Autoimmune diseases occur when the immune system malfunctions and mistakenly attacks and damages healthy cells. HSS is a leader in research on these conditions, which include lupus and rheumatoid arthritis, and currently our scientists are studying disease pathways that could become therapeutic targets for these difficult-to-treat conditions. We asked Alessandra Pernis, MD, Senior Scientist and The Peter Jay Sharp Chair in Lupus Research, for an update on cutting-edge research involving an important molecule called ROCK, which has been found to be overactive in some patients with autoimmune diseases.
Q. What is ROCK?
Dr. Pernis: ROCK is a Rho kinase, which is an important molecule that controls immune function. It has been found to be overactive in some patients with autoimmune diseases, such as lupus and rheumatoid arthritis. There are two types: ROCK1 and ROCK2. Studies show that blocking certain ROCKs can calm the immune system. The molecule also plays a role in injury repair, so we are collaborating with HSS orthopedists and the Precision Medicine Laboratory to investigate healing after total knee replacement.
Q. What is the goal of the research?
Dr. Pernis: We are hoping to discover new therapies for autoimmune diseases. There has been only one new lupus drug introduced over the last 15 years, and there are subsets of rheumatoid arthritis patients that have failed existing treatments. Scleroderma is another disease that is in dire need of new treatments. The studies in our lab are focused in large part on the ROCK pathway. A number of ROCK inhibitors have been, and are being developed, and we want to determine which type of inhibitor might work best for each individual patient. It’s a personalized medicine approach.
Q. Why is this research groundbreaking?
Dr. Pernis: We’ve discovered a fundamental pathway in the development of autoimmune diseases, and it may lead to new and better treatments.
Q. What is the status of your research?
Dr. Pernis: Our latest study shows that ROCK activity levels are significantly higher in lupus and rheumatoid arthritis patients compared to healthy individuals. Our research also indicates that several different ROCK inhibitors may be effective in reducing the molecule’s activity level. In particular, we are looking for signals within specific sets of genes that could help identify whether a patient would respond better to blocking ROCK1 or ROCK2.
Q. How soon could patients benefit from this research?
Dr. Pernis: In five years, we expect to have a blood or tissue test that will allow us to determine which ROCK inhibitor will work best for each individual patient.
Q. What are you most proud of to date?
Dr. Pernis: Every time we test a new hypothesis, it reinforces the notion that the ROCK pathway plays a key role in autoimmunity. This tells you we’re going down the right path. It’s always exciting when you’re finding new opportunities for treatment.
Q. What is unique about research at HSS?
Dr. Pernis: Research is fundamental to orthopedic surgery, and we share our knowledge with our orthopedist counterparts. We can determine if the treatment pathways that work for autoimmune patients also work for surgical patients. It’s this culture of learning that really sets our research efforts apart from those of other institutions.
Dr. Alessandra Pernis is a Senior Scientist and The Peter Jay Sharp Chair in Lupus Research at Hospital for Special Surgery.