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.
Tuesday, January 10, 2017
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.
Tuesday, January 3, 2017
CN Project OPUS10: “Role of microRNAs in regulation iron metabolism in Friedreich's ataxia”
biotechnologia.pl; Prof. Włodzimierz Krzyżosiak, Institute of Bioorganic Chemistry PAS, Polish Academy of Sciences.(2017-01-02)
The goals of this project are to define changes in the expression and activity of microRNAs in FRDA, and analyze how these abnormalities affect the activity of genes which are responsible for the localization and amount of iron in neuronal and heart cells of patients with Friedreich’s ataxia. We will define relationship between miRNA molecules and iron availability. We will also uncover the pattern of detectable microRNA molecules that is specific to FRDA.
The goals of this project are to define changes in the expression and activity of microRNAs in FRDA, and analyze how these abnormalities affect the activity of genes which are responsible for the localization and amount of iron in neuronal and heart cells of patients with Friedreich’s ataxia. We will define relationship between miRNA molecules and iron availability. We will also uncover the pattern of detectable microRNA molecules that is specific to FRDA.
Monday, January 2, 2017
Percutaneous needle tenotomy for the treatment of muscle and tendon contractures in adults with brain damage: results and complications
Flavia Coroian, Claire Jourdan, Jérome Froger, Claire Anquetil, Olivier Choquet, Bertand Coulet, Isabelle Laffont, Archives of Physical Medicine and Rehabilitation, Available online 18 December 2016, ISSN 0003-9993, doi:10.1016/j.apmr.2016.11.014.
In our series, percutaneous needle tenotomy procedures under local or locoregional anesthesia were performed by a PM&R physician trained by an orthopedic surgeon and yielded very few complications. This technique seems relevant for contractures of several superficial tendons for the upper and lower limb alike. Furthermore, this technique gives a satisfactory orthopedic outcome fulfilling non-functional objectives (hygiene, pain, nursing) and even functional ones for a small number of well-selected patients (gait, grip, daily life).
PNT yields good results in the management of superficial muscle and tendon contractures in selected brain-damaged patients. The complications rate is very low and this treatment can be an alternative to conventional surgery in frail neurological patients.
In our series, percutaneous needle tenotomy procedures under local or locoregional anesthesia were performed by a PM&R physician trained by an orthopedic surgeon and yielded very few complications. This technique seems relevant for contractures of several superficial tendons for the upper and lower limb alike. Furthermore, this technique gives a satisfactory orthopedic outcome fulfilling non-functional objectives (hygiene, pain, nursing) and even functional ones for a small number of well-selected patients (gait, grip, daily life).
PNT yields good results in the management of superficial muscle and tendon contractures in selected brain-damaged patients. The complications rate is very low and this treatment can be an alternative to conventional surgery in frail neurological patients.
Sunday, January 1, 2017
Gene therapy: Gene-editing therapy for neurological disease
Moira A. McMahon & Don W. Cleveland. Nature Reviews Neurology 13, 7–9 (2017) doi:10.1038/nrneurol.2016.190 Published online 16 December 2016.
Guide RNA-mediated CRISPR–Cas nucleases are a powerful technology for the engineering of mammalian genomes. CRISPR–Cas9-dependent editing of mutated genes that cause Huntington disease and fragile X syndrome was recently achieved in cell-based models, heralding the first step towards developing this technology into viable therapeutics for neurological diseases.
The successful translation of these proof‑of‑principle studies to in vivo gene editing is eagerly anticipated, but several challenges remain. One major challenge is delivery of the sgRNA and nuclease to target cells. A final major challenge for extension of gene-editing approaches to applications within the nervous system is the efficiency of gene silencing or correction: can the changes be made in sufficient numbers of cells to alter the disease course?.
What seems certain is that continued development of genome-editing technology to target neurological diseases is likely to provide a greater understanding of the diseases themselves and, hopefully, will one day form the basis of a successful therapy.
Guide RNA-mediated CRISPR–Cas nucleases are a powerful technology for the engineering of mammalian genomes. CRISPR–Cas9-dependent editing of mutated genes that cause Huntington disease and fragile X syndrome was recently achieved in cell-based models, heralding the first step towards developing this technology into viable therapeutics for neurological diseases.
The successful translation of these proof‑of‑principle studies to in vivo gene editing is eagerly anticipated, but several challenges remain. One major challenge is delivery of the sgRNA and nuclease to target cells. A final major challenge for extension of gene-editing approaches to applications within the nervous system is the efficiency of gene silencing or correction: can the changes be made in sufficient numbers of cells to alter the disease course?.
What seems certain is that continued development of genome-editing technology to target neurological diseases is likely to provide a greater understanding of the diseases themselves and, hopefully, will one day form the basis of a successful therapy.
Saturday, December 31, 2016
Clinical trials: To catch a crook, you might try statistics
Gary R. Cutter; Nature Reviews Neurology 13, 9–10 (2017) doi:10.1038/nrneurol.2016.194 Published online 16 December 2016
To reduce research fraud, we need to understand more deeply why professional researchers and clinicians commit fraud. Certainly, personal interest is a major factor. Review boards thoroughly assess conflicts of interest to protect authors from gaining excess monetary gains via publications, but we have little to protect against advancing one’s personal interests — indeed, we reward it. Promotions, grants and grant renewals all depend on publications. Moreover, researchers might commit fraud for more egotistic reasons than mere survival in their chosen career, such as for money or to get a product on the market, to boost the market value of their start‑up company, or perhaps even to deliberately sabotage competitors.
Making trial and other experimental data publicly available have been suggested as one
strategy to reduce fraud, as any interested individual could search for evidence, thereby making fraud less tempting. However, the consequences of the false positives should be kept in mind: do we wish to impugn even one honest researcher in our attempts to catch dishonest ones?.
To reduce research fraud, we need to understand more deeply why professional researchers and clinicians commit fraud. Certainly, personal interest is a major factor. Review boards thoroughly assess conflicts of interest to protect authors from gaining excess monetary gains via publications, but we have little to protect against advancing one’s personal interests — indeed, we reward it. Promotions, grants and grant renewals all depend on publications. Moreover, researchers might commit fraud for more egotistic reasons than mere survival in their chosen career, such as for money or to get a product on the market, to boost the market value of their start‑up company, or perhaps even to deliberately sabotage competitors.
Making trial and other experimental data publicly available have been suggested as one
strategy to reduce fraud, as any interested individual could search for evidence, thereby making fraud less tempting. However, the consequences of the false positives should be kept in mind: do we wish to impugn even one honest researcher in our attempts to catch dishonest ones?.
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