Mount Sinai Study to Characterize Rare Neurodevelopmental Disorder Tied to Autism
Researchers seek to transform understanding of and inform precision treatment approaches to newly identified syndrome
A research team from The Seaver Autism Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai is leading a new study that aims to understand the biology of ADNP syndrome, a rare neurodevelopmental disorder caused by a mutation in the ADNP (activity-dependent neuroprotective protein) gene. This important gene affects brain formation and development, as well as brain function. The ADNP gene also affects other organs and functions of the body.
First reported in 2014, ADNP syndrome (also known as Helsmoortel-van der Aa syndrome) is a serious condition that can cause problems with neurological, cardiovascular, endocrine, immune, musculoskeletal, and gastrointestinal systems, as well as vision, hearing, growth, feeding, and sleep. It can also cause mild to severe cognitive difficulties and delays in speech and motor abilities. It causes behavioral disorders, including autism spectrum disorders (ASD), in a substantial proportion of cases. ADNP mutations are thought to be among the more common single-gene causes of ASD, but the full extent of ADNP syndrome is unknown, leaving patients, their families, and experts in the field in great need of a breakthrough. There is currently no cure and no FDA-approved treatment for ADNP syndrome.
The new research study seeks to enroll approximately 50 patients (10 within the first year) to comprehensively characterize the ADNP syndrome phenotype while investigating the neurobiological pathways that underlie ADNP syndrome through stem cell and animal studies.
“This study will significantly advance our understanding of ADNP syndrome to help guide our clinical practices with patients and to provide a foundation for the development of novel therapeutics in the future,” says Joseph D. Buxbuam, PhD, Director of The Seaver Autism Center for Research and Treatment at Mount Sinai. “This deeper understanding of a rare, single-gene cause of autism not only provides desperately needed insight for ADNP patients and their families, but will also serve as a window to our understanding of the broader mechanisms of ASD and other neurodevelopmental disorders.”
The Mount Sinai research team expects to define a clinical profile and biological markers (objective tests that accurately and reliably measure specific biological processes associated with a specific neurodevelopmental disorder) of ADNP syndrome. The resulting profile and biomarkers will establish clinical targets and appropriate outcome measures for use in clinical trials. Future studies can then use the identified biomarkers to predict and evaluate treatment response. The team will recruit individuals with ADNP syndrome and their families for a deep and detailed assessment that takes place over three days and includes a clinical evaluation of intellectual and adaptive functioning; expressive and receptive language; gross, fine and visual motor function sensory processing; and electrophysiology and eye tracking, as well as a medical and psychiatric history, neurological evaluation, ASD symptomatology, medical record review, magnetic resonance imaging, and electroencephalogram. All data will be shared with the larger ADNP academic community and the team will establish a cohort of families, laying the foundation for future clinical trials.
During the evaluation, the team will collect blood cells from affected patients and family members. These blood cells will be induced into pluripotent stem cells and reprogrammed into nerve cells to better understand the neurobiology of the disease and to test novel therapeutics. The Mount Sinai team will also partner with groups working with genetically modified mouse models of ADNP syndrome to gain additional insights in the neurobiology of ADNP syndrome, to develop translational electrophysiological biomarkers in the animals, and to compare the impact of test compounds on human neurons in vitro (in the lab) and in animals in vivo (in living subject).
Similar research conducted at The Seaver Autism Center has significantly advanced understanding of other rare ASD-associated genetic disorders, including Phelan-McDermid syndrome and FOXP1 syndrome, aiding in the pursuit of novel therapeutics.
This new ADNP syndrome study has the potential to impact thousands of individuals with neurodevelopmental disorders. However, large grant-making institutions like the National Institutes of Health (NIH) do not commonly support early avenues of pre-clinical and clinical research for extremely rare genetic conditions, so finding funding for this critical study is difficult. A $200,000 donation will enable Mount Sinai to enroll the first 10 patients during year one. The Seaver Autism Center is seeking philanthropic partners to help fund an additional $1.8 million necessary to study a statistically significant total of 50 study participants.
For more information about the study, please visit: http://icahn.mssm.edu/research/seaver/events or call 212-241-0961.
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai is a national and international source of unrivaled education, translational research and discovery, and collaborative clinical leadership ensuring that we deliver the highest quality care—from prevention to treatment of the most serious and complex human diseases. The Health System includes more than 7,200 physicians and features a robust and continually expanding network of multispecialty services, including more than 400 ambulatory practice locations throughout the five boroughs of New York City, Westchester, and Long Island. The Mount Sinai Hospital is ranked No. 14 on U.S. News & World Report's "Honor Roll" of the Top 20 Best Hospitals in the country and the Icahn School of Medicine as one of the Top 20 Best Medical Schools in country. Mount Sinai Health System hospitals are consistently ranked regionally by specialty and our physicians in the top 1% of all physicians nationally by U.S. News & World Report.