An exploratory qualitative investigation of psychosocial determinants of parental decisions to support sport participation for youth with a mobility impairment

Celina H. Shirazipour, Amy E. Latimer-Cheung, Kelly P. Arbour-Nicitopoulos, Research in Developmental Disabilities, Volumes 45–46, October–November 2015, Pages 400-410, ISSN 0891-4222, http://dx.doi.org/10.1016/j.ridd.2015.08.001.

Compared to parents of non-athletes, parents of athletes identified different, more specific positive outcome expectations, including: being included and family networking. First, while parents of non-athletes viewed inclusion as a social benefit, half of parents of athletes stated that inclusion through sport and being part of the mainstream were important benefits in their own rights, providing distinct outcomes including a sense of normalcy. Second, half of the parents of athletes identified the family benefit of networking with other families. The family network developed within the sport organization provided opportunities to share their enjoyment of their children’s participation, discuss impairment concerns, and gain knowledge from others’ experiences.

Evidence for chromosome fragility at the frataxin locus in Friedreich ataxia

Daman Kumari, Bruce Hayward, Asako J. Nakamura, William M. Bonner, Karen Usdin,Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Available online 30 August 2015, ISSN 0027-5107, http://dx.doi.org/10.1016/j.mrfmmm.2015.08.007.

The region of chromosome 9 that contains the Frataxin (FXN) locus is prone to breakage and rearrangements.This chromosome fragility involves the generation of chromosome/chromatid gaps or breaks, or the high frequency loss of one or both copies of the affected gene when cells are grown under folate stress or as we showed previously, in the presence of an inhibitor of the ATM checkpoint kinase.

Investigation of mitochondrial DNA variations among Indian Friedreich's ataxia (FRDA) patients

Inder Singh, Mohammed Faruq, Madakasira Vasantha Padma, Vinay Goyal, Madhuri Behari, Ashoo Grover, Mitali Mukerji, Achal K. Srivastava, Mitochondrion, Available online 29 August 2015, ISSN 1567-7249, http://dx.doi.org/10.1016/j.mito.2015.08.003.

Overall, our study identifies the functionally important variations and mitochondrial lineage of Indian FRDA cases and, that underscores the importance of studying the role of mitochondrial genome variations in FRDA.

Stable isotopes and LC–MS for monitoring metabolic disturbances in Friedreich's ataxia platelets

Andrew J Worth, Sankha S Basu, Eric C Deutsch, Wei-Ting Hwang, Nathaniel W Snyder, David R Lynch, and Ian A Blair, Bioanalysis, Vol. 7, No. 15 , Pages 1843-1855 (doi: 10.4155/bio.15.118)

Platelets can be used as a surrogate tissue for in vivo biomarker studies to monitor new therapeutic approaches for the treatment of FRDA.

MDA Awards $10 million in new Research Grants

CHICAGO, Aug. 26, 2015 /PRNewswire/ -- Powered by its big-picture perspective to accelerate treatments and cures across the broad spectrum of neuromuscular diseases, MDA today announced the award of $10 million in new research grants to the world's brightest scientists conducting leading-edge discovery for muscular dystrophy, ALS and related muscle-debilitating diseases.

Among the new MDA research grants: Expanding therapeutic possibilities in Friedreich's ataxia (FA): Scientists at the University of Oklahoma Health Sciences Center will work to find the optimal HDAC inhibitor and dose for increasing production of the frataxin protein, which is deficient in FA and, in parallel, test an alternative HDAC inhibitor that may prove more effective than others tested to date.

Riluzole in patients with hereditary cerebellar ataxia: a randomised, double-blind, placebo-controlled trial

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.

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.

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

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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. 

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.

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

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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.

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

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.

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.

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

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 .....

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.

Idebenone Protects against Oxidized Low Density Lipoprotein Induced Mitochondrial Dysfunction in Vascular Endothelial Cells via GSK3β/β-catenin signaling pathways

Pengfei Lin, Junling Liu, Ming Ren, Kunqian Ji, Ling Li, Bin Zhang, Yaoqin Gong, Chuanzhu Yan, Idebenone Protects against Oxidized Low Density Lipoprotein Induced Mitochondrial Dysfunction in Vascular Endothelial Cells via GSK3β/β-catenin signaling pathways, Biochemical and Biophysical Research Communications, Available online 15 August 2015, ISSN 0006-291X, http://dx.doi.org/10.1016/j.bbrc.2015.08.058.

Intel just open sourced Stephen Hawking’s speech system and it’s a .NET 4.5 WinForms app that you can try for yourself

Mansib Rahman, Canadian Developer Connection. 14 Aug 2015

As we all know, the venerable physicist Professor Stephen Hawking is unable to talk as he is afflicted with ALS and thus relies on a computer system to communicate. In 2011, his condition was deteriorating so badly that he could best communicate at a rate of only 2 words per minute. He reached out to Alan Moore at Intel and asked if Intel could come up with new technology to help his plight.

Well, what are you waiting for? You can try all this out for yourself. Visit the software's Github release page to get the installer.

Nrf2—a therapeutic target for the treatment of neurodegenerative diseases

Nrf2—a therapeutic target for the treatment of neurodegenerative diseases. Delinda A. Johnson, Jeffrey A. Johnson, Free Radical Biology and Medicine, Available online 14 August 2015, Page FRBMD1500535, ISSN 0891-5849, http://dx.doi.org/10.1016/j.freeradbiomed.2015.07.147.

The brain is very sensitive to changes in redox status; thus maintaining redox homeostasis in the brain is critical for the prevention of accumulating oxidative damage. Recently, a clinical trial using RTA 408 was initiated for Friedreich’s ataxia, a neurodegenerative condition responsible for cerebellar ataxia due to impaired production of the protein frataxin leading to profound deficiencies in mitochondrial respiration (ClinicalTrials.gov Identifier NCT02255435).

PATENT: SMALL MOLECULE ACTIVATORS OF MITOCHONDRIAL FUNCTION

NEW PATENT: SMALL MOLECULE ACTIVATORS OF MITOCHONDRIAL FUNCTION.
Inventor(s): WILSON ROBERT B [US]; COTTICELLI MARIA GRAZIA [US]; BENEDETTI PHILLIP A [US]; SMITH AMOS [US]; MELVIN JASON E [US]; HURYN DONNA M [US]
Applicant(s): UNIV PENNSYLVANIA [US]
Original document: WO2010068767 (A1) ― 2010-06-17

Key Patent Granted For AAVLife’s Gene-Therapy Program to Treat Cardiomyopathy in Friedreich’s Ataxia

Key Patent Granted For AAVLife’s Gene-Therapy Program to Treat Cardiomyopathy in Friedreich’s Ataxia. BUSINESS WIRE, August 05, 2015

The patent broadly protects a promising method for treating cardiomyopathy by using an adeno-associated virus (AAV) vector to carry into cells a gene expressing the protein frataxin. The patent will run until 2033 or longer in the event of a successful application for an extension. Corresponding patent applications are pending in major markets globally. 

The quality of economic evaluations of ultra-orphan drugs in Europe – a systematic review

The quality of economic evaluations of ultra-orphan drugs in Europe – a systematic review. Y. Schuller, C. E. M. Hollak and M. Biegstraaten; Orphanet Journal of Rare Diseases 2015, 10:92 doi:10.1186/s13023-015-0305-y

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In the European Union (EU), a disease is considered ‘orphan’ if it is a life-threatening or seriously debilitating disorder that affects fewer than 1 per 2 000. An orphan disease is defined in the EU as a disorder affecting less than 1 in 2 000 individuals. The concept of ultra-orphan has been proposed for diseases with a prevalence of less than 1:50 000. According to this classification Friedreich's Ataxia is within the group of the "orphan", although is close to the upper border of the "ultra-orphan", so share with the "ultra-orphan" many of the problems for the development of drugs and therapies.