Learn from Livie
Multisystemic Smooth Muscle Dysfunction Syndrome (MSMDS) is a disease that affects all the organs in the body that depend on smooth muscle cells for proper function. MSMDS is rare, but has a very high risk of early death when present. The disease is caused by changes in a gene that is critical specifically in vascular smooth muscle cells (a special type of smooth muscle cell that lines blood vessels). This gene, ACTA2, causes MSMDS when the genetic code for one of the amino acids in the ACTA2 protein, arginine at position 179 (p.Arg179) causes a change to another amino acid.
MSMDS can cause fixed dilated pupils, patent ductus arteriosus, bulging (aneurysms) of the aorta and other arteries, blockage of arteries in the brain and lung, and abnormal intestines and bladder. Since this is a rare condition that was identified a few years ago by Dr. Dianna Milewicz, the Director of the John Ritter Research Program, and her colleagues, the medical community lacks much needed information on how the disease progresses and how to provide proper medical care for patients with this condition. There are no successful treatments available at this time. Shortly after Livie's diagnosis of MSMDS, the Olivia Petrera-Cohen Fund was established at UT Health to help change this.
Current Research Projects
Dr. Milewicz and her research group are working to define gene and mutation based precision medical care and treatment for those with MSMDS. Dr. Milewicz has brought together a worldwide consortium of experts in aortic and vascular diseases in the Montalcino Aortic Consortium (MAC) and started the process of collecting information from patients worldwide. The patients will be followed over several years and information collected on their health status and treatment to create medical guidelines for the best medical care for patients with MSMDS. The patients will also be provided information on any clinical trials that become available. Recently, using the data collected thus far from patients, The John Ritter Research Program held an informational webinar entitled, "Clinical History and Recommendations for Medical Management of Individuals with ACTA2 arginine 179 alterations" for people currently impacted by the disease and their medical team, which was a huge step in raising awareness.
To get to the point of defining the precise molecular defects that cause complications in patients, and to test therapies that would help with these complications, it is very important to study MSMDS in a mouse model of a disease specific change in ACTA2. This was a project that had been in the pipeline for quite some time but unfortunately efforts had been unsuccessful due to lack of funding. This is where Love for Livie has stepped in and provided all resources necessary for this project. We are proud to report that the complex genetic engineering for an inducible mouse model of the ACTA2 R179 genetic alteration is completed. These mice have their DNA engineered so that the mutation can be turned on in specific tissues and at specific times. The research team is currently in the process of examining and anlayzing the disease process in great detail through the affected mice and have recently had major breakthroughs! A potential treatment to prevent or delay the vascular disease in patients has been identified and clinical trials will be starting over the next 3-6 months!
Dr. Milewicz and her team have derived inducedpluripotent stem cells (iPSCs) from cells obtained from three individuals with an ACTA2 R179 (MSMDS) alteration. These iPSCs have been differentiated into smooth muscle cells to determine how the alteration disrupts the cells. ACTA2 encodes a protein called smooth muscle alpha-actin. They have identified a novel and critical function for this protein that is disrupted by altering arginine 179 and are actively conducting research related to this.
How You Can Help
Each year, Livie's family and the John Ritter Foundation for Aortic Health, a 501c3, team up to host a Benefit in NYC to raise money for ongoing research projects, advocacy & education. Please visit the Livie's Legacy tab to support our mission!
Watch below to hear Dr. Milewicz’s TEDx talk where she talks about children like Livie