Research News
4.10.12 New, Groundbreaking Research Grant Funded by Myotubular Trust Offers A Huge Leap Forward In Understanding MTM And CNM Helping Find Potential New Therapeutic Treatments

The Myotubular Trust is delighted to announce a fourth successive year of making substantial research grants to help find a treatment or cure for myotubular and centronuclear myopathy. Following a rigorous application and peer review process, our Scientific Advisory Board recommended that this year's grant goes to a joint team of Dr Heinz Jungbluth at King's College, London, UK and Dr Susan Treves who heads the Muscle Research group at Basel University Hospital, Switzerland.

Although a lot of work has been done in identifying the genes that cause myotubular and centronuclear myopathy, the precise way in which those genetic faults cause muscle weakness, and other complications, is just not understood. To understand this 'why' will be a huge step in developing a cure or treatment.

Recent research findings have suggested two very promising lines of further investigation that may tell us something fundamental about these conditions, and Drs Jungbluth and Treves will investigate them both. The first is the link between myotubular and centronuclear myopathy and the processes that cause muscles to contract, in particular the process of releasing calcium into muscle cells. The second is a link between the "recycling" mechanism in cells and certain genes that cause myotubular and centronuclear myopathy. You can read more about the research here.

We are delighted to be funding these very exciting lines of investigation, being carried out by this very impressive team of researchers.



20.9.12 Myotubular Trust Announces A Fifth Call To Grant Application

We are delighted to announce a Fifth Call to Application. We are looking to fund further projects that will help find a cure and/or a treatment for any of the three types of myotubular myopathy (congenital X-linked recessive; congenital autosomal recessive; autosomal dominant), focusing on research that would not generally be funded by public or industrial funding sources. Our Fifth Call will be open to research bodies internationally.

To date, we have awarded six research grants / fellowships for the following projects:

  • Gene therapy for x-linked myotubular myopathy and pathophysiology – Dr Anna Buj Bello, Genethon, Evry
  • Membrane trafficking and T tubule structure and function in a canine model of centronuclear myopathies – Dr Richard Piercy, Royal Veterinary College, London
  • Deciphering the molecular pathway involving centronuclear myopathy genes – Manuela D’Alessandro, IGBMC, Illkirch
  • Gene therapy for autosomal dominant centronuclear myopathy by Transplicing – Dr Marc Bitoun, INSERM, Paris
  • Next generation sequencing to tackle centronuclear myopathies – Dr Jocelyn Laporte, IGBMC, France
  • Secondary pathogenic mechanisms in XLMTM and CNM – Dr Susan Treves, Basel University Hospital, Basel and Dr Heinz Jungbluth, King’s College London

In particular we would like to encourage the application of new technologies to research into myotubular myopathy, which may involve collaboration between different medical disciplines and / or different research institutions. We are also willing to consider applications which involve joint funding with other organisations.

Please see our Research Programme & Grants Information Page to read more and download an application form.



12.07.12 New Research Leads To Better Detection And Diagnosis Of MTM1 In Rare Cases Where No Genetic Mutation Has Been Found

Dr Heinz Jungbluth reports:

'Mutations in the MTM1 gene are the only known genetic cause of the X-linked form of centronuclear (myotubular) myopathy but in a proportion of typically affected boys the underlying genetic defect remains elusive despite extensive investigations. Whilst some of these boys will have mutations in recently identified CNM genes - DNM2, RYR1 and BIN1 - associated with other modes of inheritance, research groups in France and the United Kingdom have now independently identified rare faults concerning the MTM1 gene which may not be detectable on routine genetic testing but will be picked up with more sophisticated techniques available in specialist laboratories. Identification of these rare faults in the MTM1 gene will help and enable counselling for families who so far have not had a precise genetic diagnosis'.

X-linked myotubular myopathy due to a complex rearrangement involving a duplication of MTM1 exon 10
Trump N, Cullup T, Verheij JB, Manzur A, Muntoni F, Abbs S, Jungbluth H.
Neuromuscul Disord. 2012 May;22(5):384-8. Epub 2011 Dec 9.

Another related article from the laboratory of Dr Jocelyn Laporte in France may also be of interest

Novel molecular diagnostic approaches for X-linked centronuclear (myotubular) myopathy reveal intronic mutations.
Tosch V, Vasli N, Kretz C, Nicot AS, Gasnier C, Dondaine N, Oriot D, Barth M, Puissant H, Romero NB, Bönnemann CG, Heller B, Duval G, Biancalana V, Laporte J.
Neuromuscul Disord. 2010 Jun;20(6):375-81.

In summary, while Dr Heinz Jungbluth's and Dr Stephen Abb's DNA Laboratory at Guy's and St Thomas' Hospital does routinely test for such changes in MTM1 sequencing negative patients with characteristic features, this is something parents of a child with MTM/CNM but no confirmed mutation ought to consider checking and discussing further with their geneticist or neuromuscular specialist. It is also important to emphasize that these unusual defects in the MTM1 gene are likely to be very rare indeed, and that it is probably as likely that a child with MTM1/CNM without confirmed genetic defect has a mutation in another, probably currently unknown gene.



11.06.12 New Hope For Treating Patients With X-Linked Myotubular Myopathy: Proof of Concept Support For Future Clinical Trials in XLMTM Patients

Myotubular Trust are delighted to share with you the exciting pre-publication news reported by researcher, Dr Anna Buj-Bello, following the research work which was funded by us.

Dr Anna-Buj Bello reports:

     "From 2009 to 2011, Myotubular Trust has supported our team at Genethon to develop therapeutic strategies for myotubular myopathy based on gene therapy. The main aim of this project was to introduce the normal MTM1 gene into muscle cells from the mouse models of the disease. In order to achieve that, we constructed a genetically modified viral vector that carries the MTM1 gene. Administration of this vector to mutant mice leads to the presence of the MTM1 protein in muscles of the body and correction of the severe muscle pathology in these animals. These results are very encouraging and provide proof-of-concept support for future clinical trials in x-linked myotubular myopathy (XLMTM) patients."

    "In addition, since it is known that patients with XLMTM have muscle cells which are smaller than normal, our team has been working on other studies that involve the use of growth factors. Growth factors are molecules that make our cells increase both in number and in size. To test the therapeutic efficacy of a growth factor called insulin-like growth factor-1, or IGF-1 for short, and an inhibitor of myostatin in mice with myotubular myopathy, we have produced the vectors for gene transfer and experiments are currently ongoing in the laboratory." Dr Anna Buj-Bello.

You can read more about the Myotubular Trust funded research that led to this proof of concept support for future clinical trials in XLMTM patients here.

Myotubular Trust visits Dr Anna Buj-Bello and her team at Généthon, November 2011



11.06.12 Myotubular Myopathy And The Neuromuscular Junction: A Novel Approach

"Thanks to Myotubular Trust support we have been able to participate in international collaborative projects, such as a study that shows alterations in the junctions between muscle fibers and nerve terminals in mice and evaluates the use of an acethylcholinesterase inhibitor as a therapeutic agent." Dr Anna Buj-Bello, Généthon, INSERM, Evry, France

Myotubular myopathy and the neuromuscular junction: a novel therapeutic approach from mouse models.   Dowling JJ, Joubert R, Low SE, Durban AN, Messaddeq N, Li X, Dulin-Smith AN, Snyder AD, Marshall ML, Marshall JT, Beggs AH, Buj-Bello A, Pierson CR.   Dis Model Mech . 2012 May 24. [Epub ahead of print] (pdf) Full Article



15.9.11 Myotubular Trust Announces A Fourth Call To Grant Application

We are delighted to announce a fourth Call to Application. We are looking to fund further projects that will help find a cure and/or a treatment for any of the three types of myotubular myopathy (congenital X-linked recessive; congenital autosomal recessive; autosomal dominant), focusing on research that would not generally be funded by public or industrial funding sources. Our fourth Call will be open to research bodies internationally.

To date, we have awarded research grants / fellowships for the following projects:

  • Gene therapy for x-linked myotubular myopathy and pathophysiology – Dr Anna Buj Bello, Genethon, Evry (read more here)
  • Membrane trafficking and T tubule structure and function in a canine model of centronuclear myopathies – Dr Richard Piercy, Royal Veterinary College, London (read more here)
  • Deciphering the molecular pathway involving centronuclear myopathy genes – Manuela D’Alessandro, IGBMC, Illkirch (read more here)
  • Gene therapy for autosomal dominant centronuclear myopathy by Transplicing – Dr Marc Bitoun, INSERM, Paris (read more here)
  • Next generation sequencing to tackle centronuclear myopathies – Dr Jocelyn Laporte, IGBMC, France (read more here)

In particular we would like to encourage the application of new technologies to research into myotubular myopathy, which may involve collaboration between different medical disciplines and / or different research institutions. We are also willing to consider applications which involve joint funding with other organisations.

Please see our Research Programme & Grants Information Page to read more and download an application form.



19.8.11 Two Further Research Grants Funded by Myotubular Trust in 2011

The Myotubular Trust is delighted to announce two new research grants which will make a fundamental contribution to our understanding of the condition and help us in our quest to find a cure.

The first will be run by Dr Jocelyn Laporte at the world renowned IGBMC laboratory in France (where the mtm1 gene was discovered in 1996.) They will use next generation gene sequencing technology to carry out 'high throughput' gene analysis, which it is hoped will lead to the discovery of the missing genes which cause centronuclear and myotubular myopathy. Finding these 'other' genes is important for two critical reasons - it will provide much better information for families about the gene that affects them, and should shed light on new drugs as possible therapeutic options. Read the Lay Summary of the research by Dr Jocelyn Laporte here.

The second project will be be led by Dr Marc Bitoun at INSERM in Paris where they will evaluate a new gene therapy technique as a possible cure for centronuclear myopathy. They will use trans-splicing to 'cut and paste' a working gene onto the faulty gene for dynamin 2 (one of the three genes currently implicated as a cause of cnm), and will carry the working gene using a virus as a vectors . This new gene therapy technology is a very exciting possible route to a cure as the 'reprogrammed' gene is under the direct control of the patient's cells, and therefore less likely to be rejected by the body. Read the Lay Summary of the research by Dr Marc Bitoun here.



29.7.11 Calling All Patients Who Don't Have A Genetic Diagnosis For MTM/CNM.

Title of study : Next generation sequencing to identify novel genes implicated in centronuclear myopathies and other congenital myopathies

Purpose of Study: For any disease or condition and including the Myotubular and Centronuclear Myopathies, the identification of the mutation is the most important first step for genetic counseling and therapies. Over recent years, there has been a discovery of several genes causing Myotubular and Centronuclear Myopathy, including MTM1, DNM2, BIN, however, the causative mutations in half of patients are still unknown.

This project, funded by Myotubular Trust, uses a new "high-throughput" gene sequencing approach and aims to help patients who have not been able to find out which genes have caused their form of centronuclear myopathy to identify the exact mutation.

The project, which will be run by Dr Jocelyn Laporte, Dr Johann Böhm and colleagues in the department of Translational Medicine at IGBMC in France, will use next generation sequencing to identify novel genes implicated in centronuclear myopathies.

Knowing the exact mutation has many benefits, including the first step to providing accurate genetic counseling, to improve health care and disease management and to identify novel drug targets that may be more accessible for therapeutic development. This knowledge is often required for the inclusion into specific clinical trials.

Because the patient testing will form part of this important research project, it is being offered free of charge for any patient who wishes to find out their mutation, but on the basis that the researchers cannot guarantee a positive result or time frame.

So to summarize:

  • The analysis is free of charge for the patients as it is on a research basis
  • They do not guarantee a positive result or a time frame
  • As they analyze all genes, they may find gene variations associated with additional medical conditions (that have nothing to do with the muscle disease). The patients will be informed about these gene variations only in case of a direct benefit for the patient and based on current medical knowledge.

Eligibility (Inclusion/Exclusion criteria) People who have a diagnosis of centronuclear myopathy and have no confirmed genetic diagnosis are candidates to participate in this study. The analysis is proposed to patients for whom mutations in known genes has been excluded.

Travel Arrangements: No direct travel is necessary. Sending in a DNA sample is required. Contact the investigator for a collection kit and details.

Contact Information:

Dr. Johann Böhm
IGBMC
1, Rue Laurent Fries
67404 Illkirch
France

johann@igbmc.fr

Phone : 33 (0)388653415 (office)

Download a Consent Form (in pdf) or Consent Form (in word doc)



10.7.11 Myotubular Trust European Family Conference, London

"How come I don't feel so alone any more? Simple - I met so many wonderful professionals, families and friends yesterday at the Myotubular Trust European Conference in London." Read more about our 2011 Family Conference.



7.10.10 Myotubular Trust Announces A Third Call To Grant Application


We are delighted to announce a third Call to Application. We are looking to fund further projects that will help find a cure and/or a treatment for any of the three types of myotubular myopathy (congenital X-linked recessive; congenital autosomal recessive; autosomal dominant), focusing on research that would not generally be funded by public or industrial funding sources. Our third Call will be open to research bodies internationally, for the first time.

To date, we have awarded research grants / fellowships for the following European projects:

  • Gene therapy for x-linked myotubular myopathy and pathophysiology – Dr Anna Buj Bello, Genethon, Evry.
  • Membrane trafficking and T tubule structure and function in a canine model of centronuclear myopathies – Dr Richard Piercy, Royal Veterinary College, London
  • Deciphering the molecular pathway involving centronuclear myopathy genes – Manuela D’Alessandro, IGBMC, Illkirch

In particular we would like to encourage the application of new technologies to research into myotubular myopathy, which may involve collaboration between different medical disciplines and / or different research institutions. We are also willing to consider applications which involve joint funding with other organisations.

Please see our Research Programme & Grants Information Page to read more and download an application form.


4.10.10 Faster Diagnostic Testing for UK Patients


The four genes so far identified as causing myotubular (MTM) and centronuclear myopathy (CNM), namely MTM1, DNM2, BIN1 and RYR1, can all now be tested for in the UK by Dr Stephen Abbs and his team in the DNA Laboratory of GSTS Pathology, Guy's & St Thomas' Hospital, London. For more information, and details about how you can be referred to this faster service, either as a UK NHS patient, or as an overseas private patient, please read more here.


8.9.10 A Third New Research Grant Is Awarded By Myotubular Trust


We are delighted to be able to announce the second year of Myotubular Trust research grants. Myotubular Trust put out a call for grants last September and after a rigorous application and peer review process our Scientific Advisory Board has recommended that we support an application from Dr Manuela D'Alessandro at The Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) in Strasborg, France. We have awarded Dr Manuela D’Alessandro a 3 year post doctoral fellowship of £120,000 for her exciting and innovative research project which is due to start in the autumn of 2010, and will help to find a cure or treatment for myotubular and centronuclear myopathy.

The characteristic feature of centronuclear and myotubular myopathy is the abnormal presence of the nucleus in the centre of the muscle cell instead of at the edge. What causes this centralisation of the nucleus or its relationship with the absence of myotubularin is not understood and it is this question which Dr D'Alessandro's research will address. She will be investigating how the different genes already implicated in centronuclear and myotubular myopathy interact with each other to instruct the muscle cell on where to position the nucleus. She will also investigate other genes known to be involved in the process of nuclear positioning and see how they act together too. If this 'molecular pathway' of genetic instructions, and exactly how this pathway causes centralisation of the muscle cell nucleus, could be better understood, it is likely to shed valuable light on the condition and possible future treatments. Dr D'Alessandro also hopes to identify new genes involved in positioning the nucleus and such genes may be appropriate as novel therapeutic targets to treat the symptoms of centronuclear and myotubular myopathy.

View the full lay report on this latest research grant.

Three Complementary Myotubular Trust Research Projects

By making this new grant to Dr D’Alessandro, the Myotubular Trust is now funding three complimentary areas of research and collectively, these grants use three of the available animal models to help in the research and investigation of the disease for better understanding. They address a number of the scientific questions most likely to lead to a therapeutic strategy to treat centronuclear and myotubular myopathy

The three areas of research we are funding now cover:

- Gene replacement therapy studies in the XMTM mouse with Dr Anna Buj Bello (INSERM, France);

- Detailed structural studies of muscle from Labrador dogs and human patients affected by these conditions, to learn more about the physical changes that occur in the muscles with Dr Richard PIercy (Royal Veterinary College, London);

- And this year’s grant to Dr D'Alessandro to understand more precisely the molecular pathway(s) in which 3 of the genes associated with MTM/CNM function.


8.9.10 Interesting Findings In Dr Piercy's Research Project

Dr Richard Piercy, whose work on the structural studies of myotubular and centronuclear myopathy muscles was funded by the Myotubular Trust last year, has recently presented some of his findings to the International Congress on Neuromuscular Diseases in Naples. You can read a short lay description from Dr Piercy of the progress his research is making here.


8.9.10 Model for X-Linked Myotubular Myopathy Found

Dr Anna Buj Bello, whose work we are supporting at INSERM in France, has, in collaboration with other leading international researchers, been involved in a major development in identifying a model for x-linked myotubular myopathy and has very positive implications for future research. You can read the full published article here.


18.9.09 A Second Call To Project


The Myotubular Trust put out a 2nd Call to Project on 18th September 2009. We will require completed applications by close of business Friday 18th December 2009.

We anticipate making awards in April 2010. We are looking to fund further projects that will help find a cure and / or a treatment for any of the three types of myotubular myopathy (congenital X-linked recessive; congenital autosomal recessive; autosomal dominant), focusing on research that would not generally be funded by public or industrial funding sources. This call will be open to European research bodies only. More....


10.9.09 Two New Research Projects Funded

The Myotubular Trust has now funded two research projects to address this important question from two different angles.

The first project, which will be run by Dr Richard Piercy, a Vet at The Royal Veterinary College, will try and understand what aspect of muscle function has stopped working properly in these muscle diseases. The second project, which will be run by Dr Anna Buj-Bello at INSERM, a French laboratory, will try a variety of therapeutic ‘rescue’ approaches such as gene therapy and drug administration.The research output from both of these projects is likely to suggest therapeutic strategies to treat MTM patients of all ages. More...

10.9.09 A Better Understanding About Research

Parents can often be intimidated by the medical jargon associated with a child's health condition but Dr Juliet A Ellis has kindly offered to help extend the work of the Myotubular Trust by providing affected families, carers and individuals themselves with simpler explanations about the European research taking place, helping us to achieve a better understanding of the possibilities of research and the language sometimes used by our doctors. More....

10.9.09 Our Grant Funding Process Explained


The Research Grant process which has led to the announcement of the first Myotubular Trust research grants is a complex process. There are four key stages to the process of making a research grant. For anyone wishing to know more about our process we have provided a fuller explanation here. More....