Central Nervous System Involvement as Outcome Measure for Clinical Trials Efficacy in Myotonic Dystrophy Type 1

Increasing evidences indicate that in Myotonic Dystrophy type 1 (DM1 or Steinert disease), an autosomal dominant multisystem disorder caused by a (CTG)n expansion in DMPK gene on chromosome 19q13. 3, is the most common form of inherited muscular dystrophy in adult patients with a global prevalence of 1/8000, and involvement of the central nervous system can be included within the core clinical manifestations of the disease. Variable in its severity and progression rate over time, likely due to the underlying causative molecular mechanisms; this component of the clinical picture presents with high heterogeneity involving cognitive and behavioral alterations, but also sensory-motor neural integration, and in any case, significantly contributing to the disease burden projected to either specific functional neuropsychological domains or quality of life as a whole. Principle manifestations include alterations of the frontal lobe function, which is more prominent in patients with an early onset, such as in congenital and childhood onset forms, here associated with severe intellectual disabilities, speech and language delay and reduced IQ-values, while in adult onset DM1 cognitive and neuropsychological findings are usually not so severe. Different methods to assess central nervous system involvement in DM1 have then recently been developed, these ranging from more classical psychometric and cognitive functional instruments to sophisticated psycophysic, neurophysiologic and especial...
Source: Frontiers in Neurology - Category: Neurology Source Type: research

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Abstract PURPOSE: In patients with Duchenne muscular dystrophy (DMD), weakness of the upper limb (UL) muscles has a significant impact on daily activities and body functions. This problem necessitates a screening tool that can be used quickly and easily in clinical situations, such as the Upper Limb Short Questionnaire (ULSQ). However, its validity and reliability as a clinical measure have not yet been evaluated. MATERIALS AND METHODS: The ULSQ was initially administered in face-to-face interviews, and then by telephone four weeks later. Lower limb and UL body functions were assessed by the Vignos and modifi...
Source: Disability and Rehabilitation - Category: Rehabilitation Authors: Tags: Disabil Rehabil Source Type: research
AbstractIn India, Rights of persons with disabilities (RPWD) Act 2016 recognizes 21 disabilities including 12 disabilities which were not present in Person with disabilities Act 1995. Disability certificate (DC) is necessary to avail benefits under the RPWD Act 2016. To study socio-demographic and clinical profile of patients who were issued DC as per RPWD Act 2016 for psychiatric, neurological, and neurosurgical disorders.  The study was carried out at National Institute for Mental Health and Neurological Sciences (NIMHANS), Bengaluru. Socio-demographic and clinical details of patients who were issued DC for 2107 and...
Source: Journal of Psychosocial Rehabilitation and Mental Health - Category: Psychiatry Source Type: research
We aimed to identify the symptoms that most impact quality of life in individuals with limb girdle muscular dystrophy (LGMD). LGMD is a group of multisystem disorders impairing the physical, mental, and social health of patients while inflicting significant disability. The identification of the symptoms and manifestations most significant to a patient's health and the relationship between these issues and patient characteristics are lacking in LGMD. LGMD-affected individuals from patient registries (JAIN foundation, C3 registry, and global FKRP registry) that include both mixed LGMD and disease specific patient populations...
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
Facioscapulohumeral muscular dystrophy (FSHD) is caused by loss of repression at the D4Z4 locus resulting in aberrant expression of the homeobox transcription factor DUX4. DUX4 expression activates its downstream transcriptional program resulting in cell death, skeletal muscle loss and progressive motor disability. Fulcrum Therapeutics is developing losmapimod to treat FSHD at its root cause. Losmapimod is a potent and highly selective small molecule inhibitor of p38 α/β that in preclinical studies reduced DUX4 activity and its downstream transcriptional program in FSHD myotubes resulting in the prevention of ce...
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
Inositol polyphosphate-5-phosphatase K [INPP5K (MIM: 607875)] acts as a PIP3 5-phosphatase and regulates actin cytoskeleton, insulin, and cell migration. Biallelic pathogenic variants in INPP5K have recently been reported in patients affected by a form of muscular dystrophy with childhood onset. Affected patients have limb girdle muscle weakness, often associated with bilateral cataracts, short stature, and intellectual disability. Here we report four patients affected by INPP5K-related muscle dystrophy, who were apparently unrelated but originated from the same geographical area in South Italy. These patients manifest a r...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Basel, 11 September 2020 – Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced new data that show OCREVUS® (ocrelizumab) is a highly effective treatment option for people with relapsing-remitting multiple sclerosis (RRMS) who experienced a suboptimal response to their prior disease modifying therapy (DMT). Subgroup analys is from the two-year open-label Phase IIIb CASTING study also demonstrates that patients benefit across a wide range of disease related and demographic subgroups, regardless of prior treatment background. Findings will be presented at MSVirtual2020, the 8th Joint Meeting of the Americas Committee...
Source: Roche Media News - Category: Pharmaceuticals Source Type: news
Basel, 10 September 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) will present new ENSPRYNG ® (satralizumab) data on reducing relapse severity in the treatment of neuromyelitis optica spectrum disorder (NMOSD), a rare disease of the central nervous system. These data are being presented at MSVirtual2020, the 8th joint ACTRIMS-ECTRIMS meeting, in addition to longer-term efficacy data supporting the continued effect of ENSPRYNG on reducing the risk of NMOSD relapse, as well as its favourable benefit:risk profile.“The data for ENSPRYNG at MSVirtual2020 are promising and suggest it significantly reduces relapse severity ...
Source: Roche Media News - Category: Pharmaceuticals Source Type: news
Basel, 9 September 2020 – Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced the initiation of an innovative Phase III clinical trial programme for its investigational medicine fenebrutinib in multiple sclerosis (MS), along with a higher-dose Phase III clinical trial programme for OCREVUS® (ocrelizumab) and a distinct O CREVUS trial specifically to support African-American and Hispanic- and Latinx-American patients with MS. Overviews of clinical trials and scientific rationale will be presented at MSVirtual2020, the 8th Joint Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTR...
Source: Roche Media News - Category: Pharmaceuticals Source Type: news
CONCLUSIONS: PWSD is a mobility option that offers choice, control and opportunity for independence. This consensus statement can assist clinicians with decision-making around factors influencing successful implementation and optimisation of PWSD for young people with DMD. Implications for Rehabilitation Tolerance and comfort in supported standing for at least 10 minutes, ankle contracture limited to less than 10 degrees and the child's goals reflecting motivation to use the standing position were agreed to be necessary considerations in guiding the decision to trial a PWSD. Trialling a PWSD when the child is predic...
Source: Disability and Rehabilitation - Category: Rehabilitation Authors: Tags: Disabil Rehabil Source Type: research
This study aims to assess 12-month changes in lower-limb strength, muscle size, body composition and physical activity in adults with Muscular Dystrophy (MD). METHODS: Adult males with Duchenne MD (DMD; N = 15) and Beckers MD (BMD; N = 12) were assessed at baseline and 12-months for body composition (Body fat and lean body mass (LBM)), Isometric maximal voluntary contraction (Knee-Extension (KEMVC) and Plantar-Flexion (PFMVC)) and physical activity (tri-axial accelerometry). RESULTS: 12-Month change in strength was found as -19% (PFMVC) and -14% (KEMVC) in DMD. 12-Month change in stren...
Source: Disability and Rehabilitation - Category: Rehabilitation Authors: Tags: Disabil Rehabil Source Type: research
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