Caron, Elena MD; Burns, Dennis MD; Castro, Diana MD; Iannaccone, Susan T. MD, Journal of Clinical Neuromuscular Disease:
September 2015 - Volume 17 - Issue 1 - p 13–17, doi: 10.1097/CND.0000000000000086
Missense mutations are rare causes of Friedreich ataxia that can only be detected by sequencing of the FXN gene. Sequencing of the FXN gene is essential to make an early diagnosis when there is an atypical phenotype.
Tuesday, August 25, 2015
Sunday, August 23, 2015
Effectiveness, safety and costs of orphan drugs: an evidence-based review
Effectiveness, safety and costs of orphan drugs: an evidence-based review Evidence based practice . Igho J Onakpoya, Elizabeth A Spencer, Matthew J Thompson, Carl J Heneghan; BMJ Open 2015;5:e007199 doi:10.1136/bmjopen-2014-007199
OPEN ACCESS
The available evidence suggests that there is inconsistency in the quality of evidence of approved orphan drugs, and there is no clear mechanism for determining their prices. In some cases, far cheaper generic agents appear to be available. A more robust, transparent and standard mechanism for determining annual costs is imperative
OPEN ACCESS
The available evidence suggests that there is inconsistency in the quality of evidence of approved orphan drugs, and there is no clear mechanism for determining their prices. In some cases, far cheaper generic agents appear to be available. A more robust, transparent and standard mechanism for determining annual costs is imperative
Targeting mitochondrial metal dyshomeostasis for the treatment of neurodegeneration
Jeffrey R Liddell, Neurodegenerative Disease Management, Posted online on August 21, 2015. (doi:10.2217/nmt.15.19)
Several trials indicate that redistributing iron may be an effective treatment for FRDA, but precise dosage control is required for optimal results.
Several trials indicate that redistributing iron may be an effective treatment for FRDA, but precise dosage control is required for optimal results.
Friday, August 21, 2015
Phenotypic Screening for Friedreich Ataxia Using Random shRNA Selection
M. Grazia Cotticelli, Fabio Acquaviva, Shujuan Xia, Avinash Kaur, Yongping Wang, Robert B. Wilson; J Biomol Screen August 18, 2015, doi: 10.1177/1087057115600433
Wednesday, August 19, 2015
The EuroBioBank Network: 10 years of hands-on experience of collaborative, transnational biobanking for rare diseases
Marina Mora, Corrado Angelini, Fabrizia Bignami, Anne-Mary Bodin, Marco Crimi, Jeanne- Hélène Di Donato, Alex Felice, Cécile Jaeger, Veronika Karcagi, Yann LeCam, Stephen Lynn, Marija Meznaric, Maurizio Moggio, Lucia Monaco, Luisa Politano, Manuel Posada de la Paz, Safaa Saker, Peter Schneiderat, Monica Ensini, Barbara Garavaglia, David Gurwitz, Diana Johnson, Francesco Muntoni, Jack Puymirat, Mojgan Reza, Thomas Voit, Chiara Baldo, Franca Dagna Bricarelli, Stefano Goldwurm, Giuseppe Merla, Elena Pegoraro, Alessandra Renieri, Kurt Zatlouka, Mirella Filocamo and Hanns Lochmüller; European Journal of Human Genetics (2015) 23, 1116–1123; doi:10.1038/ejhg.2014.272;
In the field of rare diseases (RDs) the number of available biospecimens is, in general, very limited. As a direct consequence of disease rarity, clinical trials are difficult to perform and so a limited number of treatments have been developed, whereas disease prognosis and natural history are poorly known, and patients with RDs do not receive the care and medical attention available to people with common diseases. Sharing material and data on RDs is essential for identifying disease-causing genes, studying pathological mechanisms, and developing treatments.
In the field of rare diseases (RDs) the number of available biospecimens is, in general, very limited. As a direct consequence of disease rarity, clinical trials are difficult to perform and so a limited number of treatments have been developed, whereas disease prognosis and natural history are poorly known, and patients with RDs do not receive the care and medical attention available to people with common diseases. Sharing material and data on RDs is essential for identifying disease-causing genes, studying pathological mechanisms, and developing treatments.
Mitochondrial dynamism and heart disease: changing shape and shaping change
Gerald W Dorn; EMBO Mol Med. 2015 July; 7(7): 865–877. doi: 10.15252/emmm.201404575
A example of heart disease provoked by primary genetic mitochondrial dysfunction is Friedreich's ataxia. This autosomal recessive neurodegenerative disease is caused by triplet nucleotide repeat expansions within the FXN gene, encoding the mitochondrial matrix iron chaperone protein frataxin. In addition to progressive dorsal sensory nerve degeneration and ataxia, hypertrophic cardiomyopathy is seen in a majority of patients; heart failure is the terminal diagnosis in approximately one-third of affected individuals. Cardiac mitochondria in Friedreich's ataxia undergo massive proliferation with decreased ATP production, consistent with functional compromise of the electron transport chain.
A example of heart disease provoked by primary genetic mitochondrial dysfunction is Friedreich's ataxia. This autosomal recessive neurodegenerative disease is caused by triplet nucleotide repeat expansions within the FXN gene, encoding the mitochondrial matrix iron chaperone protein frataxin. In addition to progressive dorsal sensory nerve degeneration and ataxia, hypertrophic cardiomyopathy is seen in a majority of patients; heart failure is the terminal diagnosis in approximately one-third of affected individuals. Cardiac mitochondria in Friedreich's ataxia undergo massive proliferation with decreased ATP production, consistent with functional compromise of the electron transport chain.
Tuesday, August 18, 2015
PGC-1 coactivators in β-cells regulate lipid metabolism and are essential for insulin secretion coupled to fatty acids
Daniel Oropeza, Nathalie Jouvet, Khalil Bouyakdan, Gabrielle Perron, Lea-Jeanne Ringuette, Louis H. Philipson, Robert S. Kiss, Vincent Poitout, Thierry Alquier, Jennifer L. Estall, Molecular Metabolism, Available online 14 August 2015, ISSN 2212-8778, http://dx.doi.org/10.1016/j.molmet.2015.08.001.
"These data highlight the importance of PGC-1s in coupling β-cell lipid metabolism to promote efficient insulin secretion."
PGC-1alpha Down-Regulation has been previously described as an important factor involved in many aspects of the pathogenesis of Friedreich's ataxia. Dr. Massimo Pandolfo (*) in a paper published in 2010 linked it to the deficiencies in the antioxidant response in Friedreich's ataxia.
It is widely known his involvement in many mitochondrial diseases, neurodegenerative diseases, diabetes, heart disease, etc.
Even though is not a specific AF study, this article is particularly interesting because it increases the knowledge about the effects of PGC-1 variations in very important aspects presents in FA, mitochondrial disturbances, diabetes, altered lipid metabolism, etc.
Currently FA researchers are showing that exists also an important component due to altered lipid metabolism in the disease, accumulation of lipid droplets in some cell types most affected by the low level of frataxin could cause problems with the lipid oxidation increasing the oxidative stress.
*PGC-1alpha Down-Regulation Affects the Antioxidant Response in Friedreich's ataxia, PLoS ONE 5 (4): e10025 do:. 10.1371 / journal. pone. 0010025
"These data highlight the importance of PGC-1s in coupling β-cell lipid metabolism to promote efficient insulin secretion."
PGC-1alpha Down-Regulation has been previously described as an important factor involved in many aspects of the pathogenesis of Friedreich's ataxia. Dr. Massimo Pandolfo (*) in a paper published in 2010 linked it to the deficiencies in the antioxidant response in Friedreich's ataxia.
It is widely known his involvement in many mitochondrial diseases, neurodegenerative diseases, diabetes, heart disease, etc.
Even though is not a specific AF study, this article is particularly interesting because it increases the knowledge about the effects of PGC-1 variations in very important aspects presents in FA, mitochondrial disturbances, diabetes, altered lipid metabolism, etc.
Currently FA researchers are showing that exists also an important component due to altered lipid metabolism in the disease, accumulation of lipid droplets in some cell types most affected by the low level of frataxin could cause problems with the lipid oxidation increasing the oxidative stress.
*PGC-1alpha Down-Regulation Affects the Antioxidant Response in Friedreich's ataxia, PLoS ONE 5 (4): e10025 do:. 10.1371 / journal. pone. 0010025
Retrotope announces open enrollment for Friedreich's ataxia clinical trial
LOS ALTOS, Calif., Aug. 17, 2015 /PRNewswire/ -- Retrotope announces the opening of enrollment for a 28-day, first-in-human, randomized, double-blind, controlled, ascending dose study of orally dosed RT001 to evaluate the safety, tolerability, pharmacokinetics (PK), disease state, and exploratory endpoints in patients with Friedreich's ataxia (FA).
About RT001: Retrotope has discovered that a mechanism common to many degenerative diseases, namely, the free radical degradation of lipids in mitochondrial and cellular membranes, may actually cause disease. Free radicals attack and degrade the polyunsaturated fats (PUFAs) that are essential components of cellular membranes. We and others have shown that the degradation products of these fats are associated with many diseases of neurodegeneration and aging, and create further damage cascades that are toxic to cells. Retrotope's lead compound (RT001) is a patented, orally available, stabilized fatty-acid that shuts down this degradation and stabilizes ("fireproofs") cellular membranes against further attack.
The case of a missing QRS complex
Eric A. Meyerowitz, Ralph J. Verdino, The case of a missing QRS complex, Journal of Electrocardiology, Available online 8 August 2015, ISSN 0022-0736, http://dx.doi.org/10.1016/j.jelectrocard.2015.07.017.
A 26-year-old man with a history of Friedreich's ataxia, previously on no cardiac medications, presented to an outside hospital with new-onset systolic heart failure with an episode of chest pain and palpitations .....
A 26-year-old man with a history of Friedreich's ataxia, previously on no cardiac medications, presented to an outside hospital with new-onset systolic heart failure with an episode of chest pain and palpitations .....
Benefits of exercise in neurodegenerative diseases
By a lot of personal experiences explained by many affected by Friedreich's ataxia it is well known that exercise is beneficial to maintain the physical and psychological capabilities. These studies, in MS and in the early stages of Alzheimer's disease (AD), are pointing in the same direction in other neurodegenerative diseases.
Exercise May Reduce Disease Activity in Children With Multiple Sclerosis: DG News-Neurology, MINNEAPOLIS -- August 12, 2015 -- A study published in the online issue of the journal Neurology suggests children with multiple sclerosis (MS) who exercise regularly may have a less active disease.
“These findings add to the possibility that physical activity may have a beneficial effect on the health of the brain,” said Dr. Yeh. She noted that the study does not determine a cause-and-effect relationship between physical activity and disease activity in MS, but only shows an association between the two.
MRI Findings Show Neuroprotective Benefits of Aerobic Exercise in Patients With Early Alzheimer’s Disease: DocGuide Washington, DC -- July 22, 2015, by Brian Hoyle -- Aerobic exercise demonstrates neuroprotective benefits in the white matter connections of patients with early-stage Alzheimer’s disease (AD), according to results of a small, randomised study presented at the 2015 Alzheimer’s Association International Conference (AAIC).
Adherence to the exercise program was considered good in both the aerobic and nonaerobic groups (86.3% and 96.7%, respectively). These findings offer evidence-based support for the neuroprotective value of aerobic exercise. In particular, the researchers concluded, this patient population demonstrates that beneficial brain changes can occur even after the diagnosis of AD. The exercise was not overly taxing, Dr. Perea noted, and could be performed by many patients with AD, who would enjoy the other attendant benefits that exercise brings.
Exercise May Reduce Disease Activity in Children With Multiple Sclerosis: DG News-Neurology, MINNEAPOLIS -- August 12, 2015 -- A study published in the online issue of the journal Neurology suggests children with multiple sclerosis (MS) who exercise regularly may have a less active disease.
“These findings add to the possibility that physical activity may have a beneficial effect on the health of the brain,” said Dr. Yeh. She noted that the study does not determine a cause-and-effect relationship between physical activity and disease activity in MS, but only shows an association between the two.
MRI Findings Show Neuroprotective Benefits of Aerobic Exercise in Patients With Early Alzheimer’s Disease: DocGuide Washington, DC -- July 22, 2015, by Brian Hoyle -- Aerobic exercise demonstrates neuroprotective benefits in the white matter connections of patients with early-stage Alzheimer’s disease (AD), according to results of a small, randomised study presented at the 2015 Alzheimer’s Association International Conference (AAIC).
Adherence to the exercise program was considered good in both the aerobic and nonaerobic groups (86.3% and 96.7%, respectively). These findings offer evidence-based support for the neuroprotective value of aerobic exercise. In particular, the researchers concluded, this patient population demonstrates that beneficial brain changes can occur even after the diagnosis of AD. The exercise was not overly taxing, Dr. Perea noted, and could be performed by many patients with AD, who would enjoy the other attendant benefits that exercise brings.
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