Published in 2018 is a consensus based approach for the myotonic dystrophy patient community. This gives general guidelines on how to approach, test and intervene in patients lives to achieve the most optimum outcomes.
Care-recommendations-for-adulats-with-Myotonic-Dystrophy
Special Focus on CRISPR: CRISPR on the moveSeptember 2017by Jeffrey Bouley | Email the authorEDIT CONNECTSHARING OPTIONS:
Special Focus: CRISPR Gene EditingCRISPR on the moveGene-editing technology continues to evolve In the relatively short time since gene editing involving clustered regularly interspaced short palindromic repeats (CRISPR) arrived on the life-sciences scene—most particularly in the handful of years since we got CRISPR/Cas9 and a much more simplified editing process—the technology has seen its ups and downs with regard to how safe, specific, efficient and reliable it is. But there is no doubt the technology continues to advance and almost certainly will hold a key position in the genomics arena for a long time to come. Germany’s Merck KGaA (not to be confused with U.S.-based Merck & Co.), for example, recently developed an alternative CRISPR genome editing method that it says makes CRISPR “more efficient, flexible and specific, giving researchers more experimental options and faster results that can accelerate drug development and access to new therapies.” Merck KGaA calls the new technique proxy-CRISPR and maintains that it provides access to previously unreachable areas of the genome. Most natural CRISPR systems, found in bacteria, cannot work in human cells without significant re-engineering, the company notes; however, proxy-CRISPR is said to provide a simpler and quicker method to increase their usability without the need to re-engineer native CRISPR proteins. “With more flexible and easy-to-use genome-editing technologies, there is greater potential in research, bioprocessing and novel treatment modalities,” said Udit Batra, a member of the company’s executive board and CEO of its Life Science unit. “As a leader in genome editing, Merck’s new technology is just one example of our commitment to solving challenges in the genome editing field, and we will continue to make CRISPR research a priority.” The company has filed several patent applications on the proxy-CRISPR technology, just one of several CRISPR patent application filings made by the company since 2012. Merck’s research on proxy-CRISPR, “Targeted Activation of Diverse CRISPR-Cas Systems for Mammalian Genome Editing via Proximal CRISPR Targeting,” was published in the April 7, 2017, edition of Nature Communications. The new technology is a follow-on to Merck’s existing CRISPR applications, and the company’s next suite of genome-editing tools for the research community—planned for launch later this year—is expected to include novel and modified versions of Cas and Cas-like proteins. More progress on the RNA front Researchers in the medical school at the University of California, San Diego (UC San Diego) in a 2016 study repurposed the CRISPR/Cas9 technique to track RNA in live cells in a method called RNA-targeting Cas9 (RCas9). In a new study, published Aug. 10 in Cell, the team took RCas9 a step further, using the technique to correct molecular mistakes that lead to microsatellite repeat expansion diseases, which include myotonic dystrophy types 1 and 2, the most common form of hereditary amyotrophic lateral sclerosis and Huntington’s disease. “This is exciting because we’re not only targeting the root cause of diseases for which there are no current therapies to delay progression, but we’ve re-engineered the CRISPR/Cas9 system in a way that’s feasible to deliver it to specific tissues via a viral vector,” said senior author Dr. Gene Yeo, professor of cellular and molecular medicine at UC San Diego School of Medicine. Microsatellite repeat expansion diseases arise because there are errant repeats in RNA sequences that are toxic to the cell, in part because they prevent production of crucial proteins. These repetitive RNAs accumulate in the nucleus or cytoplasm of cells, forming dense knots, called foci. In this proof-of-concept study, Yeo’s team used RCas9 to eliminate the problem-causing RNAs associated with microsatellite repeat expansion diseases in patient-derived cells and cellular models of the diseases in the laboratory. There is still a ways to go before RCas9 could be tested in patients, though, Yeo acknowledged. One bottleneck is efficient delivery of RCas9 to patient cells, as the non-infectious adeno-associated viruses that are commonly used in gene therapy are typically too small to hold Cas9 to target DNA. Yeo’s team made a smaller version of Cas9 by deleting regions of the protein that were necessary for DNA cleavage, but dispensable for binding RNA. “The main thing we don’t know yet is whether or not the viral vectors that deliver RCas9 to cells would illicit an immune response,” he said. “Before this could be tested in humans, we would need to test it in animal models, determine potential toxicities and evaluate long-term exposure.”
There is no treatment for myotonic dystrophy…yet. In the interim period a new study shows that behaorial therapy and exercise can help to stem the huge impact this disease has on patients. Here is the conclusion :
Interpretation Cognitive behavioural therapy increased the capacity for activity and social participation in patients with myotonic dystrophy type 1 at 10 months. With no curative treatment and few symptomatic treatments, cognitive behavioural therapy could be considered for use in severely fatigued patients with myotonic dystrophy type 1.
However, in reviewing the study this approach requires huge amount of medical resources that may not be available. Hours of analysis of the issues with patients and then tailoring the approach to each patient and tweaking it periodically. Working with a medical professionals for hours is very expensive and most health systems ahve no way to accomplish this.
Cognitive behavioural therapy with optional graded
exercise therapy in patients with severe fatigue with myotonic
dystrophy type 1: a multicentre, single-blind, randomised trial
Kees Okkersen, Cecilia Jimenez-Moreno, Stephan Wenninger, Ferroudja Daidj, Jeffrey Glennon, Sarah Cumming, Roberta Littleford,
Darren G Monckton, Hanns Lochmüller, Michael Catt, Catharina G Faber, Adrian Hapca, Peter T Donnan, Gráinne Gorman, Guillaume Bassez,
Benedikt Schoser, Hans Knoop, Shaun Treweek, Baziel G M van Engelen, for the OPTIMISTIC consortium†
Summary
Background Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults and leads to severe fatigue, substantial physical functional impairment, and restricted social participation. In this study, we aimed to
determine whether cognitive behavioural therapy optionally combined with graded exercise compared with standard care alone improved the health status of patients with myotonic dystrophy type 1.
Methods We did a multicentre, single-blind, randomised trial, at four neuromuscular referral centres with experience in treating patients with myotonic dystrophy type 1 located in Paris (France), Munich (Germany), Nijmegen (Netherlands), and Newcastle (UK). Eligible participants were patients aged 18 years and older with a confirmed
genetic diagnosis of myotonic dystrophy type 1, who were severely fatigued (ie, a score of ≥35 on the checklistindividual strength, subscale fatigue). We randomly assigned participants (1:1) to either cognitive behavioural therapy plus standard care and optional graded exercise or standard care alone. Randomisation was done via a central webbased system, stratified by study site. Cognitive behavioural therapy focused on addressing reduced patient initiative, increasing physical activity, optimising social interaction, regulating sleep–wake patterns, coping with pain, and
addressing beliefs about fatigue and myotonic dystrophy type 1. Cognitive behavioural therapy was delivered over a 10-month period in 10–14 sessions. A graded exercise module could be added to cognitive behavioural therapy in Nijmegen and Newcastle. The primary outcome was the 10-month change from baseline in scores on the DM1-Activ-c scale, a measure of capacity for activity and social participation (score range 0–100). Statistical analysis of the primary outcome included all participants for whom data were available, using mixed-effects linear regression models with
baseline scores as a covariate. Safety data were presented as descriptives
This trial is registered with ClinicalTrials. gov, number NCT02118779.
Findings Between April 2, 2014, and May 29, 2015, we randomly assigned 255 patients to treatment: 128 to cognitive behavioural therapy plus standard care and 127 to standard care alone. 33 (26%) of 128 assigned to cognitive behavioural therapy also received the graded exercise module. Follow-up continued until Oct 17, 2016. The DM1- Activ-c score increased from a mean (SD) of 61·22 (17·35) points at baseline to 63·92 (17·41) at month 10 in the cognitive behavioural therapy group (adjusted mean difference 1·53, 95% CI –0·14 to 3·20), and decreased from 63·00 (17·35) to 60·79 (18·49) in the standard care group (–2·02, –4·02 to –0·01), with a mean difference between groups of 3·27 points (95% CI 0·93 to 5·62, p=0·007). 244 adverse events occurred in 65 (51%) patients in the cognitive behavioural therapy group and 155 in 63 (50%) patients in the standard care alone group, the most common
of which were falls (155 events in 40 [31%] patients in the cognitive behavioural therapy group and 71 in 33 [26%] patients in the standard care alone group). 24 serious adverse events were recorded in 19 (15%) patients in the cognitive
behavioural therapy group and 23 in 15 (12%) patients in the standard care alone group, the most common of which were gastrointestinal and cardiac. Interpretation Cognitive behavioural therapy increased the capacity for activity and social participation in patients with myotonic dystrophy type 1 at 10 months. With no curative treatment and few symptomatic treatments, cognitive behavioural therapy could be considered for use in severely fatigued patients with myotonic dystrophy type 1.
This is a paper that is the sesult of a meeting of doctors in Spain and a consortium of ideas on how to diagnosis myotonic dystrophy. It is in Spanish
Clinical-Guide-to-disagnosing-Myotonic-dystrophyThis is a comprehensive survey of the Myotonic Dystrophy Population. Its very interesting for me personally as my Sons name is Christopher and he was born in the Midwest. Recently the Report was mailed to interested parties and there is a link to the Full report at the very end of the report. I would recommend that you fill out the form and the receive the full report. There are some data summaries and survey samples in this post as well. Over 4,000 surveys were sent out to a randomized group of contacts on patient organization and others mailing list. Over 1000 were returned. Here is some summary information about the report.
The Christopher Project is a collaborative research project between national patient advocacy organizations, healthcare providers, and patients and families in the USA and Canada. It was designed to complement existing research by directly surveying patients and their family members/caregivers about their experience living with myotonic dystrophy.
To accomplish this, a large survey was distributed to patients in the summer of 2014 and a follow-up survey was distributed to family members/caregivers in early 2015. This Data Supplement is a summary of all of the responses to the questions asked on both surveys, presented as ‘frequency tables’ (i.e., how ‘frequently’ each answer appeared).
This Data Supplement is a companion to the main Christopher Project Report to the Myotonic Dystrophy Community, which can be found online at: www.christopherproject.org.
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