August 2024 Research Insights & Updates
The number of patients identified with RVCL has more than tripled in the last few years. The good news is that Dr. Jonathan Miner, Associate Professor of Medicine at the University of Pennsylvania, and our network of collaborators are making meaningful progress in finding a cure for RVCL. Today, we’re pleased to share an update on our website highlighting the Latest Research Insights.
We aim to continue providing regular research updates to our sponsors and supporters. Here are a few of our latest updates:
Breast Cancer Risk in Women with RVCL / RVCL-S
The latest video relates to our recent discovery that RVCL is associated with high-risk of early-onset breast cancer in women. We found that RVCL is a DNA Damage Syndrome, which means that the abnormal TREX1 protein causes injuries to chromosomes, leading to organ damage (mimicking radiation injury) and increased risk of cancer. Patients and families should be aware of this, as it may have implications for cancer screening. Please reach out to us if you have questions.
Collaboration Across Four Continents
The second video introduces you to our network of collaborators at the University of Michigan, around the United States, and also in Japan, France, Scotland, Australia, and beyond. These partners are helping us develop therapies. We also want to update that we have preliminarily confirmed that our gene therapy works in the livers of mice (after intravenous injection). We will have a long way to go, but our fruitful collaborations across four continents are creating a path toward personalized therapies:
WATCH BOTH VIDEOS HERE
Where Are We Today?
The task before us is challenging, and we cannot predict the timing. However, in just three short years, we have already achieved a great deal. We’ve managed to engineer mice to express the human TREX1 gene, and have determined a path to fix the mutation in adult mice, bringing us closer to a potential cure.
We are diligently working to develop small-molecule drugs. In collaboration with the University of Michigan, expert medicinal chemists are creating small-molecule drugs that bind the TREX1 protein and block its DNA-damaging effects. We have screened seven billion drugs and narrowed it down to a few hundred, with a lead compound already identified. We hope these drugs will eventually be taken as pills and that they will slow disease progression. The Clayco Foundation and others are accelerating this work by supporting us and engaging a contract research organization to synthesize new compounds for more rapid testing.
Our partnerships and shared goals—among patients, families, trainees, and staff in the lab, and our international collaborators—are making all of this possible.
Please get in touch with us if you need anything, and feel free to share these updates with your families and friends or anyone we might have inadvertently left off our list.
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 blindness, sickle cell disease, heart disease, nerve disease, cancer 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 disease, chronic 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.