Other AIMS of OPTIMISTIC

OPTIMISTIC will look at many aspects of myotonic dystrophy in order to better understand the condition and to improve care and management internationally.

OPTIMISTIC hopes to better prepare the field for future clinical trials and investigations; working towards clinical trial readiness for DM1 across Europe.

Working alongside the main trial, teams within OPTIMISTIC will also be looking at:

  • Improving cardiac screening methods for DM1.
  • Better understanding the genetic causes of DM1 and how it affects people differently.
  • Identifying and validating biomarkers using the latest bioinformatic techniques.
  • Establishing and validating outcome measures for clinical trials.

Cardiac Screening

Abnormal heart rhythm (e.g. heart block) is often seen as a symptom of DM1. The exact cause of this arrhythmia has been the subject of much research and it is thought to be myocardial fibrosis. This is when there is a problem with the heart’s muscle cells which causes hardening or scarring of heart tissue. Heart muscle cells (myocytes) are replaced with tissue that cannot contract properly and this stops the heart from beating regularly.
These cardiac complications are serious and can lead in most severe cases to the death of the person affected. Currently there are no agreed recommendations on when, how often or to what extent people with DM1 should be monitored for heart abnormalities by their doctors.

OPTIMISTIC aims to:

  • Establish procedures that can be used to screen and monitor cardiac function in DM1 patients effectively.
  • Use state of the art magnetic resonance technologies to observe the cardiac changes in people with DM1.

Genetics

DM1 is caused by an expansion of DNA: this means that a specific triplet sequence is repeated too many times in the DMPK gene.  The varying severity in people with DM1 can be explained through genetic diagnosis; For example the greater the size of the expansion (or repeat number) the more severe the symptoms are.  In addition, the size of the DNA expansion increases with age making it hard to assess how the disease will progress.  The severity of the disease can be best determined by the expansion size at the onset of the disease.

OPTIMISTIC will use genetic analysis to:

  • Work towards a prognostic tool that can estimate the DNA expansion size at birth.
  • Identify patients carrying varying repeats within the DNA expansion.
  • Assess the relationship between the size of the DNA repeat, age of onset of the disease and severity of disease.
  • Increase understanding of the genetic mechanism of DM1 and how this relates to the phenotype.

Biomarkers

Biomarkers are substances in the body that can be used as an indicator of disease. They can be used to help doctors diagnose a disease and monitor how it is progressing. Biomarkers can also be used to see how well the body responds to a treatment.  At this time new and exciting therapeutic treatments are emerging for DM1 and it is important to have reliable biomarkers in place for use in well designed and thorough clinical trials.

Molecules that can act as biomarkers can be different types of protein and RNA. These can both be found in blood and urine so samples can easily be obtained and analysed.

OPTIMISTIC aims to:

  • Analyse blood and urine samples to find and validate biomarkers in DM1.
  • Use magnetic resonance to find and evaluate biomarkers in muscles.
  • Use bioinformatics tools to compare biomarkers with other neuromuscular disorders.

Outcome measures

Outcome measures are the tests used to decide whether a treatment being tested in a trial is having any effect. Using the right outcome measure is vital to making sure a trial can accurately assess whether or not a treatment works. They can be a physical test for example how far someone can walk or a biological indicator (biomarker) for example a specific molecule in the blood. The varied and complex nature of the condition increases the challenge in validating outcome measures for DM1.

The main aims of this part of OPTIMISTIC are:

  • Assess the effect of cognitive behavioural therapy and exercise in DM1 using appropriate outcome measures.
  • Establish and validate outcome measures that can be used for clinical trials in the future.

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