Disease Focus: Autism
Functional genomics to study cellular convergence across ASD risk genes in neurodevelopment
Research Objective Our objective is to enable scalable genetic screening to study how neurogenesis is impacted by risk genes implicated in human psychiatric disorders. Impact We will develop and apply state-of-the-art genomic analysis to seek mechanisms and disease modifying solutions. Major Proposed Activities Identifying and validating efficient gRNA for gene editing Identify risk gene effects […]
Gene Therapy for SLC6A8 Creatine Transporter Disorder
Research Objective The objective is to define a final therapeutic candidate for an effective gene therapy for mutations of the creatine transporter SLC6A8, a major cause of X-linked intellectual disability (ID). Impact This disorder results in severe ID, autistic-like behavior, seizures, & lack or delay of speech with no treatment. Improving brain transduction is essential […]
A treatment for Rett syndrome using glial-restricted neural progenitor cells
Research Objective We developed a novel glial-restricted neural progenitor cells transplantation strategy as a treatment for Rett syndrome, reverting neuronal alterations caused by genetic mutations. Impact There are no disease-modifying therapies for Rett syndrome. Our therapeutic, if successful, will be a first-in-class treatment for this devastating neurological disorder and potentially others. Major Proposed Activities Characterization […]
Novel antisense therapy to treat genetic forms of neurodevelopmental disease.
Research Objective We propose to discovery and evaluate antisense gene therapy for specific mutations underlying debilitating or life-threatening neurodevelopmental diseases including epilepsy and autism syndromes. Impact The conditions are four specific neurodevelopmental syndromes where mutations are well suited to ASO therapy. The bottlenecks are current lack of cellular evidence for ASOs to impact disease course. […]
AAV9-Cas13 gene therapy for Angelman syndrome
Research Objective AAV9-Cas13 gene therapy for Angelman syndrome using a first-in-kind mechanism of action that will safely and permanently restore expression of endogenous UBE3A that is deficient in CNS neurons. Impact Angelman syndrome is a rare (1 in 15,000 births) neurogenetic disorder caused by loss of UBE3A in the brain, causing severe developmental delay, ataxia […]
Drug Development for Autism Spectrum Disorder Using Human Patient iPSCs
Research Objective We will use human patient induced pluripotent stem cell (hiPSC)-based models to screen for a drug that activates a transcription factor critical to the treatment of Autism Spectrum Disorder (ASD). Impact Our goal is to develop a small molecule to treat Autism Spectrum Disorder (ASD), which currently affects 1/68 children born in the […]
MSC delivery of an artificial transcription factor to the brain as a treatment for Angelman Syndrome
Research Objective Mesenchymal stem cells will be used to deliver an artificial transcription factor to neurons in the brain to treat a genetic disease. Impact It could lead directly to a treatment for Angelman Syndrome, but the approach could be used to alter gene expression in almost any brain disorder. It could overcome the brain […]
A drug-screening platform for autism spectrum disorders using human astrocytes
Autism spectrum disorders (ASD) are complex neurodevelopmental diseases that affect about 1% of children in the United States. Such diseases are mainly characterized by deficits in verbal communication, impaired social interaction, and limited and repetitive interests and behavior. The causes and best treatments remain uncertain. One of the major impediments to ASD research is the […]
Induced pluripotent stem cells from children with autism spectrum disorders
Autism spectrum disorders (ASD) are a family of disabling disorders of the developing brain that affect about 1% of the population. Studying the biology of these conditions has been difficult as they have been challenging to represent in animal models. The core symptoms of ASD, including deficits in social communication, imagination and curiosity are intrinsically […]
Studying neurotransmission of normal and diseased human ES cell-derived neurons in vivo
Stem cells, including human embryonic stem cells, provide extraordinary new opportunities to model human diseases and may serve as platforms for drug screening and validation. Especially with the ever-improving effective and safe methodologies to produce genetically identical human induced pluripotent stem cells (iPSCs), increasing number of patient-specific iPSCs will be generated, which will enormously facilitate […]