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Overview of MTM research
Recent breakthroughs (2005, 2006 and beyond)
Interviews with Dr. Gail Herman
Update from various
researchers around the world
Accessing the Medline Database
Overview of MTM / CNM research
There is considerable research being conducted on Myotubular Myopathy, both in the USA and in Europe. Much of the research is concentrated on the X-linked form of MTM -- because it is more common, the gene has been identified and it is easier to diagnose from family histories. Research is underway on the other forms of MTM, as well. The X-linked gene (called MTM1 for the myotubularin gene) was identified in 1990. Testing for MTM1 genetic mutations is available in the USA at the University of Chicago genetic laboratory. Genetic testing is crucial since the muscle biopsy alone can NOT reliably distinguish between the various genetic mutations that can cause myotubular/centronuclear myopathies. In November 2005, mutations of the dynamin 2 (DNM2) gene were identified as being responsible for an autosomal dominant form of centronuclear myopathy (CNM). As of the time of this writing (September 2006) genetic testing for the dynamin 2 gene mutations responsible for DNM2-CNM are not yet commercially available in clinical laboratories, so this testing is primarily provided within the research laboratory settings for the time being.
Much of the current MTM research in the USA is being performed at the Beggs laboratory at Children's Hospital Boston, part of Harvard University Medical School. The lab is under the direction of Alan Beggs, PhD, whose primary research area involves understanding the genetic and cellular aspects of congenital myopathies such as MTM/CNM, with a goal of finding treatments for affected individuals. The Beggs lab is currently actively enrolling patients and families affected by all forms of MTM/CNM. Research to help those affected by MTM/CNM cannot move forward without collaboration from affected families. Patients, families, physicians and researchers are encouraged to contact the Beggs laboratory as follows:
The Beggs Laboratory
Attention: Elizabeth Taylor
Division of Genetics, Enders 5
Children's Hospital
300 Longwood Avenue
Boston, MA 02115
Tel: 617-919-2169
Fax: 617-730-0253
Website: http://www.chb-genomics.org/hndp/research/beggs/
Email: etaylor@enders.tch.harvard.edu
Research is expensive and, unfortunately, for rare disorders such as MTM/CNM only a very limited amount of funds are available from government sources. Every penny counts as we work towards a cure. You can make a difference. Your generosity can help to ensure advances in cutting-edge research, improving the health of children with this rare disease everywhere. For more information on making a donation towards MTM/CNM research, please send an email to myopathy@optonline.net or call 973-882-1996. Donations are tax-deductible within the USA. "Matching funds" may also be available through your employer (just ask your human resources department at work). Also contact us if you are interested in hosting a fundraiser (such as walkathons, marathons, etc.). Just contact us and we can brainstorm ideas together. Funds raised are used to directly sponsor MTM/CNM research by Dr. Alan Beggs at Children's Hospital Boston, affiliated with Harvard Medical School. We would love to hear from you.
If you prefer to write a check, make it payable to "Children’s Hospital Boston" and write “Foye Fund” in the memo and mail it to “Foye MTM/CNM Research Fund, Children's Hospital Boston, care of: 38 Buckingham Circle, Pine Brook, New Jersey, 07058-9506, USA. If you have any questions, please call 973-882-1996 or e-mail myopathy@optonline.net. Thank you!
Generous funding for research on MTM/CNM and other similar congenital myopathies is provided by the Joshua Frase Foundation. More information about the Foundation and their programs is available at their website or by contacting them at 1-888-817-JOSH (That’s 1-888-817-5674). The Joshua Frase Foundation is a major network for families, doctors, and researchers interested in MTM/CNM. The JFF provides educational opportunities as well. For example, in autumn 2006 Sarah Foye in New Jersey, USA, organized the first ever international teleconference series on MTM/CNM, sponsored by the JFF.
Some funding for MTM/CNM research is also provided by the Muscular Dystrophy Association (MDA).
Myotubular Myopathy research in France is supported in part through the Association Francaise Contre les Myopathies.
In general, research in Europe is coordinated through a myotubular myopathy consortium under the sponsorship of the European Neuromuscular Centre (ENMC).
Research continues on other fronts in addition to locating the X-linked gene. Topics under investigation include:
Recent Breakthroughs (2005-2006)
(This web page was last updated: November 26, 2006.)
Revisions to this section ("Recent Breakthroughs") are currently underway. Substantial advances have been made in the understanding of MTM/CNM since the time of the last update of this section, so substantial revisions are necessary and will eventually be forthcoming. Meanwhile, suffice to say that 2005 was a landmark year with the identification of the dynamin 2 (DNM2) gene mutations as being responsible for the autosomal dominant form of centronuclear myopathy. In 40 years since myotubular/centronuclear myopathy was first described (1966), this 2005 discovery marks the second gene identified as being responsible for a form of MTM/CNM. DNM2-CNM typically presents with onset of weakness during adolescence or early adult years. The previously identified form is the X-linked (usually congenital onset, i.e. apparent at birth) form caused by mutations of the MTM1 myotubularin gene. The November 2005 medical publication (journal article) announcing the identification of DNM2-CNM was a collaborative effort between researchers at the Beggs laboratory at Children's Hospital Boston and researchers in France. Such collaboration is particularly important for conditions such as MTM/CNM, since the rarity of the disorders often results in only a very limited number of involved patients at any given hospital or research laboratory. We applaud researchers such as these who work together with colleagues worldwide to help make advances that will benefit affected children and families.
Another significant advance has been clarification of the terminology regarding "myotubular" myopathy versus "centronuclear" myopathy. The physicians and researchers traditionally have used these terms relatively interchangeably. However, a 2005 review article by Dr. Pearson and Dr. Beggs (and colleagues) clarified that all myopathies with a muscle biopsy showing the nucleus located in the center (rather than located in the normal location at the periphery of the muscle cells) can be referred to as "centronuclear" (nucleus in the center) myopathy. Thus, centronuclear myopathy (CNM) is the "umbrella" term that includes subcategories such as "myotubular myopathy" (also referred to as X-linked MTM or MTM1), dynamin-2 centronuclear myopathy (DNM2-CNM), as well as other forms of CNM for which the involved gene has not yet been identified (e.g., autosomal recessive forms). Thus, CNM is the inclusive term for all of these myopathies, with "myotubular myopathy" (X-linked MTM) apparently being the most common form of CNM.
A published medical journal article in September 2006 documented the oldest known person living with myotubular myopathy (MTM). This was a 68-year-old male whose genetic testing was positive for the same MTM1 gene mutation as was diagnosed in his grandson. The grandson had onset of symptoms congenitally and was diagnosed at that time, prompting the testing in the grandfather, which showed the same genetic mutation at MTM1, despite differences in the severity of their symptoms. Obviously, multiple factors are involved in the manifestations of MTM. This is an area of active research interest. This article also highlights the importance of genetic testing whether the individual is severely involved or only mildly symptomatic.
* * * *
Further revisions will be forthcoming to this "Recent
Breakthroughs" section. Older
sections (1990’s) of this web page are below.
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An article in the February 1999 edition of the Journal of Pediatrics describes medical complications and gives updated information on outcomes for kids with X-linked MTM. Among the findings from studying 55 males from 49 different families is that
This article has several profound implications. First of all, it substantiates what we've been saying for years: With the appropriate interventions, kids born with Myotubular Myopathy often survive. Second of all, by linking several other disorders to the XMTM gene, it increases survivability of these kids by giving physicians a "heads up" on other potentially serious problems to be aware of. Third, by examining the linkages of these other disorders, we hope that furutre researchers are able to get some insight into the exact role that the XMTM gene plays in muscle development.
We have attached a copy of the abstract of this article to this website.
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There have been several recent breakthroughs in locating the gene responsible for the X-linked version of myotubular myopathy. The Medline database is the best source for learning about some of these breakthroughs.
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An article in the MDA magazine Quest (also mentioned elsewhere on this website) contains the story of MTM research in the US as well as an update by a researcher at Case Western Reserve.
Interviews with Dr. Gail Herman
More information about on-going reserach can be found in two different interviews with Dr. Gail Herman of Ohio State University. Dr. Herman is one of the world's leading experts on Myotubular Myopathy and is a good friend of this resource group. These interviews, which originally appeared in our newsletters, provide good insight into her work, some of her findings and her view of MTM research in general.
Update from various researchers around the world
Under the sponsorship of ENMC, MTM researchers from around the world regularly convene and jointly plan their work. Below is a summary of the last conference, held in March 1998: (Note, this summary was copied from the ENMC web site. We copied it rather than linked to it in order to make it a little easier to get to.)
Myotubular Myopathy
20th to 22nd March 1998, Naarden, The Netherlands
The ENMC held its 58th Workshop in Naarden, The Netherlands on Myotubular Myopathy, an uncommon congenital myopathy that often results in the death of affected infants. Fourteen participants from eight countries presented the recent results of their studies, and together planned a programme of future work. The current methods of choice for molecular diagnosis were discussed; the initial antibody studies of the myotubularin protein appear promising. The preliminary results from a collaborative clinical and molecular genetic database were generated. This work suggests a correlation between the nature of the mutation in the X-chromosome MTM1 gene and the severity of the disease in affected males.
Future work will address the function of the myotubularin protein, the progression of the disease process in affected individuals and the autosomal (non-sex-linked) forms of the disease.
Carina Wallgren-Pettersson (Helsinki, Finland) and Angus Clarke (Cardiff, United Kingdom) Organisers of the Workshop
Accessing the Medline Database
The Medline database is available from the National Center of Biological
Information, a project sponsored by the National Institutes of Health and the
National Library of Medicine. It contains abstracts and information about
many, many genetic diseases. This is a free web site open to the public.
To access this resource go to the PubMed site at http://ncbi.nlm.nih.gov/PubMed
. Once your there, search for Myotubular Myopathy.
Alternatively, click
on this sentence for an even quicker link to those medical abstracts on
Myotubular Myopathy (MTM).
Similarly, click
on the sentence for a quick link to medical abstracts on Centronuclear Myopathy
(CNM).