from the meatheads dept.
Brain involvement in Duchenne muscular dystrophy was described by Duchenne de Boulogne himself in 1886. It has been largely ignored.
Duchenne muscular dystrophy (DMD) is a fatal genetic disorder that predominantly affects male children. There is no cure. Besides severe muscle wasting, the disease also affects the brain.
DMD is caused by DNA mutations that result in the body-wide loss of a protein called dystrophin. Dystrophin is essential for muscle strength and function. It acts like a shock absorber, without it muscles become weak and break down. Most affected children will be in wheelchairs by their early teens with death typically occurring in early adulthood because of complications with the heart or lungs.
Duchenne is first and foremost a muscle disorder, but the intelligence of individuals with the disease is lower than the general population. Intellectual disability, epilepsy, autism and attention deficit hyperactivity disorder are also common. Mounting evidence links these symptoms to the loss of dystrophin in the brain. But given the more urgent need to treat the muscles, brain involvement in DMD has been ignored.
So what does dystrophin do in the brain and why is its loss linked to cognitive and behavioural problems? We understand very little. Unlike muscle, the brain produces several different types, or isoforms, of dystrophin. These are found in different regions of the brain, and in different parts of the cell. Proposed functions are therefore diverse and range from a scaffolding function in the nucleus to roles in synapse activity.
[...] The lack of understanding of how dystrophin functions in the brain is a major roadblock to the development of effective whole-body treatments. There is an urgent need for fundamental research in this area. My postgraduate research student, Amanda Ash, and I have this month launched a crowdfunding campaign to raise awareness and funds to help kick start such work. The platform, Experiment, recently surpassed £1,000,000 in total funding raised. Scientists using the platform have been featured in The Economist, Forbes, Nature, and The New York Times.
A new and non-viral approach to CRISPR has been used to treat Duchenne muscular dystrophy in mice:
A new version of the CRISPR-Cas9 gene-editing technology called CRISPR-Gold has successfully restored the correct sequence of the dystrophin gene in a mouse model of Duchenne muscular dystrophy (DMD), a new study revealed.
Researchers found that an injection of CRISPR-Gold into DMD mice led to an 18-times-higher correction rate and a two-fold increase in a strength and agility test compared to control groups, according to a press release.
The study, "Nanoparticle delivery of Cas9 ribonucleoprotein and donor DNA in vivo induces homology-directed DNA repair," [DOI: 10.1038/s41551-017-0137-2] [DX] was published in the journal Nature Biomedical Engineering.
[...] Unfortunately, methods of delivering the components of this system, which include an RNA molecule called a guide RNA, a protein called the Cas9 nuclease, and the correct DNA sequence to replace the mutation (via donor DNA), have not been fully developed for human use. A primary technique used to deliver the components of this system relies on viruses, but this technique is plagued by complications and unwanted side effects.
In response, researchers at the University of California, Berkeley have developed a new approach called CRISPR-Gold, which used gold nanoparticles to deliver the components of this system in a mouse model of DMD. This method works by using gold nanoparticles to coat a modified DNA molecule that binds the donor DNA, which in turn is bound to Cas9 and the guide RNA.
This entire system is then coated by a polymer that will interact with a cell membrane and allow entry into a cell. Then, the components of the system are released into the cell as the coat breaks apart upon entry. The guide RNA, the Cas9 nuclease, and the donor DNA can then make their way into the nucleus and correct the mutation.
Also at TheScientist.
Previously: FDA Panel Recommends Rejection of Duchenne Muscular Dystrophy Treatment
Marathon Pharmaceuticals is Part of the Problem
Marathon Pharmaceuticals Cashes Out on Regulatory Loopholes
What is a Muscle Protein Doing in the Brain?