Dr. Gerarda Cappuccio named as the co-recipient of the 2022 John M. Opitz Young Investigator Award

A pediatrician, Dr. Cappuccio is currently pursuing a postdoctoral fellowship in the laboratory of Dr. Mirjana Maletic-Savatic, associate professor at Baylor and Duncan NRI investigator, and is co-mentored by Dr. Huda Zoghbi, distinguished service Professor at Baylor and director of the Duncan NRI.

“Dr. Cappuccio’s drive and scholarship combined with her passion for understanding and treating genetic disorders made her richly deserving of the 2022 John M. Opitz Young Investigator Award,” said Dr. Zoghbi, who is also a Howard Hughes Medical Institute investigator.

The John M. Opitz Young Investigator Award was established by Wiley publishing company in 2001 to honor the Founder and first Editor-in-Chief of the American Journal of Medical Genetics. For two decades, this award has recognized the junior investigator author of the most significant scientific paper published in the journal in the previous year. The award-winning paper is carefully chosen by stringent criteria by a committee of leaders in medical genetics and must cover one of the following areas of research - congenital anomalies, mechanisms of morphogenesis, developmental biology, or genes involved in development - all areas that are central to the legacy of Dr. John Opitz. Moreover, candidates selected for the annual award should be under the age of 40 years, or within 10 years of completing postdoctoral training.

Dr. Cappuccio’s award-winning paper entitled “A pilot clinical trial with losartan in Myhre syndrome", describes the research she performed for her graduate thesis under the guidance of Dr. Nicola Brunetti-Pierri at the Telethon Institute of Genetics and Medicine in Italy.

In this study, Dr. Cappuccio and others tested the effectiveness of the drug losartan in treating certain symptoms in patients with an ultrarare genetically-inherited connective tissue disorder called the “Myhre syndrome”, characterized by skeletal abnormalities and chronic hardening of the skin and connective tissues. Patients suffering from this progressive condition have a short stature, limited joint mobility, distorted facial features, deafness, intellectual and behavioral problems, and could have life-threatening complications.

The Myhre syndrome is caused by gain-of-function variants in the SMAD4 gene that encodes a protein involved in the bone morphogenetic pathway and the transforming growth factor (TGF)-β pathway. This results in a disruption of the molecular glue, the extracellular matrix, which comprises of a large network of proteins and molecules that surround, support, and give structure to the cells and tissues in the body.

Currently, losartan is used clinically to treat high blood pressure and reduce the risk of stroke in patients with high blood pressure and an enlarged heart. However, studies suggested that it can reduce TGF-β-mediated fibrosis and improve connective tissue abnormalities, which prompted Dr. Cappuccio to test its effectiveness in treating the symptoms of Myhre syndrome. She found that a year-long losartan treatment improved clinical scores of skin, joint, and heart fibrosis in a pilot cohort of four patients. The results from this study are very promising and set the stage for a larger clinical trial for this treatment to receive FDA approval.

“Currently, Dr. Cappuccio is leveraging her clinical background and translational research experience to investigate the mechanisms of pathogenesis and to identify treatments for other rare diseases,” Dr. Maletic-Savatic said. “She uses human models of disease, derived from patient’s own skin cells. She generates brain organoids (popularly called ‘mini-brains’), which are tiny, self-organized three-dimensional individualized tissues that replicate early human brain development. She then uses these as tools to study various pathways involved in rare neurological disorders such as Rett syndrome and MECP2 duplication syndrome as well as to test how these pathways are modulated in response to different treatments. I am not surprised that Gerarda received the 2022 John M. Opitz Young Investigator Award - she fully deserves it. I consider myself fortunate to have her in my lab and at the Duncan NRI - where we train and foster young physicians and scientists such as Gerarda to become future leaders in translational medicine.”

“As a pediatrician, I am motivated by the promise of translational and preclinical discovery in finding new treatments for patients with untreatable genetic conditions,” Dr. Cappuccio said. “I am extremely thankful to the American Journal for Medical Genetics for recognizing and supporting the efforts and contributions of young investigators like me and grateful to Drs. Zoghbi and Maletic-Savatic for their excellent mentorship.”