Antisense oligonucleotide targeting DMPK in patients with myotonic dystrophy type 1: a multicentre, randomised, dose-escalation, placebo-controlled, phase 1/2a trial.

Background: Myotonic dystrophy type 1 results from an RNA gain-of-function mutation, in which DM1 protein kinase (DMPK) transcripts carrying expanded trinucleotide repeats exert deleterious effects. Antisense oligonucleotides (ASOs) provide a promising approach to treatment of myotonic dystrophy type 1 because they reduce toxic RNA levels. We aimed to investigate the safety of baliforsen (ISIS 598769), an ASO targeting DMPK mRNA.

Milestones of progression in myotonic dystrophy type 1 and type 2.

Introduction/aims: Disease progression in myotonic dystrophy (DM) is marked by milestone events when functional thresholds are crossed. DM type 2 (DM2) is considered less severe than DM type 1 (DM1), but it is unknown whether this applies uniformly to all features. We compared the age-dependent risk for milestone events in DM1 and DM2 and tested for associations with age of onset and sex.

Brief assessment of cognitive function in myotonic dystrophy: Multicenter longitudinal study using computer-assisted evaluation.

Introduction/aims: Myotonic dystrophy type 1 (DM1) is known to affect cognitive function, but the best methods to assess central nervous system involvement in multicenter studies have not been determined. In this study our primary aim was to evaluate the potential of computerized cognitive tests to assess cognition in DM1.

Methods: We conducted a prospective, longitudinal, observational study of 113 adults with DM1 at six sites.

Reproductive Cancer Risk Factors in Women With Myotonic Dystrophy (DM): Survey Data From the US and UK DM Registries.

Recent evidence demonstrates that women with myotonic dystrophy type 1 are at increased risk of reproductive organ tumors. However, studies of reproductive cancer risk factors in those patients are lacking. Using questionnaires, we collected and analyzed personal history information related to cancer risk factors from women enrolled in a UK and US registry for myotonic dystrophy (; DM) patients.

Patient-reported study of the impact of pediatric-onset myotonic dystrophy.

Introduction: The prevalence and impact of symptoms affecting individuals with pediatric forms of myotonic dystrophy type-1 (DM1) are not well understood.

Methods: Patients from the United States, Canada, and Sweden completed a survey that investigated 20 themes associated with pediatric-onset DM1. Participants reported the prevalence and importance of each theme affecting their lives.

Health profile of a cohort of adults with Duchenne muscular dystrophy.

Introduction: As the Duchenne muscular dystrophy (DMD) population ages, it is essential that we understand the late-stage health profile and provide the appropriate care for this emerging population.

Methods: We undertook a descriptive study to document the health profile of a cohort of adults with DMD using data from the Muscular Dystrophy Surveillance Tracking and Research network (MD STARnet). Data included information collected from Arizona, Colorado, Iowa, Georgia, and 12 counties in western New York on individuals born since January 1982 and followed through December 2012.

High frequency of gastrointestinal manifestations in myotonic dystrophy type 1 and type 2.

Objective: To analyze gastrointestinal (GI) manifestations, their progression over time, and medications being used to treat GI symptoms in a large cohort of patients with myotonic dystrophy types 1 (DM1) and 2 (DM2).

Methods: We analyzed patient-reported data and medical records in a national registry cohort at baseline and 5 years.

Results: At baseline, the majority of patients reported trouble swallowing in DM1 (55%; n = 499 of 913) and constipation in DM2 (53%; n = 96 of 180).

Medication adherence in patients with myotonic dystrophy and facioscapulohumeral muscular dystrophy.

Myotonic dystrophy (DM) and facioscapulohumeral muscular dystrophy (FSHD) are the two most common adult muscular dystrophies and have progressive and often disabling manifestations. Higher levels of medication adherence lead to better health outcomes, especially important to patients with DM and FSHD because of their multisystem manifestations and complexity of care. However, medication adherence has not previously been studied in a large cohort of DM type 1 (DM1), DM type 2 (DM2), and FSHD patients.

Efficacy and safety of deflazacort vs prednisone and placebo for Duchenne muscular dystrophy.

Objective: To assess safety and efficacy of deflazacort (DFZ) and prednisone (PRED) vs placebo in Duchenne muscular dystrophy (DMD).

Methods: This phase III, double-blind, randomized, placebo-controlled, multicenter study evaluated muscle strength among 196 boys aged 5-15 years with DMD during a 52-week period. In phase 1, participants were randomly assigned to receive treatment with DFZ 0.

Practice guideline update summary: Corticosteroid treatment of Duchenne muscular dystrophy: Report of the Guideline Development Subcommittee of the American Academy of Neurology.

Objective: To update the 2005 American Academy of Neurology (AAN) guideline on corticosteroid treatment of Duchenne muscular dystrophy (DMD).

Methods: We systematically reviewed the literature from January 2004 to July 2014 using the AAN classification scheme for therapeutic articles and predicated recommendations on the strength of the evidence.

Results: Thirty-four studies met inclusion criteria.

Patient-Reported Impact of Symptoms in Myotonic Dystrophy Type 2 (PRISM-2).

Objective: To determine the frequency and relative importance of the most life-affecting symptoms in myotonic dystrophy type 2 (DM2) and to identify the factors that have the strongest association with these symptoms.

Methods: We conducted a cross-sectional study of adult patients with DM2 from a National Registry of DM2 Patients to assess the prevalence and relative importance of 310 symptoms and 21 symptomatic themes. Participant responses were compared by age categories, sex, educational attainment, employment status, and duration of symptoms.

Parent-reported multi-national study of the impact of congenital and childhood onset myotonic dystrophy.

Aim: The frequency and impact of symptoms experienced by patients with congenital, childhood, and juvenile-onset myotonic dystrophy (CDM/ChDM/JDM) is not documented. This report identifies symptomatic areas with the greatest disease burden in an international population of patients with early-onset myotonic dystrophy type-1 (DM1).

Method: We distributed surveys to parents of patients with CDM/ChDM/JDM.

Myotonic dystrophy health index: Correlations with clinical tests and patient function.

Introduction: The Myotonic Dystrophy Health Index (MDHI) is a disease-specific patient-reported outcome measure. Here, we examine the associations between the MDHI and other measures of disease burden in a cohort of individuals with myotonic dystrophy type-1 (DM1).

Methods: We conducted a cross-sectional study of 70 patients with DM1.

Quantifying cancer absolute risk and cancer mortality in the presence of competing events after a myotonic dystrophy diagnosis.

Recent studies show that patients with myotonic dystrophy (DM) have an increased risk of specific malignancies, but estimates of absolute cancer risk accounting for competing events are lacking. Using the Swedish Patient Registry, we identified 1,081 patients with an inpatient and/or outpatient diagnosis of DM between 1987 and 2007. Date and cause of death and date of cancer diagnosis were extracted from the Swedish Cause of Death and Cancer Registries.

A novel computerized functional assessment for human immunodeficiency virus-associated neurocognitive disorder.

Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) is present in 30-60 % of HIV-positive (HIV+) individuals and can be assessed by neuropsychological testing and level of functional impairment. HAND diagnosis therefore requires accurate assessment of functional impairment. The Computer Assessment of Mild Cognitive Impairment (CAMCI) is a computer-based screening tool that includes performance-based measures of functional impairment.

Splicing biomarkers of disease severity in myotonic dystrophy.

Objective: To develop RNA splicing biomarkers of disease severity and therapeutic response in myotonic dystrophy type 1 (DM1) and type 2 (DM2).

Methods: In a discovery cohort, we used microarrays to perform global analysis of alternative splicing in DM1 and DM2. The newly identified splicing changes were combined with previous data to create a panel of 50 putative splicing defects.

Diagnostic odyssey of patients with myotonic dystrophy.

The onset and symptoms of the myotonic dystrophies are diverse, complicating their diagnoses and limiting a comprehensive approach to their clinical care. This report analyzes the diagnostic delay (time from onset of first symptom to diagnosis) in a large sample of myotonic dystrophy (DM) patients enrolled in the US National Registry [679 DM type 1 (DM1) and 135 DM type 2 (DM2) patients]. Age of onset averaged 34.

Development of a genomic DNA reference material panel for myotonic dystrophy type 1 (DM1) genetic testing.

Myotonic dystrophy type 1 (DM1) is caused by expansion of a CTG triplet repeat in the 3' untranslated region of the DMPK gene that encodes a serine-threonine kinase. Patients with larger repeats tend to have a more severe phenotype. Clinical laboratories require reference and quality control materials for DM1 diagnostic and carrier genetic testing.

The impact of congenital and childhood myotonic dystrophy on quality of life: a qualitative study of associated symptoms.

This study systematically evaluated the symptoms associated with congenital and childhood myotonic dystrophy, and how these symptoms affect health related quality of life. We conducted interviews with patients affected by congenital or childhood myotonic dystrophy and their affected parent to identify which symptoms have the greatest effect on their lives. Each interview was recorded, coded, and analyzed using a qualitative framework technique.

A call for transparent reporting to optimize the predictive value of preclinical research.

The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the methodological reporting of animal studies in grant applications and publications. The main workshop recommendation is that at a minimum studies should report on sample-size estimation, whether and how animals were randomized, whether investigators were blind to the treatment, and the handling of data. We recognize that achieving a meaningful improvement in the quality of reporting will require a concerted effort by investigators, reviewers, funding agencies and journal editors.

Correlates of tumor development in patients with myotonic dystrophy.

Patients with myotonic dystrophy (DM) have recently been reported to be at increased risk of tumor development, but clinical associations related to this observation are unknown. We calculated the odds ratios (ORs) and 95 % confidence intervals (CI) of self-reported tumor development by patients' demographic and clinical characteristics to evaluate factors associated with tumor development in DM patients, using data from the National Registry of Myotonic Dystrophy and Facioscapulohumeral Dystrophy Patients and Family Members. Of the 911 participants, 47.

Cancer risk among patients with myotonic muscular dystrophy.

Context: Myotonic muscular dystrophy (MMD) is an autosomal-dominant multisystem neuromuscular disorder characterized by unstable nucleotide repeat expansions. Case reports have suggested that MMD patients may be at increased risk of malignancy, putative risks that have never been quantified.

Objective: To quantitatively evaluate cancer risk in patients with MMD, overall and by sex and age.