The rare disease is caused by the mutation of one of the top risk genes for autism spectrum disorder.
A team of researchers is pursuing a study to better understand the biology of activity-dependent neuroprotective protein (ADNP) syndrome, a rare neurodevelopmental disorder that affects brain formation, function, and development.
ADNP syndrome, formerly known as Helsmoortel-Van der Aa Syndrome, has been a documented cause of autism spectrum disorders (ASD), along with other behavioral disorders and cognitive difficulties. Researchers from the Seaver Autism Center for Research and Treatment, from the Icahn School of Medicine at Mount Sinai, plan to enroll approximately 50 patients for a comprehensive characterization study.
Not much of the disease’s makeup has been uncovered since it was first described in 2014, Silvia De Rubeis, PhD, assistant professor, Department of Psychiatry at Icahn, told MD Magazine. What is known is that the clinical phenotype is very complex — capable of causing cardiovascular, endocrine, immune, gastrointestinal, musculoskeletal, and sensory co-morbidities.
“We need to characterize systematically a larger cohort of patients to get a comprehensive clinical picture and identify objective clinical measures that can be used at the beginning and at the end of a clinical trial to assess efficacy,” Rubeis said. “And for the same purpose, we are in urgent need of biomarkers, ideally translatable across pre-clinical models and patients.”
The intent of a profile and biomarkers is to establish clinical targets and a stronger perspective of potential treatment outcome measures, which could then shape future clinical trials. Patients with ADNP syndrome will be recruited for a 3-day assessment, which will include:
Researchers will also collect blood cells from patients and their participating family members, to be induced into pluripotent stem cells and reprogrammed in nerve cells. The hope is to better understand the syndrome’s neurobiology, and to use the samples to test novel therapeutics.
Because of ADNP syndrome’s complex clinical phenotype, researchers will also confer with clinicians from other specialties to capture other medical comorbidities in their findings. There’s expectation that findings may have further implications for other ASD-related conditions.
“We have and are applying this genetics-first translational approach to other disorders associated to autism and intellectual disability, for example Phelan-McDermid syndrome and FOXP1 syndrome,” Rubeis said.
In just recent years’ large-scale genomic analyses, ADNP has been uncovered as one of the top risk genes for ASD, Rubeis said. The spectrum disorder has been a consistent behavioral problem associated with ADNP syndrome, having far-reaching impact on patients and their families.
“In our clinical study, we will use gold-standard diagnostic tools for ASD to examine the nature and severity of ASD symptoms in individuals with ADNP syndrome,” Rubeis said. “This will beneficial for individuals with ADNP mutations and their families because it will inform clinical care and guide appropriate intervention, especially early in development.”
Despite its connection to ASD and various co-morbidities, researchers noted they will be at odds in finding funding for research into a rare genetic condition such as ADNP syndrome. With $200,000 committed to enrolling the first 10 patients in year 1, the Seaver Autism Center is still seeking $1.8 million in funding to reach the 50-participant study goal.