State biomarkers for Machado Joseph disease: Validation, feasibility and responsiveness to change

We present here a review of studies on peripheral and neurophysiological markers in SCA3/MJD that can be candidates for state biomarkers. Data on markers already studied were summarized, giving emphasis on validation against clinical scale, and responsiveness to change. While some biological fluid compounds and neurophysiological parameters showed poor responsiveness, others seemed to be good candidates. Some potential candidates that are waiting for responsiveness studies were serum levels of neuron specific enolase, vestibulo-ocular reflex and video-oculography. Candidates evaluated by RNA and microRNA expression levels need further studies to improve their measurements. Data on peripheral levels of Beclin-1 and DNAJB1 are promising but still incipient. We conclude that several potential candidates should follow onto validating studies for surrogate state biomarkers of SCA3/MJD.
Source: Genetics and Molecular Biology - Category: Genetics & Stem Cells Source Type: research

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AbstractCerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recently described slowly progressive ataxia with severe imbalance due to the compromise of three of the four sensory inputs for balance, leaving only vision unaffected. Bilateral vestibulopathy is present but saccular and utricular function, measured by vestibular evoked myogenic potentials (VEMPs), has not been widely studied in these patients. Dysautonomia has been reported but is not among the diagnostic criteria. We performed a database analysis to identify patients evaluated between 2003 and 2019 with probable diagnosis of CANVA...
Source: The Cerebellum - Category: Neurology Source Type: research
eacute;rez-Fernández N Abstract Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recently described slowly progressive ataxia with severe imbalance due to the compromise of three of the four sensory inputs for balance, leaving only vision unaffected. Bilateral vestibulopathy is present but saccular and utricular function, measured by vestibular evoked myogenic potentials (VEMPs), has not been widely studied in these patients. Dysautonomia has been reported but is not among the diagnostic criteria. We performed a database analysis to identify patients evaluated between 2003 a...
Source: Cerebellum - Category: Neuroscience Authors: Tags: Cerebellum Source Type: research
Publication date: Available online 26 July 2019Source: Progress in NeurobiologyAuthor(s): Camille A. Juźwik, Sienna S. Drake, Yang Zhang, Nicolas Paradis-Isler, Alexandra Sylvester, Alexandre Amar-Zifkin, Chelsea Douglas, Barbara Morquette, Craig S. Moore, Alyson FournierAbstractWhile the root causes for individual neurodegenerative diseases are distinct, many shared pathological features and mechanisms contribute to neurodegeneration across diseases. Altered levels of microRNAs, small non-coding RNAs involved in post transcriptional regulation of gene expression, are reported for numerous neurodegenerative diseases. Yet,...
Source: Progress in Neurobiology - Category: Neuroscience Source Type: research
Conclusions: SCA7 can present with a very mild form of retinal degeneration similar to the classic phenotype of RP1L1-negative OMD in case of the lower number of CAG repeats. PMID: 31269856 [PubMed - as supplied by publisher]
Source: Ophthalmic Genetics - Category: Opthalmology Tags: Ophthalmic Genet Source Type: research
AbstractVestibulo –ocular reflexes (VOR) are mediated by frequency-tuned pathways that separately transform the different dynamic and static aspects of head motion/position-related sensory signals into extraocular motor commands. Voltage-dependent potassium conductances such as those formed by Kv1.1 are important f or the ability of VOR circuit elements to encode highly transient motion components. Here we describe the impact of the Kv1.1 channel blocker 4-aminopyridine (4-AP) on spontaneous and motion-evoked discharge of superior oblique motoneurons. Spike activity was recorded from the motor nerve in isolate d prep...
Source: Journal of Neurology - Category: Neurology Source Type: research
ConclusionIn our study, we observed an improved performance of multi-gene panel testing, with an overall diagnostic yield of 40%. Furthermore, we show that NGS (next-generation sequencing)-based testing is comprehensive and can detect all types of variants including structural variants. It can be considered as a single-platform genetic test for neurological disorders that can provide a swift and definitive diagnosis in a cost-effective manner.
Source: Journal of Neurology - Category: Neurology Source Type: research
This study was carried out in accordance with the recommendations of the National Animal Care and Use Committee of the University of Buenos Aires (CICUAL). The protocol was approved by the CICUAL. Mice were kept under a 12-h light/dark cycle, with controlled temperature (23 ± 2°C) and humidity (40–60%) and had ad libitum access to food and water. To produce hTDP-43 transgenic lines, as described previously (Igaz et al., 2011), pronucleus of fertilized eggs from C57BL/6J × C3HeJ F1 matings were injected with a vector containing hTDP-43-WT cDNA. Monogenic tetO-TDP-WT12 mice wer...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Marco Vacante1, Antonio Biondi1, Francesco Basile1, Roberto Ciuni1, Salvatore Luca1, Salomone Di Saverio2, Carola Buscemi3, Enzo Saretto Dante Vicari3 and Antonio Maria Borzì3* 1Department of General Surgery and Medical-Surgical Specialties, University of Catania, Catania, Italy 2Cambridge Colorectal Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom 3Department of Clinical and Experimental Medicine, Specialization School in Geriatrics, University of Catania, Catania, Italy There is a high prevalence of hypothyroidism in the elderly population, mainly among women. The mo...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
CONCLUSIONS: Here and for the first time, we reported on two previously variant late-infantile neuronal ceroid lipofuscinoses-associated variants in MFSD8 but in association with a form of cone-rod dystrophy known as non-syndromic macular dystrophy with central cone involvement. Our results support this concept that variant late-infantile neuronal ceroid lipofuscinoses and non-syndromic macular dystrophy with central cone involvement are not different disease entities, but rather allelic diseases and phenotypic variants of the same mutation. Consideration of the milder MFSD8 phenotypes is important against the potentially ...
Source: Ophthalmic Genetics - Category: Opthalmology Tags: Ophthalmic Genet Source Type: research
Conclusion The m.10191T>C mutation in the mtDNA of the complex I (CI) subunit of MTND3 results in the substitution of a highly conserved amino acid (p.Ser45Pro) within the ND3 protein, leading to CI dysfunction through impaired enzyme catalysis rather than impaired stability or assembly, causing a broad clinical spectrum of disorders (26). Patients with the m.10191T>C mutation are rare. In the present study, we report on a family of patients with the extremely rare adult-onset Leigh-like syndrome with the m.10191T>C mutation. Including the two patients from our reported family, the m.10191T>C mutation has bee...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
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