R. Bhidayasiri, Reference Module in Neuroscience and Biobehavioral Psychology, Elsevier, 2017, ISBN 9780128093245, doi:10.1016/B978-0-12-809324-5.00596-4.
Detailed genetic and family studies emphasize the potential heterogeneity in presenting phenotype as well as age of onset of patients with FRDA. The discovery of the frataxin gene has allowed genotype–phenotype correlations and confirmation that the FRDA expansion is responsible for classical FRDA, late-onset FRDA (LOFA), Friedreich's ataxia with retained reflexes (FARR), and Acadian ataxia.
Therapeutic approaches aimed at improving mitochondrial functioning and to increase frataxin expression, which may have lead to new realistic treatments in the future.
Saturday, January 14, 2017
Friday, January 13, 2017
Friedreich Ataxia: Hypoplasia of Spinal Cord and Dorsal Root Ganglia
Arnulf H. Koeppen MD, Alyssa B. Becker BA, Jiang Qian MD, PhD, Paul J. Feustel PhD. Journal of Neuropathology & Experimental Neurology, DOI:10.1093/jnen/nlw111, First published online: 12 January 2017
The FA patients included a wide range of disease onset and duration suggesting that the SC undergoes growth arrest early and remains abnormally small throughout life. The results strongly support the conclusion that these neural tissues are small because of hypoplasia rather than atrophy and that their developmental delay occurs independently.
It is of interest that Friedreich had already proposed in 1877 that smallness of the clavae (gracile and cuneate nuclei) was developmental.
The FA patients included a wide range of disease onset and duration suggesting that the SC undergoes growth arrest early and remains abnormally small throughout life. The results strongly support the conclusion that these neural tissues are small because of hypoplasia rather than atrophy and that their developmental delay occurs independently.
It is of interest that Friedreich had already proposed in 1877 that smallness of the clavae (gracile and cuneate nuclei) was developmental.
Thursday, January 12, 2017
New hearts for Friedreich patients
David Pleasure, Journal of the Neurological Sciences, Available online 12 January 2017, ISSN 0022-510X, doi:10.1016/j.jns.2017.01.035.
Editorial
The impact of the transplanted hearts on quality of life was large. The transplanted hearts showed no signs of cardiomyopathy during decades-long post-transplantation followup, providing strong evidence that FRDA cardiomyopathy develops independently of other manifestations of this systemic disease.
Editorial
The impact of the transplanted hearts on quality of life was large. The transplanted hearts showed no signs of cardiomyopathy during decades-long post-transplantation followup, providing strong evidence that FRDA cardiomyopathy develops independently of other manifestations of this systemic disease.
Wednesday, January 11, 2017
Cardiac transplantation in Friedreich ataxia: Extended follow-up
Ashley McCormick, Julianna Shinnick, Kim Schadt, Rose Rodriguez, Linda Addonizio, Michio Hirano, Susan Perlman, Kimberly Y. Lin, David R Lynch, Journal of the Neurological Sciences, Available online 10 January 2017, ISSN 0022-510X, doi:10.1016/j.jns.2017.01.027.
Observations emphasize that the rate and nature of progression to end stage heart failure in ndividuals with FRDA is highly variable and, at least in these unusual individuals, not easily predicted by their neurologic status or GAA triplet repeat length. Our case series demonstrates the safety and efficacy of heart transplantations as a possible treatment option for end-stage heart failure in the setting of neurologic disease in both early-and late-onset individuals.
Diagnosis of FRDA should not be viewed as an absolute contraindication that would negatively impact a patient’s candidacy for heart transplantation or re-transplantation.
Observations emphasize that the rate and nature of progression to end stage heart failure in ndividuals with FRDA is highly variable and, at least in these unusual individuals, not easily predicted by their neurologic status or GAA triplet repeat length. Our case series demonstrates the safety and efficacy of heart transplantations as a possible treatment option for end-stage heart failure in the setting of neurologic disease in both early-and late-onset individuals.
Diagnosis of FRDA should not be viewed as an absolute contraindication that would negatively impact a patient’s candidacy for heart transplantation or re-transplantation.
Tuesday, January 10, 2017
Catalent to Develop Softgel Capsules for JOT’s Leading Orphan Disease Candidates
Catalent. Somerset, N.J. (PRWEB) January 09, 2017 . Catalent Pharma Solutions, the leading global provider of advanced delivery technologies and development solutions for drugs, biologics and consumer health products, today announced that it is to evaluate Jupiter Orphan Therapeutics, Inc.’s (JOT) novel formulation of resveratrol, JOTROL, for delivery using Catalent’s R.P. Scherer softgel technology. Under the agreement, Catalent will assess different softgel delivery technologies for JOTROL to determine the optimum oral dosage form, before going on to manufacture doses for human PK studies and Phase II clinical studies.
JOTROL, which is being developed to remedy resveratrol’s poor bioavailability and dose limiting gastrointestinal side effects, is being studied in multiple pre-clinical and clinical trial programs in progress for the treatment of rare diseases linked to single gene deficiencies. These include Friedreich’s Ataxia and Mucopolysaccharide (MPS) diseases, as well as partner programs for treatments in pancreatic cancer, Machado-Joseph and Alzheimer’s disease.
JOTROL, which is being developed to remedy resveratrol’s poor bioavailability and dose limiting gastrointestinal side effects, is being studied in multiple pre-clinical and clinical trial programs in progress for the treatment of rare diseases linked to single gene deficiencies. These include Friedreich’s Ataxia and Mucopolysaccharide (MPS) diseases, as well as partner programs for treatments in pancreatic cancer, Machado-Joseph and Alzheimer’s disease.
Sunday, January 8, 2017
Impact of cerebellar atrophy on cortical gray matter and cerebellar peduncles as assessed by voxel-based morphometry and high angular resolution diffusion imaging
Dayan M., Olivito G., Molinari M., Cercignani M., Bozzali M., Leggio M.,Functional Neurology 2016; 31(3)
Structural and dMRI data of seven patients with cerebellar atrophy (2 with spinocerebellar atrophy type 2, 1 with Friedreich’s ataxia, 4 with idiopathic cerebellar ataxia) and no visible cortical lesions or cortical atrophy were investigated with Freesurfer and voxel-based morphometry (VBM) of gray matter (GM) as well as MCP and SCP FA maps. The significant difference in the MCP and SCP dMRI metrics between patients and controls as well as the significant correlation with ataxia total score and subscores support the use of dMRI metrics as an imaging biomarker for cerebellar degeneration and ataxia.
Structural and dMRI data of seven patients with cerebellar atrophy (2 with spinocerebellar atrophy type 2, 1 with Friedreich’s ataxia, 4 with idiopathic cerebellar ataxia) and no visible cortical lesions or cortical atrophy were investigated with Freesurfer and voxel-based morphometry (VBM) of gray matter (GM) as well as MCP and SCP FA maps. The significant difference in the MCP and SCP dMRI metrics between patients and controls as well as the significant correlation with ataxia total score and subscores support the use of dMRI metrics as an imaging biomarker for cerebellar degeneration and ataxia.
Saturday, January 7, 2017
A new case of complete primary cerebellar agenesis: clinical and imaging findings in a living patient
Feng Yu, Qing-jun Jiang, Xi-yan Sun, Rong-wei Zhang; Brain, Volume 138, Issue 6, 1 June 2015 DOI:10.1093/brain/awu239
DON’T mind the gap. A woman has reached the age of 24 without anyone realising she was missing a large part of her brain. The case highlights just how adaptable the organ is. Woman of 24 found to have no cerebellum in her brain, however, in this woman, the missing cerebellum resulted in only mild to moderate motor deficiency, and mild speech problems such as slightly slurred pronunciation. Her doctors describe these effects as “less than would be expected”, and say her case highlights the remarkable plasticity of the brain.
Cerebellar agenesis is an extremely rare condition implying complete absence of the cerebellum.
DON’T mind the gap. A woman has reached the age of 24 without anyone realising she was missing a large part of her brain. The case highlights just how adaptable the organ is. Woman of 24 found to have no cerebellum in her brain, however, in this woman, the missing cerebellum resulted in only mild to moderate motor deficiency, and mild speech problems such as slightly slurred pronunciation. Her doctors describe these effects as “less than would be expected”, and say her case highlights the remarkable plasticity of the brain.
Cerebellar agenesis is an extremely rare condition implying complete absence of the cerebellum.
Friday, January 6, 2017
Otoneurological Abnormalities in Patients with Friedreich's Ataxia
Zeigelboim BS, Mesti JC, Fonseca VR, Faryniuk JH, Marques JM, Cardoso RC, Teive HA. Int Arch Otorhinolaryngol. 2017 Jan;21(1):79-85. doi: 10.1055/s-0036-1572529.
The most prevalent otoneurological symptoms were incoordination of movement, gait imbalance, and dizziness. Alterations in the vestibular examination occurred in 90% of patients, located mainly in the caloric test, with a predominance of deficient central vestibular system dysfunction.
The study emphasizes the importance of the vestibular evaluation for the topographic diagnosis of neurodegenerative diseases since, in most cases, the otoneurological symptoms present early and such information may aid in the choice of procedures to be performed in clinical and therapeutic monitoring.
The most prevalent otoneurological symptoms were incoordination of movement, gait imbalance, and dizziness. Alterations in the vestibular examination occurred in 90% of patients, located mainly in the caloric test, with a predominance of deficient central vestibular system dysfunction.
The study emphasizes the importance of the vestibular evaluation for the topographic diagnosis of neurodegenerative diseases since, in most cases, the otoneurological symptoms present early and such information may aid in the choice of procedures to be performed in clinical and therapeutic monitoring.
Thursday, January 5, 2017
Synthetic genome readers target clustered binding sites across diverse chromatin states
Graham S. Erwin, Matthew P. Grieshop, Devesh Bhimsaria, Truman J. Do, José A. Rodríguez-Martínez, Charu Mehta, Kanika Khanna, Scott A. Swanson, Ron Stewart, James A. Thomson, Parameswaran Ramanathan, and Aseem Z. Ansari; PNAS 2016 113 (47) E7418-E7427; published ahead of print November 8, 2016, doi: 10.1073/pnas.1604847113
The linear polyamide (3) studied here was designed to bind to GAA repeats in the first intron of frataxin, a locus that appears to be situated within heterochromatin marked by H3K9me3. Taken together, the ability of polyamides to access heterochromatin (a major barrier to binding to natural and artificial DNA-binding factors) opens unique opportunities to deploy this class of synthetic genome readers to regulate gene networks that direct cellular fate and function. Linear 3, designed to target 5′-AAGAAGAAG-3′, is designed to target a GAA repeat expansion found in patients with Friedreich’s ataxia to alleviate transcriptional repression.
The COSMIC-seq approach that we describe here is a robust and broadly applicable method that can be readily extended to map the genome-wide binding properties of other classes of DNAbinding molecules, including several genome-directed therapeutics. COSMIC-seq will be instrumental in the genome-guided design of molecules that serve as precision-targeted therapeutics.
The linear polyamide (3) studied here was designed to bind to GAA repeats in the first intron of frataxin, a locus that appears to be situated within heterochromatin marked by H3K9me3. Taken together, the ability of polyamides to access heterochromatin (a major barrier to binding to natural and artificial DNA-binding factors) opens unique opportunities to deploy this class of synthetic genome readers to regulate gene networks that direct cellular fate and function. Linear 3, designed to target 5′-AAGAAGAAG-3′, is designed to target a GAA repeat expansion found in patients with Friedreich’s ataxia to alleviate transcriptional repression.
The COSMIC-seq approach that we describe here is a robust and broadly applicable method that can be readily extended to map the genome-wide binding properties of other classes of DNAbinding molecules, including several genome-directed therapeutics. COSMIC-seq will be instrumental in the genome-guided design of molecules that serve as precision-targeted therapeutics.
Wednesday, January 4, 2017
A wearable proprioceptive stabilizer for rehabilitation of limb and gait ataxia in hereditary cerebellar ataxias: a pilot open-labeled study
Luca Leonardi, Maria Gabriella Aceto, Christian Marcotulli, Giuseppe Arcuria, Mariano Serrao, Francesco Pierelli, Paolo Paone, Alessandro Filla, Alessandro Roca, Carlo Casali. Neurol Sci (2016). First Online: 31 December 2016 doi:10.1007/s10072-016-2800-x
The aim of this pilot study is to test the feasibility and effectiveness of a wearable proprioceptive stabilizer that emits focal mechanical vibrations in patients affected by hereditary cerebellar ataxias. This small open-labeled study shows preliminary evidence that focal mechanical vibration exerted by a wearable proprioceptive stabilizer might improve limb and gait ataxia in patients affected by hereditary cerebellar ataxias.
The aim of this pilot study is to test the feasibility and effectiveness of a wearable proprioceptive stabilizer that emits focal mechanical vibrations in patients affected by hereditary cerebellar ataxias. This small open-labeled study shows preliminary evidence that focal mechanical vibration exerted by a wearable proprioceptive stabilizer might improve limb and gait ataxia in patients affected by hereditary cerebellar ataxias.
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