Research Opportunity in Florida

You can assist researchers on a couple of issues in myotonic dystrophy. Read more about this ongoing study. (Posted in May 2019)

Studies of skeletal muscle and gastrointestinal dysfunction in myotonic dystrophy and controls

Purpose

This study is designed to obtain data regarding 2 aspects of the phenotype in myotonic dystrophy (dystrophia myotonica or DM). These are multi-system diseases leading to symptoms in many regions of the body including skeletal muscles, central nervous system and the GI tract.

The aims of the study are two-fold: 1. to obtain physiological recordings of muscle contraction and motor unit activation in selected skeletal muscles to obtain possible outcome measures for future drug trials as well as understand the physiological underpinnings of motor dysfunction in these patients; 2. to study the role of the gut microbiome in relation to the gastro-intestinal dysfunction in DM patients.

Procedures 

  • Tasks to measure strength, fatigue, force and reaction time
  • Blood and stool samples 

For more details about study procedures, please contact Stephen Gullet:

Eligibility 

  • Over the age of 18
  • Molecularly confirmed DM 1 or DM 2 (symptomatic subjects in whom diagnosis is based on DNA analysis in affected family members will also qualify)
  • Ambulatory with or without assistive devices
  • Competent and willing to provide informed consent and participate in study procedures

Additional criteria apply, for more information please contact Stephen Gullet:

Age

18 to 65
65 and over

Gender

Male
Female

Can be done from home

No

Keywords

Muscular dystrophyMuscular dystrophy – resources, Neurology

Principal Investigator

S.H. Subramony, MD

Department

Neurology

Contact Information

stephen.gullett@neurology.ufl.edu

352-273-6003

Genetic Testing best practices for Myotonic Dystrophy Patients

Because of the disease characteristics in DM1 and DM2, appropriate molecular testing and reporting is very important for the optimal counseling in myotonic dystrophy. Here, we describe best practice guidelinesfor clinical molecular genetic analysis and reporting in DM1 and DM2, including presymptomatic and prenatal testing.

Maximum Voluntary Ventilation can help predict lung issues in Myotonic Dystrophy patients

A new study of myotonic dystrophy patients indicates that an older style test of maximum voluntary ventilation may help Myotonic Dystrophy patients know their lung function better. 

The maximal voluntary ventilation (MVV) is another measure of the neuromuscular and respiratory systems. The MVV is the total volume of air exhaled during 12 sec of rapid, deep breathing, which can be compared with a predicted MVV defined as the forced expiratory volume in 1 sec (FEV1× 35 or 40. A significant difference between the predicted and measured MVV may indicate insufficient neuromuscular reserve, abnormal respiratory mechanics, or an inadequate effort. Progressive reduction of tidal volumes during the test is consistent with neuromuscular abnormalities but also occurs with gas trapping as a result of disorders that cause airflow limitation.

Clinical_implication_of_maximal_voluntary.-ventilation-in-Myotonic-Dystrophy

Potential Myotonic Dystrophy Drug Fails! – Ionis Myotonic Dystrophy Drug fails to reach minimal therapeutic value

In a instant news email the Myotonic Dystrophy Foundation (MDF) released information that the Ionis Pharmaceutical Drug DMPK-2.5Rx research project has been canceled. The drug DMPK-2.5Rx did not work, and did not get the correct amount of therapeutic drugs into the cells of the patients with myotonic dystrophy. The company may still continue research on a more potent combination but the current trial is halted.

This is hard to hear news for the myotonic community. This is the second drug in development to fail. This new drug is part of a number of new generation of interest drugs  in trying to find a drug to treat the disease. There are still a number of drugs in development but the Ionis one was the most advanced. Perhaps the information in this trial will be of help to the other drugs in development.  For those in the late stages of the disease the length of time to find a treatment that is FDA approved in unlikely now.

There continues to be some “off label” treatments including erythromycin and some NSAIDS as well as Actinomycin-D but none have had any proven human effect.

More information below.

Ionis Pharmaceuticals Reports on
DMPKRx Phase 1/2 Clinical Trial

Ionis Pharmaceuticals recently concluded a Phase 1/2 clinical trial to evaluate IONIS-DMPK-2.5Rx in myotonic dystrophy patients. IONIS-DMPK-2.5Rx was designed to target the toxic DMPK RNA in muscle that is responsible for myotonia or muscle dysfunction in DM1 patients. The clinical trial used dose escalation to assess safety and explore biomarkers for target engagement in muscle biopsies.

Ionis reports that small but encouraging trends in biomarker and splicing changes were observed during the trial, and that this study provided a much better understanding of how future clinical trials and improved clinical endpoints may be used. However, drug levels measured in biopsy tissue from trial participants indicated that the amount of target engagement would not achieve the desired therapeutic benefit to treat this disease.

Without the desired drug levels in muscle, Ionis has decided not to advance IONIS-DMPK-2.5Rx. It will instead pursue the discovery of a more potent drug to target DMPK using new muscle-targeting LICA chemistry made at Ionis.

The company sincerely thanks everyone in the DM community that participated in the study – patients, caregivers and physicians, noting, “we are committed to the DM patient community and we hope to advance a new, more potent drug into development that will benefit people living with DM1.”

Ionis invites DM community members to submit questions regarding the above announcement via this email address. MDF will collect questions through January 12th and then work with Ionis to get answers out to the community as soon as possible.

Study of Childhood and Congenital Myotonic Dystrophy

Here is a recent study of issues with congenital and childhood myotonic dystrophy. It seems pretty comprehensive and has a lot of good information. The summary is below followed by the link to the full study. The study does not also provide information on the link to autism or autism spectrum disorders that many of the children have. The study does not go into depth on the adult form of the disease that follows as the children age and go through puberty. But a good basic review.

“In neonates and children, DM1 predominantly affects muscle strength, cognition, respiratory, central nervous and gastrointestinal systems. Sleep disorders are often under recognized yet a significant morbidity. No effective disease modifying treatment is currently available and neonates and children with DM1 may experience severe physical and intellectual disability, which may be life limiting in the most severe forms. Management is currently supportive, incorporating regular surveillance and treatment of manifestations. Novel therapies, which target the gene and the pathogenic mechanism of abnormal splicing are emerging. Genetic counseling is critical in this autosomal dominant genetic disease with variable penetrance and potential maternal anticipation,as is assisting with family planning and undertakingcascade testing to instigate health surveillance in affected family members.”

BELOW click on hyperlink for full study in PDF form.

Childhood Myotonic dystrophy 2015