With a deft snip, potential treatment emerges for deadly childhood Duchenne Muscular Dystrophy

Wow! A treatment for Duchenne’s muscular dystrophy, the most malignant and life shortening kind of dystrophy. This will be miraculous for the individuals who have Duchenne’s and their families.  And the CRISPR/Cas9 gene editing technology, which allows more precise editing of genes, is an amazing technique. It comes from bacteria and it is the bacterial immune system, CRISPR is how bacteria disable bacteriophages (viruses that infect bacteria and kill them) and plasmids. The bacteria ingeniously insert the phage and plasmid DNA in between certain sequences in their chromosome, then in a process mediated by RNA, use a nuclease to cleave and inactivate the phage and viral DNA! Ingenious indeed! This is the very process that is now starting to be used to perform gene therapy for diseases in animals and humans.


Using cells from patients with Duchenne Muscular Dystrophy, a genetic disease that affects one in 5,000 boys, UCLA scientists have devised a strategy for creating “corrected” stem cells that could restore tissue under attack by the deadly muscle-wasting disorder.

A gene-editing procedure described by researchers Thursday in the journal Cell Stem Cell resulted in a gene that functions properly, coding for the production of proteins called dystrophins, which are deficient in people with Duchenne Muscular Dystrophy (DMD). It could lead to one of the first therapeutic uses of a controversial new gene-editing technique known as CRISPR/Cas9.

This feat of genetic surgery is a key step in the development of a therapy that could treat DMD.

The leading childhood form of muscular dystrophy, DMD progressively destroys the musculature of affected boys and typically leads to death in their mid-20s. In patients with DMD, a genetic defect disrupts the production of dystrophins, which are essential for the growth, protection and normal function of heart and skeletal muscle.

Working together, scientists from UCLA’s Broad Center for Regenerative Medicine and Stem Cell Research and its Center for Duchenne Muscular Dystrophy focused on the largest known human gene, where the DNA sequences implicated in DMD are nestled in among many others.

Taking a skin cell from a Duchenne patient, they first reprogrammed that “fibroblast” to revert to a primitive stem-cell form.  They located a long stretch of that gene that appeared to produce the dystrophin defect, and used “guide DNA” — tiny homing mechanisms — to snip away the offending sequence at either end. Finally, they spliced the altered gene back together.

By this method, the team had engineered a stem cell capable of giving rise to skeletal muscle or heart tissue with dystrophin production that is nearly normal. If it could be reintroduced into the Duchenne patient from which the original stem cell came, it should be a perfect fit — and potentially powerful therapy.

“We knew it was a large region of the gene to delete,” said study co-author Courtney Young, a graduate student at UCLA’s molecular biology institute. “To cut in two places at the same time and get them to join together: we weren’t even sure it would work.”

The editing trick was akin to making a dining room table with elaborately turned legs into a functional coffee table: Young had to find a way to cut out a piece of each leg and splice the remaining ends together so they lined up perfectly. When the team tested the edited stem cell, they could see that it would function normally.

For Young, it was more than a scientific victory. She has a 9-year-old cousin with DMD. That she could help him or others with the disease, she said, “makes it more meaningful.”

The next step, said study co-author April Pyle, a stem cell biologist and lab director at the Broad Center, will be to “cut out the middleman” and perform the editing technique on stem cells derived directly from patients’ muscles.

That is just one of many steps that must be taken before this gene-editing procedure could be used to help patients with DMD. As in other potential uses of CRISPR/Cas9 gene-editing, researchers will have to ensure they have not inadvertently added or snipped out genetic sequences with unanticipated “off-target” effects. And they still must find efficient ways to introduce cells with the edited DNA into patients so that those “corrected” cells can establish themselves and restore muscle function.

If all those steps come together, said co-author Melissa Spencer, “this kind of therapy would be a permanent correction.” Because these cells effectively clone themselves, “you don’t  need to fix every stem cell” to overcome the debilitating effects of a genetic disorder.

“You could have, not a cure, but a very, very effective therapy for a large number of patients.”

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