Anne Laure Simon, Jean Meyblum, Bastien Roche, Christophe Vidal, Keyvan Mazda, Isabelle Husson, Brice Ilharrebord; Spine Deformity,
Volume 7, Issue 5, 2019, Pages 812-821, doi:10.1016/j.jspd.2019.02.005.
The prevalence of scoliosis in FA was high (71%), and thoracic hyperkyphosis, with anterior misalignment, was frequently observed, which might be related to the anterior imbalance frequently encountered in patients with an ataxia. Posterior fusion including sacral instrumentation was only performed in nonambulatory patients, and the loss of ambulation was not associated with spinal surgery.
Sunday, September 8, 2019
Friday, September 6, 2019
Biohackers are pirating a cheap version of a million-dollar gene therapy
MIT Technology Review magazine, Aug 30, 2019. by Alex Pearlman
A group of independent biologists say they plan to copy a costly gene therapy. Are they medicine’s Robin Hood or a threat to safety?
The drug being copied is Glybera, a gene therapy that was the world’s most expensive drug when it came on the market in Europe in 2015 with a price tag of $1 million per treatment. Glybera was the first gene therapy ever approved to treat an inherited disease.
The gene therapy that the biohackers say they are copying, Glybera, was approved for people with an ultra-rare blood disease called lipoprotein lipase deficiency. But it didn’t prove cost-effective and was pulled from the market in 2017 by its manufacturer, UniQure. To date, only one insurer, in Germany, is known to have paid for the treatment.
“This was developed in a shed in Mississippi, a warehouse in Florida, a bedroom in Indiana, and on a computer in Austria,” says Gabriel Licina, a biohacker based in South Bend, Indiana. He says the prototype gene therapy cost less than $7,000 to create.
This year the Swiss pharmaceutical firm Novartis introduced another gene therapy, Zolgesma, for spinal muscular atrophy, with a price of $2.1 million. Because of the cost, some parents have struggled to obtain it for their children and the treatment is unlikely to be made available in most of the world.
“It’s a fairly big deal to see biohackers turning their focus to gene therapies because the potential consequences can be quite large,” said Rachel Sachs, an associate professor of law at Washington University in St. Louis and an expert on drug pricing. “They may see themselves as serving the interests of the patient community.”
A group of independent biologists say they plan to copy a costly gene therapy. Are they medicine’s Robin Hood or a threat to safety?
The drug being copied is Glybera, a gene therapy that was the world’s most expensive drug when it came on the market in Europe in 2015 with a price tag of $1 million per treatment. Glybera was the first gene therapy ever approved to treat an inherited disease.
The gene therapy that the biohackers say they are copying, Glybera, was approved for people with an ultra-rare blood disease called lipoprotein lipase deficiency. But it didn’t prove cost-effective and was pulled from the market in 2017 by its manufacturer, UniQure. To date, only one insurer, in Germany, is known to have paid for the treatment.
“This was developed in a shed in Mississippi, a warehouse in Florida, a bedroom in Indiana, and on a computer in Austria,” says Gabriel Licina, a biohacker based in South Bend, Indiana. He says the prototype gene therapy cost less than $7,000 to create.
This year the Swiss pharmaceutical firm Novartis introduced another gene therapy, Zolgesma, for spinal muscular atrophy, with a price of $2.1 million. Because of the cost, some parents have struggled to obtain it for their children and the treatment is unlikely to be made available in most of the world.
“It’s a fairly big deal to see biohackers turning their focus to gene therapies because the potential consequences can be quite large,” said Rachel Sachs, an associate professor of law at Washington University in St. Louis and an expert on drug pricing. “They may see themselves as serving the interests of the patient community.”
Thursday, September 5, 2019
Newly Funded FARA Grants, July 2019
Newly Funded FARA Grants, July 2019
FARA's most recent grant round was of very high quality, and included some very innovative research. After much work by the applicants, reviewers and Scientific Review Committee, the following grants will be funded:
Benoit D’Autreaux, Paris-Saclay University: “Cell-free high throughput screening assays for the discovery of compounds replacing frataxin in FA”
Hélène Puccio, the Institut de Génétique et de Biologie Moléculaire et Cellulaire: “Characterization of new humanized mouse model (TG(FXN)YG8Pook/800J) carrying 650-800 GAA repeats”
Mirella Dottori, University of Wollongong: “Nanoparticle-mediated gene delivery of frataxin to neurons”
Massimo Pandolfo, Université Libre de Bruxelles (ULB), Hôpital Erasme:“Induced pluripotent stem cells-derived neurons for translational research in Friedreich ataxia"
FARA's most recent grant round was of very high quality, and included some very innovative research. After much work by the applicants, reviewers and Scientific Review Committee, the following grants will be funded:
Benoit D’Autreaux, Paris-Saclay University: “Cell-free high throughput screening assays for the discovery of compounds replacing frataxin in FA”
Hélène Puccio, the Institut de Génétique et de Biologie Moléculaire et Cellulaire: “Characterization of new humanized mouse model (TG(FXN)YG8Pook/800J) carrying 650-800 GAA repeats”
Mirella Dottori, University of Wollongong: “Nanoparticle-mediated gene delivery of frataxin to neurons”
Massimo Pandolfo, Université Libre de Bruxelles (ULB), Hôpital Erasme:“Induced pluripotent stem cells-derived neurons for translational research in Friedreich ataxia"
Muscular Dystrophy Association Awards 25 Grants Totaling More Than $6.6 Million for Neuromuscular Disease Research
NEW YORK, Sept. 5, 2019 /PRNewswire. NEWS PROVIDED BY: Muscular Dystrophy Association, Sep 05, 2019.
Critical funding provided by MDA will support studies to further understand disease mechanisms, optimize and build upon existing therapies, and advance drug target identification, especially toward gene-targeted therapies -- research that will have translational and clinical application across many neuromuscular diseases
Jordi Magrane, PhD
Weill Cornell Medical College
Research grant, $300,000
Cell and non-cell autonomous effects of frataxin deficiency in FA pathophysiology
Critical funding provided by MDA will support studies to further understand disease mechanisms, optimize and build upon existing therapies, and advance drug target identification, especially toward gene-targeted therapies -- research that will have translational and clinical application across many neuromuscular diseases
Jordi Magrane, PhD
Weill Cornell Medical College
Research grant, $300,000
Cell and non-cell autonomous effects of frataxin deficiency in FA pathophysiology
Friedreich ataxia- pathogenesis and implications for therapies
Martin B. Delatycki, Sanjay I. Bidichandani, Neurobiology of Disease, 2019, 104606, doi: 10.1016/j.nbd.2019.104606.
Therapies that have been proposed include pharmaceuticals that increase frataxin levels, protein and gene replacement therapies, antioxidants, iron chelators and modulators of inflammation. Whilst no therapies have yet been approved for Friedreich ataxia, there is much optimism that the advances in the understanding of the pathogenesis of this disorder since the discovery its genetic basis, will result in approved disease modifying therapies in the near future.
Therapies that have been proposed include pharmaceuticals that increase frataxin levels, protein and gene replacement therapies, antioxidants, iron chelators and modulators of inflammation. Whilst no therapies have yet been approved for Friedreich ataxia, there is much optimism that the advances in the understanding of the pathogenesis of this disorder since the discovery its genetic basis, will result in approved disease modifying therapies in the near future.
Wednesday, September 4, 2019
An Affordable Method for Evaluation of Ataxic Disorders Based on Electrooculography
Alberto López, Francisco Ferrero, Octavian Postolache; Sensors 2019, 19(17), 3756; doi:10.3390/s19173756
This paper reports an affordable ataxic disorders evaluation method based on the processing of EOG, which could be used to replace the traditional naked-eye method. The EOG, combined with a computer application, may be a useful for testing a patient’s eye coordination and identifying whether the subject might have some type of ataxia. The results obtained show the feasibility of the proposed method as a promising clinical assessment modality for performing an objective evaluation. However, signal processing and parameter setting improvements are necessary.
This paper reports an affordable ataxic disorders evaluation method based on the processing of EOG, which could be used to replace the traditional naked-eye method. The EOG, combined with a computer application, may be a useful for testing a patient’s eye coordination and identifying whether the subject might have some type of ataxia. The results obtained show the feasibility of the proposed method as a promising clinical assessment modality for performing an objective evaluation. However, signal processing and parameter setting improvements are necessary.
Tuesday, September 3, 2019
Hepcidin and its therapeutic potential in neurodegenerative disorders
Qian, Z‐M, Ke, Y.; Med Res Rev. 2019; 1‐ 21. Doi:10.1002/med.21631
Reducing iron toward normal levels or hampering the increases in iron associated with age in the brain is a promising therapeutic strategy for all iron‐related neurodegenerative disorders. Hepcidin is a crucial regulator of iron homeostasis in the brain. Recent studies have suggested that upregulating brain hepcidin levels can significantly reduce brain iron content through the regulation of iron transport protein expression in the blood‐brain barrier and in neurons and astrocytes. In this review, we focus on the discussion of the therapeutic potential of hepcidin in iron‐associated neurodegenerative diseases and also provide a systematic overview of recent research progress on how misregulated brain iron metabolism is involved in the development of multiple neurodegenerative disorders.
Reducing iron toward normal levels or hampering the increases in iron associated with age in the brain is a promising therapeutic strategy for all iron‐related neurodegenerative disorders. Hepcidin is a crucial regulator of iron homeostasis in the brain. Recent studies have suggested that upregulating brain hepcidin levels can significantly reduce brain iron content through the regulation of iron transport protein expression in the blood‐brain barrier and in neurons and astrocytes. In this review, we focus on the discussion of the therapeutic potential of hepcidin in iron‐associated neurodegenerative diseases and also provide a systematic overview of recent research progress on how misregulated brain iron metabolism is involved in the development of multiple neurodegenerative disorders.
Monday, September 2, 2019
Multifunctional radical quenchers as potential therapeutic agents for the treatment of mitochondrial dysfunction
Xun Ji, Omar M Khdour & Sidney M Hecht; FUTURE MEDICINAL CHEMISTRYVOL. 11, NO. 13; Published Online:30 Aug 2019 doi:10.4155/fmc-2018-0481
Mitochondrial dysfunction is associated with a wide range of human diseases, including neurodegenerative diseases, and is believed to cause or contribute to the etiology of these diseases. These disorders are frequently associated with increased levels of reactive oxygen species. One of the design strategies for therapeutic intervention involves the development of novel small molecules containing redox cores, which can scavenge reactive oxygen radicals and selectively block oxidative damage to the mitochondria. Presently, we describe recent research dealing with multifunctional radical quenchers as antioxidants able to scavenge reactive oxygen radicals. The review encompasses ubiquinone and tocopherol analogs, as well as novel pyri(mi)dinol derivatives, and their ability to function as protective agents in cellular models of mitochondrial diseases.
Mitochondrial dysfunction is associated with a wide range of human diseases, including neurodegenerative diseases, and is believed to cause or contribute to the etiology of these diseases. These disorders are frequently associated with increased levels of reactive oxygen species. One of the design strategies for therapeutic intervention involves the development of novel small molecules containing redox cores, which can scavenge reactive oxygen radicals and selectively block oxidative damage to the mitochondria. Presently, we describe recent research dealing with multifunctional radical quenchers as antioxidants able to scavenge reactive oxygen radicals. The review encompasses ubiquinone and tocopherol analogs, as well as novel pyri(mi)dinol derivatives, and their ability to function as protective agents in cellular models of mitochondrial diseases.
Sunday, September 1, 2019
The Working Life of People with Degenerative Cerebellar Ataxia
A. Ranavolo, M. Serrao, T. Varrecchia, C. Casali, A. Filla, A. Roca, A. Silvetti, C. Marcotulli, B. M. Rondinone, S. Iavicoli, F. Draicchio; Cerebellum (2019). doi:10.1007/s12311-019-01065-x
Supporting patients with ataxia to find an appropriate job is an important priority because about 78% of non-workers search for a job and workers and non-workers have the same potential work abilities (no relevant differences were found in terms of disease characteristics, gender, and work resilience). In this view, introducing non-workers to work-life may have a potential rehabilitative aspect. Findings of this study highlight that equal job opportunities for subjects affected by cerebellar ataxia are recommended.
Supporting patients with ataxia to find an appropriate job is an important priority because about 78% of non-workers search for a job and workers and non-workers have the same potential work abilities (no relevant differences were found in terms of disease characteristics, gender, and work resilience). In this view, introducing non-workers to work-life may have a potential rehabilitative aspect. Findings of this study highlight that equal job opportunities for subjects affected by cerebellar ataxia are recommended.
Saturday, August 31, 2019
Very-late-onset Friedreich’s ataxia: diagnosis in a kindred with late-onset cerebellar ataxia
Conor Fearon, Roisin Lonergan, Damien Ferguson, Susan Byrne, David Bradley, Yvonne Langan, Janice Redmond; Practical Neurology Published Online First: 29 August 2019. doi: 10.1136/practneurol-2019-002368
Friedreich’s ataxia is classically considered a disease with onset in the first or second decade. However, late-onset (age of onset 25–39 years) and very-late-onset (age of onset >40 years) forms do occur rarely. Misdiagnosis is common, particularly because the later onset forms of Friedreich’s ataxia commonly do not show characteristic features of the disorder (areflexia, dysarthria, sensory neuropathy, extensor plantars, amyotrophy, cardiac involvement, diabetes mellitus, scoliosis). Also, there may be atypical features such as spasticity, brisk reflexes and laryngeal dystonia. We present the clinical, imaging and genetic findings of a kindred with very-late-onset Friedreich’s ataxia and discuss the pitfalls and risk of misdiagnosis.
Friedreich’s ataxia is classically considered a disease with onset in the first or second decade. However, late-onset (age of onset 25–39 years) and very-late-onset (age of onset >40 years) forms do occur rarely. Misdiagnosis is common, particularly because the later onset forms of Friedreich’s ataxia commonly do not show characteristic features of the disorder (areflexia, dysarthria, sensory neuropathy, extensor plantars, amyotrophy, cardiac involvement, diabetes mellitus, scoliosis). Also, there may be atypical features such as spasticity, brisk reflexes and laryngeal dystonia. We present the clinical, imaging and genetic findings of a kindred with very-late-onset Friedreich’s ataxia and discuss the pitfalls and risk of misdiagnosis.
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