Florida Reseach finds new approach to treat Myotonic Dystrophy

Hope springs eternal when looking for treatments for this disease. There seems every month now that a new approach is in the works. This work by Dr. Disney and staff focuses on small molecules that will interface and destroy the RNA that are clogging the cells and causes these foci that seem instrumental in causing Myotonic Dystrophy. By targeting them and breaking them up this may give a treatment for the disease. Small molecules (Drugs) are pretty well known and understood by the medical community. So another approach. Lots of promise… but still we wait for more advances and clinical trials which are always in the future.



Scripps Florida Scientists Create New Approach to Destroy Disease-Associated RNAs in Cells

As Proof of Principle, Team Creates Molecule that Corrects Myotonic Dystrophy in Living Cells

JUPITER, FL, December 20, 2012 – Scientists from the Florida campus of The Scripps Research Institute (TSRI) have developed a new approach to alter the function of RNA in living cells by designing molecules that recognize and disable RNA targets. As a proof of principle, in the new study the team designed a molecule that disabled the RNA causing myotonic dystrophy.

The study, published online ahead of print on December 20, 2012 by the journal Angewandte Chemie, reports the creation of small molecules that recognize disease-associated RNAs, targeting them for destruction. Since small molecules are cell-permeable, the approach could have benefits over traditional methods of targeting RNAs for degradation, such as antisense or RNA interference (RNAi).

“We’re excited about these results,” said Matthew Disney, an associate professor at TSRI who pioneered the research. “This approach may allow for the inactivation of many cellular RNAs by small molecules and potentially lead the way to a whole range of novel therapeutics.”

It’s well known that gene expression can be controlled by triggering the degradation of messenger RNA—the blueprint for the production of proteins. This is accomplished through the recruitment of compounds that cleave or split the molecule. While several compounds can induce RNA cleavage in vitro, this has not been accomplished efficiently in living cells—until now.

In the new study, Disney and Research Associate Lirui Guan attached a rationally designed small molecule that targets the RNA that causes myotonic dystrophy type 1 with a molecule that produces hydroxyl radicals. Upon the small molecule’s recognition of the target, a hydroxyl radical was released that cleaved the disease-associated RNA, alleviating the disease-associated defects. Disney noted that, despite the compound’s producing a highly reactive species, the compounds are non-toxic at relatively effective doses.

The team accomplished this feat through what Disney calls a bottom-up approach to targeting RNA.

“We first identified the preferred RNA structural elements or motifs that bind to small molecules,” he said. “Then we looked at these elements in RNAs that cause disease and designed a binding molecule with increased affinity and specificity for those elements.”

Myotonic dystrophy type 1 involves a type of RNA defect known as a “triplet repeat,” a series of three nucleotides repeated more times than normal in an individual’s genetic code, resulting in a number of protein splicing abnormalities. Symptoms of this variable disease can include wasting of the muscles and other muscle problems, cataracts, heart defects and hormone changes.

The applications for this new approach could include cancer treatment in conjunction with other therapies, Disney said. The approach could also be used to create chemical probes of RNA function or to develop tools to probe RNA structure—provided, of course, that the RNA-binding preferences of the small molecules involved were well defined.

The study, “Small Molecule-Mediated Cleavage of RNA in Living Cells,” was supported by the National Institutes of Health (Grant number: R01-GM079235) and TSRI. For more information on the study, see http://onlinelibrary.wiley.com/doi/10.1002/anie.201206888/abstract.

Print Friendly

SRT-149 Myotonic Dystrophy & Autism Drug Candidate

Good news today! Another company has launched a potential drug for myotonic dystrophy and by extension this may also treat the childhood forms of myotonic dystrophy. The childhood forms of myotonic dystrophy are highly associated with autism spectrum disorder, so it is hopeful that this new drug will have some effects on this as well as the cognitive effects in the adult forms of the disease. For the general autism population reversing the effect in the childhood forms of myotonic dystrophy. May help narrow the mechanism of action and suggest certain treatments in the future. The childhood form of myotonic dystrophy is one of the few single gene causes of autism. Because the drug will work through an RNA mechanism, it is  unlikely this drug will have a direct effect on the general autism population.

Continue reading

Print Friendly

Arbaclofen – Will it help kids/adults with Myotonic Dystrophy?

While poking around looking for solutions and help in the autism area I found a lot of help and support. And I found a new drug that is being tested now in Phase II studies. Its being tested for a sister disease that has a lot in common with Myotonic Dystrophy. Fragile X is a triple repeat disease and has some symptoms similar to myotonic dystrophy kids.  Fragile X syndrome (FXS) is a genetic condition that causes intellectual disability, behavioral and learning challenges and various physical characteristics. Though FXS occurs in both genders, males are more frequently affected than females, and generally with greater severity.

Both of these diseases are single gene cause of mental retardation  and autism. Perhaps the drug that treats one may be applicable to the other.

The good news is that there is a drug in late stage development that might help with autism in kids with myotonic dystrophy. This drug is called arbacofen and has been successfully tested in not only in kids with fragile X but also in other kids with autism as well. The outcome is promising and the studies are continuing. Its fairly advanced with studies in the Phase IIb, which means they are getting close to commercialization.

Continue reading

Print Friendly

Donate Tissue and Body to Science Myotonic Dystrophy

Many people have asked if they can help with myotonic dystrophy research. I recently became aware of a program where at death you can donate your body to science and they will use tissue samples etc. to further research into myotonic dystrophy. The researchers are always in need of tissue samples and some of these can only be obtained after death.

Although the death of a loved one is devastating the gift of life in research can live on and others can benefit from the donation that is made. Think about this and see if it fits your needs and desires. IF desired fill out the pages and leave with your will.

The Paul and Sheila Wellstone Muscular Dystrophy center in Minneaplois, MN is coordinating this. The hot lines to call are (612)626-0822 and (612) 899-5964 Karac001@umn.edu

Please click here for the forms that are needed.

Print Friendly

What is a Possible Cause of Autism?

In doing a little digging about autism and myotonic dystrophy, Fragile X is a disease that pops right to the top of the screen. This is also a triplet expansion disease and it has a couple of similarities especially to some of the childhood forms of myotonic dystrophy. Fragile x causes mental retardation (Global developmental delay) as well as many of the kids have Autism or Autism spectrum disorder. Here is a review of Autism and Fragile X

Continue reading

Print Friendly