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  • friederich ataxia question

    friederich ataxia question,
    today a lady from romania asked me if i can provide her some info regarding friederich ataxia [cure]..she is desperate to find a cure.any info guys?
    thank you .

  • #2
    Friedreich's ataxia is an autosomal recessive neurodegenerative disease that usually manifests initially in clumsy and awkward gait called ataxia. The gene responsible is has been localized to chromosome 9 and is due to GAA or triplet repeats in a protein called frataxin. Frataxin is localized in mitchondria and its deficit appears to cause oxidative stress and buildup of iron and free radicals in the cell's mitochondria. Other symptoms include loss of deep tendon reflexes and sensations in the extremities, dysarthria, as well as diabetes, cardiomyopathy, scoliosis, and foot deformities . The symptoms are due to degeneration of certain spinal tracts, particularly cerebellospinal tracts. Symptoms usually appear from 5-15 years but can appear as late as 50 years. It affects about 1:50,000 people in the USA. source)

    There is no cure for the condition even though they know the gene. Like the ALS gene, the deficit of this gene causes accumulation of free radicals. So, several clinical studies have tried treating patients with anti-oxidants, including coenzyme Q10, vitamin E, and idebenone. These may provide some limited benefits and particularly quinone therapy (Cooper & Schapira, 2007). There is a clinical trial in France aimed at reducing the iron accumulation in the mitochondria (Whitnall & Richardson, 2006).

    Like many neurodegenerative diseases, Freidreich ataxia sufferers have been the target of providers of stem cell therapies. So, for example, Angie McDonald went to Netherlands to receive umbilical cord blood transplants (Source). It is not clear that these so-called stem herapies will have any effects of Freidreich's ataxia because they probably do not do any chemoablation of the bone marrow and the cells are unlikely to engraft or last long in the body.

    One of the most promising advances came in 2006 when a group of researchers at Scripps Institute found that a class of enzymes called histone deacetylases will reactivate the silenced frataxin gene (Source). It should be noted that these studies were only done in tissue culture and not yet in people. Boesch, et al. (2007), that erythropietin increases frataxin levels in people with Friedreich's ataxia.

    Future therapies include gene therapy. For example, the frataxin gene has been successfully transferred to mice to treat Freidreich's ataxia in mice (Lim, et al., 2007).

    • Whitnall M and Richardson DR (2006). Iron: a new target for pharmacological intervention in neurodegenerative diseases. Semin Pediatr Neurol. 13: 186-97. Iron Metabolism and Chelation Program, Department of Pathology, University of Sydney, Sydney, New South Wales, Australia. Iron (Fe) is an essential element that is imperative for the redox-driven processes of oxygen transport, electron transport, and DNA synthesis. However, in the absence of appropriate storage or chelation, excess-free Fe readily participates in the formation of toxic-free radicals, inducing oxidative stress and apoptosis. A growing body of evidence suggests that Fe may play some role in neurodegenerative diseases such as Huntington disease, Alzheimer's disease, Parkinson's disease, and particularly Friedreich's ataxia. This review examines the role of Fe in the pathology of these conditions and the potential use of Fe chelators as therapeutic agents for the treatment of neurodegenerative disorders. Consideration is given to the features that comprise a clinically successful Fe chelator, with focus on the development of ligands such as desferrioxamine, clioquinol, pyridoxal isonicotinoyl hydrazone, and other novel aroylhydrazones.
    • Cooper JM and Schapira AH (2007). Friedreich's ataxia: coenzyme Q10 and vitamin E therapy. Mitochondrion. 7 Suppl: S127-35. University Department of Clinical Neurosciences, Royal Free and University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK. Since the identification of the genetic mutation causing Friedreich's ataxia (FRDA) our understanding of the mechanisms underlying disease pathogenesis have improved markedly. The genetic abnormality results in the deficiency of frataxin, a protein targeted to the mitochondrion. There is extensive evidence that mitochondrial respiratory chain dysfunction, oxidative damage and iron accumulation play significant roles in the disease mechanism. There remains considerable debate as to the normal function of frataxin, but it is likely to be involved in mitochondrial iron handling, antioxidant regulation, and/or iron sulphur centre regulation. Therapeutic avenues for patients with FRDA are beginning to be explored in particular targeting antioxidant protection, enhancement of mitochondrial oxidative phosphorylation, iron chelation and more recently increasing FRDA transcription. The use of quinone therapy has been the most extensively studied to date with clear benefits demonstrated using evaluations of both disease biomarkers and clinical symptoms, and this is the topic that will be covered in this review.
    • Boesch S, Sturm B, Hering S, Goldenberg H, Poewe W and Scheiber-Mojdehkar B (2007). Friedreich's ataxia: clinical pilot trial with recombinant human erythropoietin. Ann Neurol. 62: 521-4. Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. To determine the role of recombinant human erythropoietin as a possible treatment option in Friedreich's ataxia, we performed an open-label clinical pilot study. Primary outcome measure was the change of frataxin levels at week 8 versus baseline. Twelve Friedreich's ataxia patients received 5,000 units recombinant human erythropoietin three times weekly subcutaneously. Frataxin levels were measured in isolated lymphocytes by enzyme-linked immunosorbent assay. In addition, urinary 8-hydroxydeoxyguanosine and serum peroxides, were measured. Treatment with recombinant human erythropoietin showed a persistent and significant increase in frataxin levels after 8 weeks (p < 0.01). All patients showed a reduction of oxidative stress markers.
    • Lim F, Palomo GM, Mauritz C, Gimenez-Cassina A, Illana B, Wandosell F and Diaz-Nido J (2007). Functional recovery in a Friedreich's ataxia mouse model by frataxin gene transfer using an HSV-1 amplicon vector. Mol Ther. 15: 1072-8. Departamento de Biologia Molecular, Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Universidad Autonoma de, Madrid, Madrid, Spain. There is currently no effective treatment for Friedreich's ataxia (FA), the most common of the hereditary ataxias. The disease is caused by mutations in FRDA that drastically reduce expression levels of the mitochondrial protein frataxin. In FA animal models, a key difficulty is obtaining the precise levels of frataxin expression in the appropriate tissues to provoke pathology without early lethality. To develop strategies to circumvent these problems, conditional frataxin transgenic mice have been generated. We now show that frataxin expression can be eliminated in neurons from these loxP[frda] mice by infection with CRE-expressing herpes simplex virus type 1 (HSV-1) amplicon vectors. We have also achieved in vivo delivery by stereotaxic injection of these CRE-expressing vectors into the brainstem of loxP[frda] mice to generate a localized gene knockout model. These mice develop a behavioral deficit in the rotarod assay detectable after 4 weeks, and when re-injected with HSV-1 amplicon vectors expressing human frataxin complementary DNA (cDNA) exhibit behavioral recovery as early as 4 weeks after the second injection. To the best of our knowledge, this is the first proof of principle of recovery of neurological function by a therapeutic agent aimed at correcting frataxin deficiency.
    • Gomez-Sebastian S, Gimenez-Cassina A, Diaz-Nido J, Lim F and Wade-Martins R (2007). Infectious delivery and expression of a 135 kb human FRDA genomic DNA locus complements Friedreich's ataxia deficiency in human cells. Mol Ther. 15: 248-54. The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. Friedreich's ataxia (FA) is the most common recessive ataxia, affecting 1-2 in 50,000 Caucasians, and there is currently no effective cure or treatment. FA results from a deficiency of the mitochondrial protein frataxin brought about by a repeat expansion in intron 1 of the FRDA gene. The main areas affected are the central nervous system (particularly the spinocerebellar system) and cardiac tissue. Therapies aimed at alleviating the neurological degeneration have proved unsuccessful to date. Here, we describe the construction and delivery of high capacity herpes simplex virus type 1 (HSV-1) amplicon vectors expressing the entire 80 kb FRDA genomic locus, driven by the endogenous FRDA promoter and including all introns and flanking regulatory sequences within a 135 kb genomic DNA insert. FA patient primary fibroblasts deficient in frataxin protein and exhibiting sensitivity to oxidative stress were transduced at high efficiency by FRDA genomic locus vectors. Following vector transduction, expression of FRDA protein by immunofluorescence was shown. Finally, functional complementation studies demonstrated restoration of the wild-type cellular phenotype in response to oxidative stress in transduced FA patient cells. These results suggest the potential of the infectious bacterial artificial chromosome-FRDA vectors for gene therapy of FA.


    • #3
      Originally posted by adi chicago
      friederich ataxia question,
      today a lady from romania asked me if i can provide her some info regarding friederich ataxia [cure]..she is desperate to find a cure.any info guys?
      thank you .
      Google it. It is written friedrich ataxia and I am sure you can find some information in your language, I found information in Norwegian at least
      TH 12, 43 years post


      • #4
        thank you very much for the info. dr.young.


        • #5
          Originally posted by woman from Europe
          Google it. It is written friedrich ataxia and I am sure you can find some information in your language, I found information in Norwegian at least
          The spelling of the disease name is "Friedreich's ataxia", "ie" before "ei". However, I was amazed how commonly the word is mispelled by medical web sites (i.e. Source).

          So, google for "Friedreich's".


          • #6
            Friedreich's Ataxis (FA) is considered by the Muscular Dystrophy Association and researchers to be under the muscular dystorphies order of diseases. The following link gives a contact address and phone number for information in Romania:


            While the main topic of this site is Prader Willi Syndrome that effects mental development and weight problems associated with an associated endocrine disorder it also gives information on the Romanian Organization on Rare Disorders. Adi, you and your friend may wish to join this group. They advocate for research, medical care and inclusion in the community. Welcome to the world of being a self-advocate, Adi.


            A list of organizations in Romania helping the disabled medically, socially and educationally.

            Courage doesn't always roar. Sometimes courage is the quiet voice at the end of the day saying, "I will try again tomorrow."

            Disclaimer: Answers, suggestions, and/or comments do not constitute medical advice expressed or implied and are based solely on my experiences as a SCI patient. Please consult your attending physician for medical advise and treatment. In the event of a medical emergency please call 911.


            • #7
              Thank you very much for the info Sue .