Projects
Characterization of genetic landscape of ID and CP
Gene/Variant Discovery for CP
- Status
- ongoing
- Rationale
- Cerebral palsy (CP) is the most common childhood-onset motor disability. A diverse set of risk factors contributes to CP. In approximately 20% of cases, there are no clear perinatal risk factors, suggesting the possibility of an underlying genetic disorder. Understanding the genetic landscape of CP has implications for diagnosis as well as treatment.
- Description
- In this project, we are using genome sequencing to discover genetic disorders presenting as cerebral palsy, in instances where there are known acquired risk factors for CP, as well as those where there are no acquired risk factors for CP.
- Acknowledgments
This study is part of the Children’s Rare Disease Cohorts (CRDC) Initiative, supporting gene discovery for different disease cohorts.
- Contact
- sophia.kim@childrens.harvard.edu
Characterization of specific neurodevelopmental deficits in genetic NDDs
Circadian Biology of EHMT1 and Sleep-Related Neurodevelopmental Collapse in Kleefstra Syndrome
- Status
- ongoing
- Rationale
- Kleefstra Syndrome (KLEFS1) is a complex neurodevelopmental genetic syndrome characterized by a high prevalence of autism and intellectual disability, as well as severe neuropsychiatric illness. The latter can include severe insomnia, psychosis, catatonia, bipolar disorder, obsessive compulsive disorder, and/or developmental regression. The neuropsychiatric illness in KLEFS1 represents a significant concern for affected families and represents a priority area for intervention. Notably, there is some limited data suggesting that use of certain antipsychotics, including olanzapine, may potentially restore functioning in individuals with KLEFS1 who have experienced insomnia, psychosis, and developmental regression.
- Description
- In this project, we are studying the relationship between sleep and neurospychiatric illness in individuals with KLEFS1, pairing functional studies of EHMT1 biology using patient-derived fibroblasts with standardized neurodevelopmental assessments, standardized sleep assessments, and Fitbit-based actigrapahy.
- Funding Sources
- Acknowledgments
This study is a joint collaboration with the lab of Jonathan Lipton, focused on circadian biology in neurodevelopmental disorders, and the lab of Joe Kossowsky, focused on health information from wearable devices.
Development of targeted therapeutics for genetic NDDs
JAG201 Gene Therapy Study in Children & Adults With SHANK3 Haploinsufficiency
- Status
- ongoing
- Description
- This is a Phase 1/2, first in human, open-label, dose-escalation study to evaluate the safety, tolerability, and clinical activity of a single dose of JAG201 administered via intracerebroventricular (ICV) injection in pediatric and adult participants with SHANK3 haploinsufficiency resulting from SHANK3 loss of function mutations and chromosomal deletions encompassing the SHANK3 gene.
- ClinicalTrials.Gov
- Contact
- anna.cronin@childrens.harvard.edu
sydney.klau@childrens.harvard.edu
A Study of NNZ-2591 in Pediatric Participants With Phelan-McDermid Syndrome
- Status
- ongoing
- Description
- This Phase 3, randomized, double-blind, parallel-group (2-arm), placebo-controlled, multicenter study will evaluate the efficacy and safety of NNZ-2591 compared to placebo in pediatric participants with Phelan- McDermid Syndrome.
- ClinicalTrials.Gov
- Contact
- asli.sahin@childrens.harvard.edu
Clinical practice changes regarding genetic testing for NDDs
Defining the Role of Genetic Testing in the Diagnostic Workup of Cerebral Palsy
- Status
- ongoing
- Description
- We are carrying out a comparative effectiveness study to measure the effectiveness and impact of three testing approaches in CP: (1) brain MRI alone, (2) brain MRI plus ES, and (3) brain MRI plus GS. Our long-term goal is to provide doctors and families with evidence to guide decision-making, reduce confusion, and help update official medical society practice guidelines for diagnostic testing for CP.
- Funding Sources
- Contact
- Erica.Kwiatkowski@childrens.harvard.edu
Cecilia.Doherty@childrens.harvard.edu