consensus on the benefits of idebenone therapy for patients with Friedreich ataxia. Nevertheless, being essentially harmless idebenone has been, and is still, given to many patients with Friedreich ataxia all over the world."
However, for legal and/or marketing reasons, recent idebenone authorization for LHON resulted in some patients with Friedreich ataxia having difficulty obtaining it.
So far the occurrence of potential responders to idebenone in Friedreich ataxia has not been rigorously examined, but in view of the data obtained in LHON, defining a subgroup of therapy-responder patients appears a reasonable objective for next trials in this (and other) rare disease.
Tuesday, April 19, 2016
Plasma circulating cell-free mitochondrial DNA in the assessment of Friedreich's ataxia
Subrahamanyam Dantham, Achal K. Srivastava, Sheffali Gulati, Moganty R. Rajeswari, Journal of the Neurological Sciences, Available online 14 April 2016, ISSN 0022-510X, doi:10.1016/j.jns.2016.04.016.
Despite several therapies under study or in development for FRDA, evaluation of therapeutic efficacy is limited by the lack of minimally invasive biomarkers to assess disease progression and severity.
Our study identified three major findings, 1. FRDA patients showed decrease in the levels of plasma mtDNA, whereas plasma nDNA was increased. 2. Plasma mtDNA has shown to exhibit high sensitivity and specificity in discriminating FRDA patients from the healthy controls over plasma nDNA levels 3. Significant serial changes have been observed in case of plasma mtDNA upon intervention with nutrient supplement (omega-3 fatty acids).
In view of their neuro-cardio protective role and positive effect on mitochondrial metabolism in ameliorating the neuro symptoms, the Omega-3 fatty acids (Eicosapentaenoic acid and docosahexaenoic acid) have been recommended as a nutritional supplement
Despite several therapies under study or in development for FRDA, evaluation of therapeutic efficacy is limited by the lack of minimally invasive biomarkers to assess disease progression and severity.
Our study identified three major findings, 1. FRDA patients showed decrease in the levels of plasma mtDNA, whereas plasma nDNA was increased. 2. Plasma mtDNA has shown to exhibit high sensitivity and specificity in discriminating FRDA patients from the healthy controls over plasma nDNA levels 3. Significant serial changes have been observed in case of plasma mtDNA upon intervention with nutrient supplement (omega-3 fatty acids).
In view of their neuro-cardio protective role and positive effect on mitochondrial metabolism in ameliorating the neuro symptoms, the Omega-3 fatty acids (Eicosapentaenoic acid and docosahexaenoic acid) have been recommended as a nutritional supplement
Monday, April 18, 2016
Two different pathogenic mechanisms, dying-back axonal neuropathy and pancreatic senescence, are present in the YG8R mouse model of Friedreich ataxia
Belén Mollá, Fátima Riveiro, Arantxa Bolinches-Amorós, Diana C. Muñoz-Lasso, Francesc Palau, Pilar González-Cabo. Disease Models and Mechanisms 2016 : doi: 10.1242/dmm.024273
OPEN ACCESS
These results confirm that the lack of frataxin induces different pathogenic mechanisms in nervous system and pancreas in the mouse model of FRDA: sensory nerve dying-back and pancreatic senescence.
OPEN ACCESS
These results confirm that the lack of frataxin induces different pathogenic mechanisms in nervous system and pancreas in the mouse model of FRDA: sensory nerve dying-back and pancreatic senescence.
Sunday, April 17, 2016
Original Research Proposal: Creation of an Iron Sensing FXN mRNA Therapeutic Riboswitch for the Treatment of Friedreich's Ataxia
Stephanie Mack, Das Research Group, Department of Chemistry, Carnegie Mellon University
Location: Mellon Institute Room 355
Location: Mellon Institute Room 355
Development of an AAV9 coding for a 3XFLAG-TALEfrat#8-VP64 able to increase in vivo the human frataxin in YG8R mice
P Chapdelaine, C Gérard, N Sanchez, K Cherif, J Rousseau, D L Ouellet, D Jauvin and J P Tremblay. Gene Ther. accepted article preview 2016 Apr 15. doi: 10.1038/gt.2016.36.
OPEN
The study indicates that an AAV coding for a TALE protein coupled with a TAD may be used to increase gene expression in vivo as a possible treatment not only for FRDA but also for other haploinsufficiency diseases.
OPEN
The study indicates that an AAV coding for a TALE protein coupled with a TAD may be used to increase gene expression in vivo as a possible treatment not only for FRDA but also for other haploinsufficiency diseases.
Saturday, April 16, 2016
Lymphoblast Oxidative Stress Genes as Potential Biomarkers of Disease Severity and Drug Effect in Friedreich's Ataxia
Hayashi G, Cortopassi G. PLoS ONE 11(4): e0153574. doi:10.1371/journal.pone.0153574
OPEN ACCESS
This work demonstrates that the mRNA abundance of the oxidative stress response genes NCF2 and PDLIM1 are potential biomarkers for FA. Additionally, because NCF2 and PDLIM1 respond dose-dependently to frataxin level, they supplement and confirm the antioxidant effects of therapies that raise frataxin, increasing the number of Friedreich's relevant biomarkers to three in the lymphoblast context: frataxin, NCF2, and PDLIM1. Lastly, because PDLIM1/CLP36 has recently been shown to be responsive to Nrf2 status/oxidative stress in cardiomyocytes, it could become a valuable marker of drug effect in cardiomyocytes.
OPEN ACCESS
This work demonstrates that the mRNA abundance of the oxidative stress response genes NCF2 and PDLIM1 are potential biomarkers for FA. Additionally, because NCF2 and PDLIM1 respond dose-dependently to frataxin level, they supplement and confirm the antioxidant effects of therapies that raise frataxin, increasing the number of Friedreich's relevant biomarkers to three in the lymphoblast context: frataxin, NCF2, and PDLIM1. Lastly, because PDLIM1/CLP36 has recently been shown to be responsive to Nrf2 status/oxidative stress in cardiomyocytes, it could become a valuable marker of drug effect in cardiomyocytes.
Friday, April 15, 2016
Comorbid Medical Conditions in Friedreich Ataxia: Association With Inflammatory Bowel Disease and Growth Hormone Deficiency
Julianna E. Shinnick, Kimberly Schadt, Cassandra Strawser, Nicholas Wilcox, Susan L. Perlman, George R. Wilmot, Christopher M. Gomez, Katherine D. Mathews, Grace Yoon, Theresa Zesiewicz, Chad Hoyle, S. H. Subramony, Eppie M. Yiu, Martin B. Delatycki, Alicia F. Brocht, Jennifer M. Farmer, and David R. Lynch; J Child Neurol 0883073816643408, first published on April 12, 2016 as doi:10.1177/0883073816643408
Diagnoses with more than twice the prevalence in this Friedreich ataxia cohort than the general population were growth hormone deficiency, ulcerative colitis, Crohn’s disease, and inflammatory bowel disease. However, patients with Friedreich ataxia did not have a higher incidence of other neurological disorders such as epilepsy or migraine; other sleep disorders besides sleep apnea; other cardiovascular disorders such as coronary artery disease, hypercholesterolemia, or hypertension; or psychiatric disorders such as anxiety
Diagnoses with more than twice the prevalence in this Friedreich ataxia cohort than the general population were growth hormone deficiency, ulcerative colitis, Crohn’s disease, and inflammatory bowel disease. However, patients with Friedreich ataxia did not have a higher incidence of other neurological disorders such as epilepsy or migraine; other sleep disorders besides sleep apnea; other cardiovascular disorders such as coronary artery disease, hypercholesterolemia, or hypertension; or psychiatric disorders such as anxiety
Thursday, April 14, 2016
Researchers from Mount Sinai and Sage Bionetworks Report Analysis of Nearly 600,000 Genomes for Resilience Project
Icahn School of Medicine at Mount Sinai, New York, NY – April 11, 2016 /Press Release/ ––
As part of a global collaboration, scientists from the Icahn School of Medicine at Mount Sinai and Sage Bionetworks conducted the largest genome study to date and reported the first systematic search across hundreds of Mendelian disorders in hundreds of thousands of individuals apparently not afflicted with any of these disorders to identify those carrying disease protective factors. Genome analysis of these resilient people could uncover naturally occurring, protective mechanisms that would serve as novel treatments for people affected by these diseases.
In this study, researchers analyzed DNA from 12 previously collected data sets, using a newly developed targeted sequencing panel to screen 874 genes for 584 distinct genetic diseases. The diseases, which were mostly metabolic conditions, neurological diseases, or developmental disorders, present in childhood with severe symptoms. All genomes analyzed were from adults who had never been diagnosed with any of these diseases. A sophisticated, in-depth analysis process identified 13 healthy people with genetic variants associated with eight diseases.
As part of a global collaboration, scientists from the Icahn School of Medicine at Mount Sinai and Sage Bionetworks conducted the largest genome study to date and reported the first systematic search across hundreds of Mendelian disorders in hundreds of thousands of individuals apparently not afflicted with any of these disorders to identify those carrying disease protective factors. Genome analysis of these resilient people could uncover naturally occurring, protective mechanisms that would serve as novel treatments for people affected by these diseases.
In this study, researchers analyzed DNA from 12 previously collected data sets, using a newly developed targeted sequencing panel to screen 874 genes for 584 distinct genetic diseases. The diseases, which were mostly metabolic conditions, neurological diseases, or developmental disorders, present in childhood with severe symptoms. All genomes analyzed were from adults who had never been diagnosed with any of these diseases. A sophisticated, in-depth analysis process identified 13 healthy people with genetic variants associated with eight diseases.
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