MTM~CNM Family Conference

Dr. Martin "Casey" Childers- Wake Forest University

Dr. Casey Childers spoke to us from Wake Forest about some very promising potential treatments coming from his current work with Labrador Retrievers. Since MTM is a recessive trait for labs, the potential of looking at a variety of therapies using these large animal models is stagering. Dr. Childers manner of speaking was incredible, bringing home the potential that may come available to our community. Specific details cannot be put on this blog since these findings have not even been published, so we are really on the cutting edge! It was incredible to hear how he was shaping his study to meet the needs of our community, asking for input as to where our priorities lie in regards to potential treatments. Read more information regarding these exciting breakthroughs here: http://quest.mda.org/news/mda-awards-grant-test-mtm-gene-transfer-dogs.

Genathon, a French lab, is also making great strides in assisting our community. To read more about their approval with Boston's Children to begin gene therapy read here: http://www.genethon.fr/en/2011/07/21/genethon-and-childrens-hospital-boston-get-fda-approval-for-a-wiskott-aldrich-gene-therapy-trial/.

Following Dr. Childers was the tribute to our MTM Angels, one of the most emotional portions of the weekend. Honoring these sweet angels is a reminder to our entire community of who we are fighting for. Each family in attendance whose child became an angel the last few years received a beautiful plaque honoring their child. Each family was given an opportunity to speak.  It was an amazing experience. 

Soon the goodbyes began with the conference breaking for lunch. Reaserchers and attendees alike felt that this conference had touched a space in their hearts and drawn us together as a community. Remembering that as we begin to make our journeys home, we are a family that extends across the United States, across the pond, through Europe, Australia, and other parts of the world. We share a common bond. Our children and angels have provided us with a different view, a different path. We may not have expected to be here, but together we can do anything!

A slide show of all of our community was shown at the closing ceremonies and then final goodbyes.

The 2011 MTM-CNM Conference was amazing! For those of you who could not attend, you were missed, we thought of you often, and look forward to seeing you at the next conference.

Keep checking this site for updates in both the blog and cutting edge articles.

Until we see one another again....

Unfortunately, the blog that was typed during Dr. Dowling's talk was lost in the hotel's internet. Dr. Dowling's slide show will be posted soon and a blog interpretation posted at that time. Thanks for your patience.

Dr. Alan Beggs: MTM and the Centronuclear myopathies: Current researchers and prospects for therapies:

Objectives of talk: Define congenitla myopathy, Genetics of CNMs. "biology" of CNMs, animal models and approache to therapy.

Definition: primary hypotonia and weakness in early onset of like and relatively non-progressive. Distinctive and specific morphological abnormalities in skeletal muscle and main pathalogical feature. 

Blood tests search for the serum creatine kinase (CK) is usually normal or either mildly elevated, CMG's come out normal. Traditionally how the muscle looks under the microscope is how specific diagnosis come about. A specifi diagnosis may lead to specific genetic testing.

Dr. Beggs had a slide that was muscle tissue with four different stains to highlight different muscle diseases. Each slide highlighted the specific "look" of the disease.

In 1996 only two genes were known to be related to congential myopaties. Now (although he says the slide is out of date), there are more than 20 known genes that cause different congenital myopathies. There are commonalities at times between the genes and the different diseases

What about centronuclear myopathies? Normal adult muscle cells are nice, large, polygonal shaped cells with nuclei on the sides. WIth Centronuclear Myopathy the nuclei are in the center. Normal child muscle cells are smaller, but the nuclei are still on the side. Children with MTM have large nuclei in the center. Comparing these affected cells with those of a fetus approximately 23 weeks in gestation look very similar. Doctors call these early gestation muscle cell "myotubes," thus the diagnosis of Myotubular Myopathy.

Elizabeth DeChene, Genetic Counselor @ The Beggs Lab:

We inherit thousands of genes from our parents that we pass along to our children. Genes control pretty much everything we have. Genes are packaged into chromosomes which are made of combinations of 4 proteins (ACTG). These letters are in a variety of orders and each specific chromosome has a specific purpose. You can uses the analogy of a library. The library is the genome, you can go to a specific section (chromosome), get a specific book, and the order that the letters are in determine the word (gene).

MTM1 gene is myotubularin protein, which is X-Linked, It was discovered in 1996 and approximately 45% of patients have this mutation. DNM2, dynamin 2 protein which is dominant inheritance discovered in 2005 and approximately 15% of patients.

There is commercial genetic testing available. Sanger Sequencing is used to look at each gene. Currently only the exon is examined (the exon is what is being expressed.). Genetic testing can be used to find an accurate diagnosis, prognosis, carrier testing, family planning, prenatal diagnosis, and development of targeted treatment or cures.

Issues with genetic testing: multiple genes (need more than one test), expense, unidentified genes, RYR1 gene which is large (over 100 segments) and has many unique mutations.

Whole Genome Testing: Genome is 3 billion exons in length, so just the individual exons are examined. Now have 20 or 30 genes to look like. This technology is far more complicated and complex and may have a higher risk for error. Even with this, the specificity of the information in invaluable. It may not quite be ready to go "live" in clinical use. The isues are difficult to interpret, indication of enrelated findings and insurance may not cover. Benefits are that it is faster, less expensive, one-stop shopping, and follow-up analysis.

Contact Elizabeth at edechene@enders.tch.harvard.edu. Her phone number is 617-919-2169.

Dr. Alan Beggs: The biology

Gene mutated (MTM1) encodes myotuburin (Laporte, 1996) One part of the story that we are unsure of the importance is the abnormal desmin accumulation in MTM1 KO Mouse muscles.  It was found the myotubularin contrils desmin intermediate filament architecture and mitochondrial dynamics in humans and mouse skeletal muscle.

I will be attaching an article regarding a treatment for Myastheia Gravis that is now showing promise in treating children with MTM-CNM. >

Therapeutic approaches to CNM: Drug development, myobalst transfer (cell replacement therapy), myostatin inhibition. Myostatin is a protein that gets turns off in certain areas for growth. Without myostatin, there isn't an "off" switch for muscle growth. In mouse models, it has been shown that without myostatin are significant increase in muscle size and strength. Mice that have MTM that are treated with the myostatin inhibitor have more strength and live longer. This is a very exciting potential treatment for children with MTM. Unfortunately, there have been two rounds of testing on children with Duchenne's, but has been halted to due some mild side affects. Compaines and researchers involved are working to modify the compound and potentially return to trials.

There is now work being done on dogs with MTM-CNM gene. These dogs are the canine equivilent to children with MTM. There is exciting work being done with these dogs!

New Articles are posted under Documents & Articles. Dr. Beggs slide show will be posted later!.

We are breaking for lunch!

Wow! It's hard to believe that the conference is finally here! Last night we had family introductions, an incredible dinner, and time to bond.

Today begins the researcher talks! Dr. Dowling just gave an overview of the Natural History Study and why it is so important that you enroll your family. We would like to find a treatment or cure for MTM - CNM and the more information we can give the researchers, the further we can move forward!

Anne Rutowski, MD: Congential Muscle Disease Clinical Trial Readiness (CMDI)

Dr. Rutowsk is a licensed emergency room physician in the Los Angeles area. Her daughter, who is 13, has a congenital muscular dystrophy. She speaks of how she feels her story is similar to the journey many families with rare congential diseases. Her daughter was diagnosed when she was a baby with Cerebal Palsy. Shortly thereafter, their doctor gave them a diagnosis of congenital muscular dystrophy and found that it was a very rare form. She spoke with Dr. Mutoni in London and received an email stating her daughters diagnosis and was also informed that there was now a genetic test to determine the specific mutation. Her daughter was the first in the US to have the diagnosis of this specific fom of Congenital Myscular Dystrophy.

Dr. Rutowski and two other families formed the non-profit  http://www.curecmd.org with the goal of raising awareness and identify treatments. The vision is that one day all CMD children and adults have the opportunity to particiapte in a clinical trial. Congential Muscular Dystrophy and MTM-CNM have an overlap in medical condition and treatment.  For both to work together, we can share a , biobank, registry and tissue reposity which is more cost effective and ultimately work toward finding a cure. Doctors that are working on CMD are also working on Congential Myopathies (which MTM-CNM falls under.) 

Congential Muscle Disease Biobank: stores muscles, blood and tissue that (eventually) can be made available to doctors throughout the world, working to find a treatment and cure. For more information you can contact Tara Schmidlen, MS CGC, certified genetic counselor. COntact her at tschmidl@coriell.org. She can send you the information about blood draws and how to get enrolled in the study! It is a great opportunity!

CMD International Registry http://www.cmdir.org: is a patient and parent self repost on care and outcomes. Is has been translated into a variety of languages. Currently over 25 countries have participants which count over 400 at this time. It was initially focused on CMD but has been expanded through limb girdle spectrum (LGMD). This registry can act as a central hub for clinical study and trial information. It promotes diagnosis and genetic confirmation (where available) through national centers of excellence. It is also linked to the CMD Biobank and CMD GaP (Genotype and phenotype study).

Research: Looking for specific treatment/cure, animal models

Natural History Study:  To obtain approval, the FDA will not approve a drug to be used unless is can be a positive outcome on how a person with the disease feels and functions.

There is Strength in Numbers!

How you can help: donate to the CMD biobank if getting a blood draw, get involved in the Natural History Study, register with the CMD Registry, join the online Facebook group!