Silvia Romano, Giulia Coarelli, Christian Marcotulli, Luca Leonardi, Francesca Piccolo, Maria Spadaro, Marina Frontali, Michela Ferraldeschi, Maria Chiara Vulpiani, Federica Ponzelli, Marco Salvetti, Francesco Orzi, Antonio Petrucci, Nicola Vanacore, Carlo Casali, Giovanni Ristori, The Lancet Neurology, Available online 25 August 2015, ISSN 1474-4422, http://dx.doi.org/10.1016/S1474-4422(15)00201-X.
Previous study in patients with cerebellar ataxias of different causes showed significant benefit of riluzole after 8 weeks. The study aimed to confirm these results in patients with spinocerebellar ataxia or Friedreich's ataxia in a 1-year trial.
This trial lends support to the idea that riluzole might be efficacious in the treatment of patients with cerebellar ataxia, in addition to its present indication for amyotrophic lateral sclerosis. The drug effect seems to be unaffected by adjustment for the different clinical forms of ataxia. The findings suggest that riluzole could eventually be used in clinical practice, but confirmatory studies on larger and disease-specific populations, for a longer observation period are needed.
Wednesday, August 26, 2015
Rare inherited diseases merit disease-specific trials
Alexandra Durr, The Lancet Neurology, Available online 25 August 2015, ISSN 1474-4422, http://dx.doi.org/10.1016/S1474-4422(15)00217-3.
Have Been recently presented the results the trial of riluzole, the study included patients with Friedreich's ataxia, SCA1, SCA2, SCA6, SCA8 and SCA10. Cerebellar ataxia, which include a multitude of different, rare genetic entities, are a difficult set of diseases for such studies.
The clinician eager to treat patients is left with some important questions about the design of trials for rare diseases. Is it appropriate to mix different forms of ataxias in a therapeutic trial?
To take into account the large variety of known and unknown confounding factors in disease progression and treatment response, trials in rare inherited diseases should: be disease-specific, and account for genetic forms of disease.
Have Been recently presented the results the trial of riluzole, the study included patients with Friedreich's ataxia, SCA1, SCA2, SCA6, SCA8 and SCA10. Cerebellar ataxia, which include a multitude of different, rare genetic entities, are a difficult set of diseases for such studies.
The clinician eager to treat patients is left with some important questions about the design of trials for rare diseases. Is it appropriate to mix different forms of ataxias in a therapeutic trial?
To take into account the large variety of known and unknown confounding factors in disease progression and treatment response, trials in rare inherited diseases should: be disease-specific, and account for genetic forms of disease.
Compassionate use of orphan drugs
Hanna I. Hyry, Jeremy Manuel, Timothy M. Cox and Jonathan C. P. Roos. Orphanet Journal of Rare Diseases 2015, 10:100 doi:10.1186/s13023-015-0306-x
OPEN ACCESS
Compelling self-interested, legal and ethical arguments can be mounted to encourage manufacturers to offer therapies on a compassionate use basis and these are often equally applicable to provision on a humanitarian aid basis. The EU’s compassionate use programmes are instrumental in ensuring continuity of access to drugs until approval and reimbursement decisions are finalised. We propose the creation of a registry of drugs offered on a compassionate use basis; further transparency would allow such programmes to be evaluated and direct patients to sources of treatment.
OPEN ACCESS
Compelling self-interested, legal and ethical arguments can be mounted to encourage manufacturers to offer therapies on a compassionate use basis and these are often equally applicable to provision on a humanitarian aid basis. The EU’s compassionate use programmes are instrumental in ensuring continuity of access to drugs until approval and reimbursement decisions are finalised. We propose the creation of a registry of drugs offered on a compassionate use basis; further transparency would allow such programmes to be evaluated and direct patients to sources of treatment.
Tuesday, August 25, 2015
Atypical Presentation for Friedreich Ataxia in a Child
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.
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.
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
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