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
Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin
Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
24.05.2017 | Physics and Astronomy
24.05.2017 | Physics and Astronomy
24.05.2017 | Event News