Disease-in-a-dish model of neuropsychiatric diseases for high-throughput therapeutic screening

This technology is an in vitro platform for assessing the role of epigenetic changes in neuropsychiatric diseases.

Unmet Need: Simple model of neurological disorders for screening therapeutic candidates

Aberrant epigenetic regulation has been implicated in a number of neuropsychiatric disorders, including schizophrenia, autism, amyotrophic lateral sclerosis, Parkinson’s disease, and Alzheimer’s disease. Despite the identification of genetic risk factors for such diseases, there is no definitive cure and most pharmacological interventions are ineffective. Thus, in order to identify and screen potential therapeutics, it is important to faithfully reproduce genetic and phenotypic aspects of the disease in simple and translational model systems.

The Technology: In vitro high-throughput therapeutic screening for neuropsychiatric disorders

This technology uses human induced pluripotent stem cells (hiPSC) with specific mutations in the SETD1A gene to model neuropsychiatric diseases. This gene encodes a histone methyltransferase, an epigenetic enzyme implicated in schizophrenia and related to other pathways underlying neurological disorders. This technology will enable high-throughput discovery of therapeutic candidates for neuropsychiatric diseases, identify biochemical pathways that may be involved in their pathology, and provide a more individualized approach to drug screening, potentially improving patient outcomes.

This technology has been validated using exome sequencing of schizophrenia patients and genetic mouse models with deficient SETD1A.

Applications:

• Drug screening for potential therapeutics pertaining to neuropsychiatric diseases
• Clinical and basic science research into genes that interact with SETD1A to alter schizophrenia phenotype
• Pharmacological intervention in disease-susceptible individuals during key developmental stages
• Analysis of SETD1A gene-environment interaction
• Studying gene therapy methods to modulate SETD1A mutations in neurons
• Assessment of drug side effects and tolerability in SETD1A-mutated tissues

Advantages:

• High-throughput platform for neurological drug screening
• Applicable to a variety of diseases associated with SETD1A mutations
• Cost-effective
• Can utilize a patient’s own cells for screening

Lead Inventor:

Joseph A. Gogos, M.D., Ph.D.

Related Publications:

• Mukai J, Cannavo E, Sun Z, Crabtree G, Diamantopoulou A, Thakur P, Chang CY, Cai Y, Lomvardas S, Takata A, Xu B. “Recapitulation and reversal of schizophrenia-related phenotypes in Setd1a-deficient mice” Neuron. 2019 Nov 6; 104(3): 471-487.

• Takata A, Ionita-Laza I, Gogos JA, Xu B, Karayiorgou M. “De novo synonymous mutations in regulatory elements contribute to the genetic etiology of autism and schizophrenia” Neuron. 2016 Mar 2; 89(5): 940-7.

• Takata A, Xu B, Ionita-Laza I, Roos JL, Gogos JA, Karayiorgou M. “Loss-of-function variants in schizophrenia risk and SETD1A as a candidate susceptibility gene” Neuron. 2014 May 21; 82(4): 773-80.

Tech Ventures Reference:

• IR CU20125

• Licensing Contact: Joan Martinez