Rare Disease’s DNA-Damaging Mutation Could Have Consequences for More Common Conditions

Jonathan Miner, MD, PhD, and his research team at the University of Pennsylvania Perelman School of Medicine and the Brain Research Institute at Niigata University have furthered their understanding of RVCL.

While it was already known that a mutation in TREX1 was behind RVCL, the mechanism by which it did its damage was not known. A new study published in Nature Portfolio highlights that TREX1 speeds up the typical process of DNA damage—a process some theorize is tied to every animal’s aging process—the researchers may not have only discovered the weapon TREX1 uses on RVCL patients but also offered insight beyond this hashtag#raredisease population.

Studying RVCL models in animal and human cells, Miner and his colleagues explored their hypothesis that the TREX1 mutation, which shortens the gene, was causing instability within cells and damage that appears similar to breakdowns seen in radiation injuries.

They found that the mutation was interfering with a DNA repair process, which occurs when there is a break in both strands of DNA. This interruption of the process allowed DNA to be deleted, and cells prematurely aged and stopped dividing, which leads to overall premature aging and organ damage.

The study’s findings provide a clearer picture for the types of treatments and medicines that could be pursued for people with RVCL. They could involve lowering levels of TREX1 in the body, correcting the mutation, or just blocking the gene’s DNA-damaging effects.

This is a hopeful development for those living with RVCL and offers a glimpse into the future of aging research. You can read the complete update here.

The New York Times: We Can Cure Disease by Editing a Person’s DNA. Why Aren’t We?

Earlier this year, the RVCL.org team published an update that provided a brief overview on how the discovery and use of CRISPR-Cas technology can be helpful in treating different diseases. Furthermore, the post hypothesized how CRISPR-Cas could be utilized to repair the mutant TREX1 and restore RVCL patients to a healthy stature.

The first person to be gene-edited with CRISPR was treated only three years ago for a disorder of red blood cell production, and since then, the technology has been used to treat congenital blindnesssickle cell diseaseheart diseasenerve diseasecancer and H.I.V. While not all diseases have a single-gene basis, most have a genetic component. Early studies suggest that conditions like heart diseasechronic pain and Alzheimer’s disease could all be treated with CRISPR. ‌Dr. Jennifer Doudna, a winner of the 2020 Nobel Prize in Chemistry for CRISPR gene editing along with Dr. Emmanuelle Charpentier, aptly described it as a “profound opportunity to change health care for many people.”

Guest author from the New York Times, and professor of molecular and cell biology at the University of California, Berkeley, Fyodor Urnov, published an important article last week that highlights the history, ongoing trials, future regulation, and funding that needs to occur to ensure that CRISPR technology is available for all.

The use of CRISPR technology continues to be utilized around the globe, and its invention has provided us with the opportunity to provide remarkable treatment for rare diseases. It is stories like these that continue to shed a light on rare diseases and further illustrate the possibilities of what CRISPR can accomplish.

You can read the entire article by following the provided link (soft paywall).

The Clayco Foundation Teams Up with Experienced Researchers from the Netherlands

The Clayco Foundation RVCL Venture is teaming up with a highly qualified and RVCL-experienced group of researchers in the Netherlands to increase the scope of research and of patient identification and aid.  This kind of global connection is one of the exact reasons this venture was created and an example of where effort is being focused. With this trans-Atlantic relationship, research will be able to be expedited and we just may get to treatment options sooner.