New Drug Approach Validated

This info is from 2018 but still very valid for today….. From Med Express

Researchers complete myotonic dystrophy treatment research

Translational Genomics group. Credit: Asociación RUVID

Researchers at the Translational Genomics laboratory of Valencia University and the INCLIVA health research institute have just discovered a new approach for the treatment of myotonic dystrophy, a rare and incurable neuromuscular disease which does not have specific treatment. Their work has been published in Nature Communications.

Their research has discovered molecules that are able to increase the expression of MBNL proteins, which are crucial for the , and that way prevent many of the alterations present in the murine and cellular models of the disease.

The uncovered molecules are known as antagomiRs. An antagomiR is a small oligonucleotide which has been noticeably modified to improve its pharmaceutical characteristics. It is added to specific regulatory RNA, in this case miR-23b and miR-218, which naturally suppress the expression of MBNL proteins. By degrading the suppressors, they increase endogenous expression, which is a therapeutic target for the disease. Oligonucleotides are a new type of innovative medicines which, according to Beatriz Llamusi, co-author of the project, “are quickly reaching clinical practice and could provide medium-term solutions for numerous diseases which are intractable today.”

Myotonic dystrophy originates due to expansions of the CTG triplet of the DMPK gene which, through a well documented process, abduct MBNL proteins and prevent them from carrying out their normal functions within the cell. Estefanía Cerro Herreros, first signer of the article, graphically describes this process: “It is as if we gathered all our teachers in a park instead of in a classroom: we would paralyse education.” She adds that “the treatment we have discovered consists of increasing the endogenous expression of said genes. As if, following the previous example, we hired more teachers.”

A crucial aspect of the research is the team’s interest on collaborating with the pharmaceutical industry to transform these discoveries into real medicine. Rubén Artero, head of the research, believes it is necessary to create an environment around research centres “which favours the continuity of scientific discoveries until they develop into solutions that are requested by society.” In this sense, the Translational Genomics group of Valencia University has previous experience with public-private collaborations focused on these developments and, in this specific case, is negotiating the creation of a spin-off company to progress in the development of these composites as potential therapies for . The research team recently organised the first Spanish convention on the use of oligonucleotides in human therapies (SMOT1) with broad participation of companies in the sector.

Print Friendly, PDF & Email

Exercise May help Strengthen Muscles in Myotonic Dystrophy

A new study ( But only of two people) shows that it is possible to increase muscle strength in Myotonic Dsytrophy. This study seemed to show that the exercise program needs to be adopted to the individual so that they maintain the exercise program. The Muscle strength increase seems to be linked to how diligent the person followed the training regime. From the Study:

Our results suggest that muscular adaptations linked to muscle growth can occur in DM1 as demonstrated by the CSA increase of type I and type II myofibers. Training might also influence the distribution of myofibers, in favour of type II. The myogenic and inflammatory markers evaluated do not seem to be modulated by the training stimulus in our participants. Compliance to the program seems to be an important factor to consider. Patient’s preferences regarding training regimen should be considered in the perspective of personalized training/precision medicine. It should be noted that beyond the positive impact of training on muscle adaptations, it could also bring positive changes in other organ systems. Further studies comprising a higher number of participants and controls are needed to validate our findings and determine to which extent and how skeletal muscles of DM1 patients adapt to strength training.


Print Friendly, PDF & Email

Cognitive Decline Over Time

A new study just published shows more information on cognitive decline over Time in DM1. This study shows different results than many other studies. Isolating the issues to just a few areas. It seems a very comprehensive study with multiple patients and controls which strengthens the results. Also a number of cognitive tests were included.


Print Friendly, PDF & Email

MDA awards $1 Million for Myotonic Dystrophy research

MDA Awards Nearly $1 Million to Continue Funding Myotonic Dystrophy Clinical Research Network

Investment will support five medical centers that specialize in DM research and clinical care

CHICAGO, January 24, 2017 – The Muscular Dystrophy Association announces the award of a clinical research network grant totaling $918,000 over three years to spur advances in myotonic dystrophy (DM) research.

Established in 2013, and supported by funding from MDA and other patient advocacy groups, the National Institutes of Health (NIH) and pharmaceutical company Biogen, the Network’s goals are to gain a more detailed understanding of the DM disease process and to collect data needed for clinical trials in order to inform what outcome measures, biomarkers and endpoints will be most appropriate.

“MDA is pleased to continue to enable this critical infrastructure for myotonic dystrophy research,” said MDA Scientific Program Officer Lianna Orlando, Ph.D. “Current and upcoming clinical trials in DM would not have been possible without MDA’s role in establishing the Network and supporting the creation of the tools necessary to carry out successful and informative studies.”

The Network currently is comprised of six medical centers with significant expertise in DM research and clinical care. Centers include:

  • California: Stanford University School of Medicine, Stanford
  • Florida: University of Florida College of Medicine, Gainesville
  • Kansas: University of Kansas Medical Center, Kansas City
  • New York: University of Rochester Medical Center, Rochester
  • Ohio: Ohio State University Medical Center, Columbus
  • Washington, D.C.: National Institutes of Health

MDA funds helped establish the Network’s original five university sites, and the new grant award continues to fund these programs. MDA funds do not support the NIH center. Additional sites may be added in 2017.

The Network is led by Charles Thornton, professor of neurology at the University of Rochester, who serves as its overall director.

“Now, for the first time, scientists and drug developers are coming up with good ideas about how to attack myotonic dystrophy at its root cause,” Thornton said. “The hope is that one of these new treatments will have a powerful effect, or that several can be used together.”

The Network was started, Thornton noted, to pave the way for testing new treatments in people.

“Experience has taught us that finding out whether a new drug is working or not is not a slam dunk. If we want to have clear answers, then we must work out many details and methods in advance,” Thornton continued. “And, we have to work closely with patients and families every step of the way. If it’s not a team effort, we probably won’t succeed.

“We are extremely grateful for support from MDA in getting the Network launched and keeping it going. When we started we hoped that we could encourage more companies and scientists to work on developing treatment for myotonic dystrophy, because they would see that all the tools are in place to conduct good clinical trials. Our work is still at an early stage but already we can see that this is happening.”

All of the researchers in the network have free and unrestricted access to data generated at all of the sites. In addition, and to further support advances in DM research, the Network is committed to making access to study results broadly available to both academic and industry researchers in the United States and around the world.

Among the Network’s accomplishments:

  • Network researchers have already been responsible for much critical clinical research in DM in the U.S., and through combined efforts they have standardized equipment and procedures (for measuring myotonic and muscle strength, and for obtaining blood and biopsy samples) across all sites.
  • The Network investigators published a DM biomarker study in December 2013 that looked at RNA splicing in muscle biopsy tissue and identified a group of gene splicing events that are affected even before there is evidence of muscle weakness. This collection of early changes in DM1 represent a tremendous opportunity for early/pre-symptomatic therapy intervention, and is being used as a potential biomarker to determine whether a treatment was effective at targeting the root cause of the disease process.
  • The five original Network centers are currently completing a multicenter observational study of type 1 DM in 100 individuals with the disease, while a companion study, conducted by the NIH site, is following 25 additional participants. The goals of both trials are to prospectively assess walking speed, muscle strength, muscle size, myotonia, heart rhythm, mental efficiency (attention, memory and cognitive tests), and overall health over a one-year period to determine how the condition changes over time.

MDA has funded more than $46 million in myotonic dystrophy research since 1950, and including this most recent award, is currently is funding nine active DM grants with a total funding commitment of more than $3 million.

The new grant was approved by MDA’s Board of Directors after careful deliberations and analysis by MDA advisors and research staff. This year, MDA is funding 150 different research projects in 11 countries.

About the Muscular Dystrophy Association
MDA is leading the fight to free individuals — and the families who love them — from the harm of muscular dystrophy, ALS and related muscle-debilitating diseases that take away physical strength, independence and life. We use our collective strength to help kids and adults live longer and grow stronger by finding research breakthroughs across diseases; caring for individuals from day one; and empowering families with services and support in hometowns across America. Learn how you can fund cures, find care and champion the cause at

Roxan Triolo Olivas
MDA Vice President Public Relations and Community Programs
(520) 529-5305

Print Friendly, PDF & Email

New DM1 Myotonic Dstrophy Drug in Development

Audentes Therapeutics Expanding Treatment Candidates for Duchenne MD and Myotonic Dystrophy Type 1

Audentes Therapeutics Expanding Treatment Candidates for Duchenne MD and Myotonic Dystrophy Type 1

Audentes Therapeutics is expanding its pipeline of potential molecular therapies, expecting to address 80% of patients with Duchenne muscular dystrophy (DMD) and all with myotonic dystrophy type 1 (DM1).

The treatment strategy, called vectorized exon skipping, uses a modified adeno-associated virus (AAV) to deliver antisense oligonucleotides (ASOs) — small molecules complementary to the RNA sequence — to skip over mutated exons, the bits of DNA that contain the information to generate proteins. Such an approach leads to the production of functional and full-length proteins.

According to Audentes, this strategy may be superior in DMD to microdystrophin gene replacement approaches, which produce shorter-than-normal dystrophin — the protein missing in these patients — with potentially less durable clinical benefits. Also, it may be more beneficial than current ASO therapies, whose efficacy is limited by poor distribution in muscle tissue.

“Today’s announcement represents a significant step forward in expanding our scientific platform and deepening our pipeline of product candidates for neuromuscular diseases with high unmet medical need,” Matthew R. Patterson, Audentes chairman and CEO, said in a press release.

Patterson also said Audentes believes that this strategy, combined with the company’s large-scale current good manufacturing practice (CGMP) manufacturing capability, “can deliver best-in-class therapies for the treatment of [DMD] and [DM1].”

The Muscular Atrophy News forums are a place to connect with other patients, share tips and talk about the latest research. Check them out today!

To accelerate these programs, Audentes reached a licensing agreement and will partner with the Nationwide Children’s Hospital, as well as two of its experts on neuromuscular diseases — Kevin M. Flanigan, MD and Nicolas S. Wein, PhD.

“We are excited to be collaborating with Audentes to advance these novel, highly differentiated approaches for DMD and DM1,” said Flanigan, director of Nationwide Children’s Center for Gene Therapy.

Audentes and Nationwide Children’s are collaborating to develop AT702, a treatment candidate designed for skipping of exon 2 of the DMD gene — which codes for dystrophin — in patients with exon 2 duplications and mutations in exons 1-5.

In mouse models, AT702 led to dose-dependent increases in production of full-length or near-full-length dystrophin and improvements in muscle function. The company expects to start a Phase 1/2 trial of AT702 at Nationwide Children’s in the fourth quarter of 2019.

Audentes is also conducting preclinical studies of two other vectorized exon-skipping candidates known as AT751 and AT753. These investigational treatments are intended for DMD patients with genotypes amenable for skipping of exons 51 and 53. Both AT751 and AT753 use the same viral vector backbone as AT702, enabling a potentially quicker clinical development, the company says.

Overall, these three potential therapies target over 25% of patients with DMD, with the company planning to leverage its exon-skipping platform to cover up to 80% of DMD patients.

Besides DMD, Audentes and Nationwide Children’s are assessing vectorized RNA suppression and vectorized exon skipping for DM1.  Both strategies have been validated in studies with ASOs and intend to prevent the buildup of toxic RNA of the DMPK protein in cells, a hallmark of DM1.

The company is currently conducting preclinical studies and expects to file an investigational new drug application in the U.S. for its selected DM1 treatment candidate, AT466, in 2020.

Audentes’ current manufacturing capability enables global commercialization of AT132, a potential therapy for X-linked myotubular myopathy and the company’s lead program, as well as continued clinical development of its pipeline programs. The facility is designed for an eightfold expansion of its production capacity.

Audentes recently hosted a conference call and a webcast on the expansion of its AAV technology as well as the DMD and DM1 programs. A replay of the webcast and slides can be found here.

José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
follow me
Print Friendly, PDF & Email