Spring 2022 Distinguished Public Lecture – Dr. Eric Olson and CRISPR-Cas9 Gene Editing – The Paisano

On Monday, April 25, UTSA’s Neurosciences Institute & Brain Health Consortium presented the Spring 2022 Distinguished Public Lecture. Eric Olson, Ph.D., Professor and President of UT Southwestern Medical Center led the presentation on CRISPR technology -Cas9 and the advances it has made in neuromuscular and cardiac diseases.

Dr. Olson began his presentation by demonstrating the importance of muscle in living organisms. He claimed that muscle gives meaning to life and there is no life without muscle. Following this, he presented the many genetic mutations that cause muscle dysfunction and disease.

“There are hundreds of muscle tissue diseases in humans caused by mutations in genes with a wide variety of functions, and there is no single cure for any of them. The most devastating of all muscle diseases is Duchenne muscular dystrophy,” said Dr. Olson. “This disease has been known for more than 150 years since it was first identified around the 1870s by a French neurologist. [named] Duchenne.

Dr. Olson also noted that Duchenne is essentially a chronic, incurable condition found in boys that almost always results in premature death.

No patient with Duchenne has ever escaped this series of clinical events. The muscle degeneration in these boys leads to their confinement from the wheelchair to…then they lose the use of their arms and they need ventilation because the diaphragm is a muscle necessary for breathing, ultimately, and it leads to [to] heart failure and death from [their] mid-20s,” Dr. Olson said.

Riley Carroll

But thanks to the breakthrough in CRISPR-Cas9 gene editing, test subjects with muscular dystrophy who were genetically modified showed significant success. CRISPR-Cas9 allows medical professionals to modify the DNA of a living organism. This technology has already been used by He Jiankui, a Chinese geneticist, who genetically modified a set of twins who had an inherited predisposition to HIV. Jiankui’s successful experiment with twins sparked huge controversy in 2018, but now Dr. Olson is testing this miraculous innovation on young boys with a rare muscle disease.

After the remarkable results of CRISPR in previous subjects, Dr. Olson and his team experimented with dogs that had Duchenne.

We wanted to ask ‘Can we really do this in a large animal beyond a mouse?’ Many diseases had been cured in mice and… so we searched around the world and found that [at] the Royal Veterinary College in London, [was] a family of dogs that had the deletion of exon 50 in dystrophin, the most common exon deleted in boys with Duchenne, and the exon we have already corrected in human cells in myosin. This original dog belonged to an elderly lady in London – it was her favorite dog and the dog struggled up and down stairs,” Dr Oslon said. He then shared a short video clip showing the running puppies before and after the gene edit. Before, the dogs were clearly hampered in their abilities, almost hopping rather than running, but afterwards they seemed to run almost exactly as a normal animal would.

The only downside to the treatment is the expense it requires to perform.

“The general idea is that gene therapies are one-time therapies for the rest of a person’s life – it would probably be in the $1 million range. And that price… will come down. But the basis for pricing these gene therapies is entirely based on the manufacturing costs to produce the virus. So as people find better viruses…those costs will come down significantly,” Dr. Olson said.

For informational videos about Dr. Olson and his work, visit the following YouTube links.

https://www.youtube.com/watch?v=11l5jANLjAQ, https://www.youtube.com/watch?v=bMLuERSGd8g, https://www.youtube.com/watch?v=eCvYT-XvD3M, https://www.youtube.com/watch?v=5oulMwwtyaM.

Angela C. Hale