This project is supported by the Collagen VI Alliance, which is made up of Muscular Dystrophy UK, Cure CMD (USA), Muscular Dystrophy Ireland, AFM Telethon (France), Swiss Foundation for Research on Muscle Disease (FSRMM).
The global registry for collagen VI-related dystrophies is now LIVE! Click here for further information
Good progress has been made in the registry development; registry requirements are being assessed and the software available for holding the registry is being evaluated. There has been engagement with key stakeholders to understand the extent of data already stored for individuals with collagen VI-related myopathies.
32 new changes in the collagen VI genes (in 36 individuals) have been identified, which may cause myopathy. These will be submitted to mutation databases to aid future diagnosis of people with muscle wasting conditions.
In addition, 500 samples from individuals with undiagnosed limb girdle muscular dystrophy have been added to a biobank to be analysed by whole genome sequencing; this will identify the genetic mutations causing the individuals’ muscle wasting. Based on the group’s previous data, they expect around 18 of these 500 samples to contain mutations in collagen VI genes.
Once the registry has been developed, individuals identified through the whole genome sequencing work as having collagen VI mutations will be added to the register. Where possible, further biological samples will be taken from these individuals (e.g. serum and fibroblasts) and added to the biobank.
Further progress has been made in the development of the registry. A registry steering committee; which will help to make key decisions about the registry, has been formed. It consists of scientists who are experts in collagen VI related conditions and will also have representation from patient organisations and individuals with the conditions.
Appropriate, secure software has been identified and is being used to build the registry. It is important that the registry contains information that is useful to help inform clinical trial recruitment and natural history studies. To make sure that the necessary information is collected a set of questions to be included in the registry has been selected. This includes questions for patients to answer, as well as questions for doctors to enter additional clinical information. The questions are based on core data sets developed for other neuromuscular conditions but are tailored to capture the information which is most relevant to the collagen VI-related conditions.
Important documents, such as consent forms, information for those who sign up to the registry and clinicians and promotional material, are being designed and will be sent for ethical approval. Development of the registry website is underway.
Over the last 6 months, DNA samples have been collected from 185 people across Europe with an undiagnosed muscular wasting condition. These have been sent for exome sequencing, to identify the genetic mutation that causes the muscle wasting condition. Seven people were identified to have collagen VI-related dystrophies. Individuals with a new genetic diagnosis will now receive information about the registry from their clinician along with their sequencing results.
What are the aims of this project?
This project aims to develop important research tools that will support clinical trials for collagen VI-related conditions. These include:
- An improved and expanded registry for people living with collagen VI-related conditions worldwide.
Registries are databases that contain information about individuals affected by a particular condition. With permission, researchers and companies can access this information and identify patients that could take part in a study or clinical trial. As collagen VI-related conditions are very rare, recruitment for trials can be extremely challenging. This project will help to address this by improving European recruitment to the existing North American registry and expanding the registry to collect clinically verified information for collagen VI-related conditions.
- Outcome measures.
To carry out a clinical trial, researchers need to understand how conditions progress and have measures to monitor this progression. These measures are referred to as outcome measures, and are necessary to determine whether a drug or intervention is having an effect on a patient. This facilitate the development of imaging techniques such as Magnetic Resonance Imaging (MRI) as outcome measures for monitoring collagen VI-related conditions by finding a solution to collect and store MRI data with corresponding clinical information.
- Bio-banking.
A bio-bank is a collection of biological (usually patient) samples for use in research. This project will help to increase bio-banking by asking patients on the new global registry to donate blood and skin samples. These will be stored at the Newcastle Neuromuscular Biobank and will be accessible to international researchers investigating collagen VI-related conditions.
Why is this research important?
Although new treatments are being developed for collagen VI-related conditions, the translational environment to get these from the lab to patients is currently weak. This project will help to address this by developing resources that are important for research and clinical trials.
How will the outcomes of this research benefit people with collagen VI-related conditions?
This project will help to accelerate translational research and clinical trials for people with collagen VI-related conditions. Establishing a global registry will make it easier for companies to conduct trials in Europe and beyond, and could potentially increase the number of clinical trials taking place in the UK and other European countries. Facilitating the validation of MRI as an outcome measure could also have great value for patients as it is non-invasive and may reduce the need for muscle biopsies in future research and clinical practice.
How might this research impact on other neuromuscular conditions?
This project will facilitate the validation of MRI as an accurate method for examining muscle health. This knowledge could potentially be transferable to other neuromuscular conditions. This project will also attempt to integrate an existing patient faced registry with additional databases containing clinically verified data. This model for registry development could be applied to registries for other neuromuscular conditions.
Grant Information
Project leader: Professor Volker Straub
Institute: Newcastle University
Conditions: Ullrich congenital muscular dystrophy, Bethlem myopathy
Duration: Three years, starting 2016
Total cost (£): 193,929
Official title: Trial readiness for collagen VI myopathies
This research would not have been possible without individual donations, family fundraising activities, trusts and corporate support for our Ullrich CMD Appeal.
Donate now and help us ensure that effective treatments and expert care are available to all those living with collagen VI-related conditions, including Ullrich CMD. Thank you.