Researchers from Children’s National Medical Center and colleagues in Tokyo publish results, video of first successful trial in dogs with Duchenne muscular dystrophy
Genetic researchers at Children’s National Medical Center and the National Center of Neurology and Psychiatry in Tokyo published the results of the first successful application of “multiple exon-skipping” to curb the devastating effects of Duchenne muscular dystrophy in an animal larger than a mouse. Multiple exon-skipping employs multiple DNA-like molecules as a “DNA band-aids” to skip over the parts of the mutated gene that block the effective creation of proteins.
The study, conducted in Japan and the United States, published this month in the peer-reviewed journal of the American Neurological Association, the Annals of Neurology, treated dogs with naturally occurring canine X-linked muscular dystrophy, a disease which is genetically homologous to the Duchenne muscular dystrophy that strikes 1 of every 3,500 boys born in the United States and worldwide each year.
Duchenne muscular dystrophy, one of the most common lethal genetic disorders, is an X-linked genetic mutation that causes an inability of the body’s cells to effectively create dystrophin—which builds muscle tissue. “Exon-skipping” employs synthetic DNA-like molecules called antisense as a DNA bandaid to skip over the parts of the gene that block the effective creation of dystrophin. Because the gene’s mutation could affect any of its 79 exons and sometimes more than one single exon at a time, scientists employed a “cocktail” of antisense called morpholinos to extend the range of this application. By skipping more than a single exon, this so-called DNA band-aid becomes applicable to between 80 and 90 percent of Duchenne muscular dystrophy patients, including the mutation found in dogs. “This trial makes the much-talked about promise of exon-skipping as a systemic treatment for Duchenne muscular dystrophy in humans a real possibility in the near term,” said Toshifumi Yokota, PhD, lead author of the study. “Of course this success has also introduced even more avenues for investigation, but these findings finally overcome a significant hurdle to our progress—we’ve solved the riddle of an effective system-wide delivery to muscle tissue, and seen promising results.”
A new state-of-the-art facility at the National Center of Neurology and Psychiatry in Japan was utilized to carry out the research.
“This study delivers the proof-of-concept that systemic anti-sense therapy can be done in a large organism, in Duchenne muscular dystrophy or any disease”, says Eric Hoffman, PhD, a senior author of the study and director of the Center for Genetic Medicine at Children’s National Medical Center.
“Systemic treatment of the majority of Duchenne dystrophy will require multiple sequences to be delivered in the blood, and this study also is the first proof-of-principle of multiple exon-skipping in any organism,” Shin’ichi Takeda, MD, another senior author, said. “In order to realize that promise in human trials, it also will be important to re-evaluate current measures of toxicity, efficacy, and marketing that ensure both safety for the patient, as well as rapid development and distribution of life-saving drugs.
The authors do note that significant steps still remain. Successful systemic treatment with morpholinos requires large doses of the antisense molecules—and the technology is costly and difficult to obtain. Additionally, treatment in this study showed diminished success at curbing muscle deterioration of the heart, meaning that a more effective and specific delivery system is needed to rescue the organ’s delicate tissue in Duchenne muscular dystrophy patients. However, these early successes do show much promise for the oft-discussed exon-skipping method as an effective treatment for Duchenne muscular dystrophy and some other genetic disorders. The post-treatment and non-treatment videos of the study are available on the Annals of Neurology website.
The study was funded by the Foundation to Eradicate Duchenne, the U.S. Department of Defense CDMRP Program, the Jain Foundation, the Crystal Ball Event of Hampton Roads and the Muscular Dystrophy Association USA, the National Center for Medical Rehabilitation Research, a collaborative grant from the U.S. National Institutes of Health Wellstone Muscular Dystrophy Research Centers, and several Grants-in-Aid from the Ministry of Health, Labour, and Welfare of Japan.Contacts
National Center of Neurology and Psychiatry of Tokyo: Atsushi Sakuma/Shin’ichi Takeda, +81-42-341-2711
Jennifer Leischer | EurekAlert!
Further reports about: > Cancer treatment > DNA > DNA band-aids > DNA-like molecules > Duchenne muscular dystrophy > Morpholinos > Neurology > X-linked genetic mutation > canine X-linked muscular dystrophy > dystrophy > genetic disorder > lethal genetic disorders > multiple exon-skipping > muscle tissue > muscular > muscular dystrophy
How cancer metastasis happens: Researchers reveal a key mechanism
19.01.2018 | Weill Cornell Medicine
Researchers identify new way to unmask melanoma cells to the immune system
17.01.2018 | Duke University Medical Center
On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.
We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
19.01.2018 | Materials Sciences
19.01.2018 | Health and Medicine
19.01.2018 | Physics and Astronomy