Pathophysiological mechanisms of autism spectrum disorder (ASD) and neurodegenerative disease: development of biomarkers and therapeutics

  • Park, Yongsoo (Lead Principal Investigator)
  • Da’as, Dr.Sahar (Principal Investigator)

Project: Experimental Development/Translation Research

Project Details

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder, characterized by repetitive behaviors and deficits in reciprocal social interaction and communication. An increasing number of genetic variants implicated in ASD has been reported so far, suggesting a high degree of locus heterogeneity and a contribution from rare and de novo variants. ASD is phenotypically and etiologically so heterogeneous that it is challenging to determine a contributing role of various variants on ASD etiology and to uncover the underlying genetic, pathologic, and cellular pathophysiology. It is why the functional study of genetic variants associated with ASD is critical for the elucidation of ASD pathophysiology and we have to move from gene discovery to understanding the biological influences of genetic mutations and variants for the development of ASD therapeutics. Risk variants associated with ASD converge on calcium signaling and can cause the defect in calcium signaling of neurons. We aim to study the pathophysiological mechanisms underlying ASD phenotype using patient?specific human induced pluripotent stem cell (hiPSC)?derived cortical neurons and brain organoids with focus on calcium signaling. The molecular biomarkers for ASD diagnosis are also lacking. Early intervention and detection are critical to help ASD children effectively improve their language ability and social interaction. Because exosomes cross the blood-brain barrier (BBB), exosome RNA/proteins are considered as good biomarkers for different types of diseases including cancer, cardiovascular diseases, Alzheimer’s disease (AD) and Parkinson's disease (PD). Exosomes are small vesicles with 40–150 nm in diameter and are considered as the carriers of signaling macromolecules and RNAs for cell-cell communication. I hypothesize that exosome carries ASD-specific RNA/proteins that reflect the severity of ASD. Therefore, by applying genomics and proteomics approach I believe to identify ASD-specific biomarkers that originate from exosome in blood samples of ASD individuals in Qatar. The goal of this project is to identify and validate a list of molecular biomarkers for early diagnosis of ASD.

Submitting Institute Name

Hamad Bin Khalifa University (HBKU)
Sponsor's Award NumberIGP5-2022-001
Proposal IDQBRI-CORE-000004
StatusActive
Effective start/end date1/01/2331/12/25

Collaborative partners

Primary Theme

  • Precision Health

Primary Subtheme

  • PH - Diagnosis Treatment

Secondary Theme

  • None

Secondary Subtheme

  • None

Keywords

  • Autism spectrum disorder (ASD), Neurodevelopmental disorders, Human induced pluripotent stem cell (hiPSC), Biomarkers, Exosomes, Blood-brain barrier
  • None

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