Myotubular and Centronuclear Myopathy Patient Registry update

The Myotubular and Centronuclear Myopathy (MTM and CNM) Patient Registry is an international, patient-reported database created to capture clinical and genetic data from patients who have been diagnosed with these ultra-rare genetic conditions and on female carriers of x-linked myotubular myopathy. The registry was established in March 2013 by the Myotubular Trust in collaboration with TREAT-NMD (an international neuromuscular network of clinicians and specialist centres) and other key opinion leaders, and was transferred to the John Walton Muscular Dystrophy Research Centre at Newcastle University in 2015.  Below Lindsay Murphy provides a Patient Registry update.

Information in the registry is collected through a secure online portal, directly from the participants (or from a parent or guardian if the patient is under 18). We also welcome registration of deceased patients, if their family wishes to contribute their data. Online registration is available to all of these groups and can be done in English, German, Spanish, Polish, Italian or French. The main purpose of the registry is to aid the rapid identification of eligible patients for clinical studies when approached by researchers and pharmaceutical companies. The registry also disseminates disease-relevant information to participants; provides a source of information to academics, industry and healthcare professionals to support research and the development of standards of care; and seeks to provide support to the MTM and CNM community. To give a snapshot of some of the information held within the registry, a few current data items are presented below.

To date, a total of 249 participants are registered with the MTM and CNM Patient Registry. Participants have registered from across Africa, Europe, Asia, the Americas and Oceania, reflecting the registry’s truly global nature (see Figure 1).

Map showing number of consented registrations by country.

Figure 1: Number of consented registrations by country

The age range of registry participants is from 0 to 74 years, and of those registered, 71.1% are patients, 11.9% are deceased patients and 10.9% are female carriers of the XLMTM gene.

The registry captures both the patient-reported medical diagnosis and the genetic diagnosis. A doctor will review a patient’s symptoms and perform tests to reach a medical diagnosis. Among the muscular dystrophies, symptoms may be very similar, therefore, to be certain of the cause of illness, it is important to have a genetic test. This will identify if a change or mutation in a specific gene is present and will provide a genetic diagnosis of a patient’s condition. If a patient wishes to participate in clinical trials it is of great importance to obtain a genetic diagnosis as this if often a specific requirement of trial coordinators.

Information captured by the registry on medical diagnosis illustrates that most living registry participants have MTM (65.3%), with the remaining participants having CNM (28.6%) or either an unconfirmed or ‘other’ diagnosis (6.2%, see Figure 2).

Pie chart showing medical diagnoses of living registry patients.

Figure 2: Medical diagnoses of living registry patients

The genes associated with the conditions MTM and CNM in living patients are presented in Figure 3. Mutations within the X-linked MTM gene are most commonly associated with a medical diagnosis of MTM. In comparison, the genetic causes of CNM are attributed to a wider number of genes, most notably dynamin 2 (DNM2) and skeletal muscular ryanodine receptor (RYR1).

Chart showing Living registry patients by gene mutation, stratified by diagnosis.

Figure 3: Living registry patients by gene mutation, stratified by diagnosis

Recruitment to clinical trials and research studies is one of the main purposes of the registry, and has proven to be highly successful. Participants have been informed of, and recruited to, a number of such studies, including:

  • Natural History Study of MTM patients at the Institute of Myology
  • ‘INCEPTUS: A Clinical Assessment Study in X-Linked Myotubular Myopathy’, carried out by Audentes Therapeutics
  • Genetic Alliance Survey about preimplantation genetic diagnosis for CNM patients with a variant in the DNM2 gene
  • ‘Journeying: a research project exploring the experiences of power wheelchair users in the built environment and on public transport’.

The registry has also helped support the promotion of surveys and studies, including a long-term ventilation survey for patients and their carers and an academic research study investigating physical activity in patients with various neuromuscular conditions.

The MTM and CNM Patient Registry is a highly successful venture for participants, clinicians and academics alike, however, there is always room for improvement. With that in mind, we are hoping to add the ability for doctors to contribute clinical data from their consenting patients, which may help to address the patient language barrier and issues related to internet access. Also, clinician verification of patient-entered data will help to assure data quality.

Further information

For further information about the MTM and CNM Patient Registry, please visit the registry website.

 

MTM and CNM Patient Registry

This article first appeared in the Information Point newsletter Our World in 2018, when Jo Bullivant, curator of the MTM-CNM Patient Registry wrote about the registry.

Have you registered in the Myotubular and Centronuclear Myopathy (MTM and CNM) Patient Registry yet? The MTM and CNM Patient Registry is an international registry open to MTM or CNM patients and female carriers of x-linked myotubular myopathy (XLMTM). It is funded by the Myotubular Trust and Muscular Dystrophy UK and managed by the John Walton Muscular Dystrophy Research Centre at Newcastle University, as part of the TREAT-NMD Alliance.

There are many reasons why patient registries are so important in rare diseases, including:

  • they provide doctors with information about the conditions, to help improve standards of care
  • they support and encourage research by providing (anonymous) data about the conditions
  • being part of a registry means that researchers or pharmaceutical companies can ask the Registry Curator to let participants know if there is a trial or research study that they might be eligible for
  • pharmaceutical companies and other organisations are increasingly acknowledging the value of real-world, patient-reported data, as it can potentially reduce the need for placebo arms in clinical trials and help to develop patient-centred outcome measures.

Being part of a registry will also mean that researchers or pharmaceutical companies can ask the Registry Curator to let you know if there is a trial or research study coming up that you might be eligible for.

Further information

Learn more about the Myotubular and Centronuclear Myopathy Patient Registry

To learn more about the Patient Registry and to register online, visit the website or email Jo Bullivant, the Registry Curator with any questions.

Clinical trials

Information about clinical trials can also be found on Patient Registry website.

Real world data in clinical trials

If you would like to find out more about the use of real world data in clinical trials, take a look at the article from Muscular Dystrophy News below.

An update on The Myotubular and Centronuclear Myopathy (MTM and CNM) Patient Registry

This story first appeared in the Information Point newsletter Our World in 2017 when Jo Bullivant,the Registry Curator for the Myotubular and Centronuclear Myopathy Patient Registry wrote about the registry. You can also read about the registry in the article below.

Being part of a patient registry, particularly for a rare disease, provides crucial data to scientists and researchers who are working to improve understanding of your condition and to develop treatments. It also means that you are more easily contactable in case there are any research studies or trials that you might be interested in or eligible for.

The MTM and CNM Patient Registry is funded by the Myotubular Trust and managed by Newcastle University as part of the TREAT-NMD Neuromuscular Network.

Numbers in the registry are building all the time. The image below shows registration numbers as they were on 24 February 2017.

 

Patient registry numbers as at 24 February 2017.

 

For those who have already joined, here are some very important reminders.

  • If you have started a registration but have not yet provided your consent or completed the online questionnaire, please do this as soon as possible.
  • If you have completed your registration but have not logged in since 2 May 2017, please log in again and complete the updated consent information.
  • If you have registered but have not yet provided a copy of your genetic report, please upload it into the registry so we can validate your data.
  • You can go directly to the log in page at https://mtm.ccgapps.com.au/rdrf/mtm, Your username is the email address you used to register (and is case-sensitive) – if you have forgotten your password there is a link on the log-in page for you to re-set it.

For our European friends

The online registry, plus the information and consent pages, are now available in German (it will automatically detect the language setting of your browser) and other languages to follow soon are Spanish, Polish, Italian and French.

If you have any questions you are welcome to contact me at mtmcnmregistry@treat-nmd.eu. I’m always happy to help. Thank you for your interest in the registry – I look forward to hearing from you soon.

Further information

If you have not registered yet, you can find out more about the registry and join online at the Patient Registry website.

The Myotubular and Centronuclear Myopathy Patient Registry logo.