Genes-First Approach to Precision Medicine in Autism

These studies work towards developing an international registry for Christianson Syndrome, developing convergence across genetic subtypes and using precision medicine in autism clinics. 

 

Current Projects and Future Goals

We have developed an international registry for the disorder termed Christianson syndrome, caused by genetic mutations in the gene NHE6 on the X-chromosome in boys. At present, we have enrolled approximately 40 families internationally which now extends across 14 countries and is the largest cohort of families with this condition. Through this work we have developed stem cells as an experimental platform in the laboratory to screen candidate therapeutics. The first candidate therapeutic screen on the stem cells of affecting children is nearly at the completion stage. 

We are working to generalize the neuro developmental mechanisms in specific genetic subtypes of autism across different, related gene mutations. Genetic conditions such as Christianson syndrome and Angelman syndrome, are clearly related at the level of patient symptom. We are thus investigating mechanistic linkages with patient-cells in the laboratory. Our recent discoveries include abnormalities in mitochondrial function, the major energy source in cells, in postmortem brain tissue from people with autism. We are seeking convergence around mitochondrial mechanisms. 

With the support of Bradley Hospital, Dr. Daniel Moreno De Luca established the Genetic Psychiatry Consultation Service, a specialty program that is part of the Verrecchia Clinic for Children with Autism and Developmental Disabilities. This service focuses on evaluating and providing medical and psychiatric treatment recommendations for children and adults with autism and developmental disabilities who have had genetic testing that revealed an abnormal result, using those results to inform clinical care. In parallel, Dr. Moreno De Luca also established and streamlined the process to offer genetic testing to people with autism and developmental disabilities at who receive outpatient care at Bradley Hospital, considered the standard of care for this population and recommended by many medical professional societies.

Although genetic testing is recommended as the standard of care for people with autism and developmental disabilities, it is only occurring in the minority of patients. Through his Precision Medicine in Autism (PRISMA) study, Dr. Moreno De Luca is working on identifying barriers and opportunities around genetic testing for autism through a survey titled “Attitudes, Perspectives, and Results of Genetic Testing in Autism Disorders” that is designed to assess knowledge and expectations from genetics testing within the context of autism treatment, and which has been developed in English and Spanish to capture a wide and inclusive perspective. Over 200 families and people with ASD from RICART have already made their voices heard, and we are in the process of analyzing the results and expect to apply what we learn from them to enhance clinical care for autism in R.