Recruiting for the Myotonic Dystrophy Drug study is beginning. You must contact the individual centers to insure that you may have a chance to be included in the study. The study has only a very limited number of individuals that can be included. If you have joined one of the registries for myotonic dystrophy….this is not sufficient or enough. Call or email the centers as soon as you can and ask to be included in the drug trial if you meet the criteria.
This week ISIS pharmaceuticals announced the commencement of recruiting for Phase I of the Myotonic Dystrophy Drug Trial. This is tremendous news for the myotonic dystrophy community. The promise of scientific research to define the DNA site, identify the cause of the disease, then begin to develop treatments that would reverse the problems in the cell are culminating to the promise of hope for all that suffer from this horrible affliction.
If you want to participate in this study you must act quickly and contact the centers that are conducting the research. Find the closest location and contact the person via email or phone. You must meet all (meaning all) the qualifications for the trial. The full information is on CLINICALTRIALS
Most of the emphasis on myotonic dystrophy has been on DM1 or Myotonic Dystrophy Type 1 Now a new generous gift will push the reseach front on DM2! A great day!
Gift Will Advance Research on Myotonic Dystrophy Type 2
September 09, 2014
A $1.25 million gift from Lilyan (Lil) and Albert (Alfy) Nathan of Florida and Michael and Sherry Goldberg of Chicago will create a new center dedicated to research on myotonic dystrophy type 2 (DM2) at the University of Rochester School of Medicine and Dentistry. The gift will be used to support a new research program that will be led by UR Medicine neurologist Chad Heatwole, M.D.
Scientists uncover most detailed picture yet of muscular dystrophy defect then design targeted new drug candidates
Scientists from The Scripps Research Institute have revealed an atomic-level view of a genetic defect that causes a form of muscular dystrophy, myotonic dystrophy type 2, and have used this information to design drug candidates with potential to counter those defects — and reverse the disease.
“This the first time the structure of the RNA defect that causes this disease has been determined,” said TSRI Associate Professor Matthew Disney, who led the study. “Based on these results, we designed compounds that, even in small amounts, significantly improve disease-associated defects in treated cells.”
Myotonic dystrophy type 2 is a relatively rare form of muscular dystrophy that is somewhat milder than myotonic dystrophy type 1, the most common adult-onset form of the disease.
Both types of myotonic dystrophy are inherited disorders that involve progressive muscle wasting and weakness, and both are caused by a type of genetic defect known as a “RNA repeat expansion,” a series of nucleotides repeated more times than normal in an individual’s genetic code. The repeat binds to the protein MBNL1, rendering it inactive and resulting in RNA splicing abnormalities — which lead to the disease.
Many other researchers had tried to find the atomic-level structure of the myotonic dystrophy 2 repeat, but had run into technical difficulties. In a technique called X-ray crystallography, which is used to find detailed structural information, scientists manipulate a molecule so that a crystal forms. This crystal is then placed in a beam of X-rays, which diffract when they strike the atoms in the crystal. Based on the pattern of diffraction, scientists can then reconstruct the shape of the original molecule.
Prior to the new research, which was published in an advance, online issue of the journal ACS Chemical Biology, scientists had not been able to crystallize the problematic RNA. The Scripps Florida team spent several years on the problem and succeeded in engineering the RNA to have crystal contacts in different positions. This allowed the RNA to be crystallized — and its structure to be revealed.
Using information about the RNA’s structure and movement, the scientists were able to design molecules to improve RNA function.
The new findings were confirmed using sophisticated computational models that show precisely how the small molecules interact with and alter the RNA structure over time. Those predictive models matched what the scientists found in the study — that these new compounds bind to the repeat structure in a predictable and easily reproducible way, attacking the cause of the disease.
“We used a bottom-up approach, by first understanding how the small components of the RNA structure interact with small molecules,” said Jessica Childs-Disney of TSRI, who was first author of the paper with Ilyas Yildirim of Northwestern University. “The fact that our compounds improve the defects shows that our unconventional approach works.”
- Jessica L. Childs-Disney, Ilyas Yildirim, HaJeung Park, Jeremy R. Lohman, Lirui Guan, Tuan Tran, Partha Sarkar, George C. Schatz, Matthew D. Disney. Structure of the Myotonic Dystrophy Type 2 RNA and Designed Small Molecules That Reduce Toxicity. ACS Chemical Biology, 2013; 131216144058009 DOI: 10.1021/cb4007387