Principal Investigator: Prof. Imed Gallouzi

Poster Presenter: Shahryar Khattak

Lab:

iPSC based disease models in a dish: Deciphering Autism Spectrum Disorder (ASD) and Alzheimer's Disease (AD) in Saudi population

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by restricted, repetitive behavior and deficits in social interaction and communication skills. It is a heterogeneous condition with variable degrees of severity and it is often combined with comorbid conditions such as intellectual disability, sleep disorders, anxiety and epilepsy.

Alzheimer's Disease (AD) is a complex neurodegenerative disorder characterized by increase of neurofibrillary tangle and amyloid plaques in the brain. Neurofibrillary tangles are aggregates of hyperphosphorylated tau protein while amyloid plaques are clumps of amyloid-β peptides. Despite the extensive research on AD, the causative relationship between amyloid-β and tau pathologies in humans is unknown.

Past studies investigating the genetic causes of ASD and AD have not included Saudi patient cohorts. The different Saudi ethnic groups have a distinct genetic makeup and it is not known what kinds of mutations drive the disease in the Saudi population; a closed community with high consanguineous marriage rates, it is imperative to investigate the genetic causes and molecular mechanisms of ASD and AD in the Saudi population.

We have established a collaboration with Taif University who has recruited and obtained blood samples from more than 105 Saudi ASD individuals. Whole genomic sequencing is being performed on these samples to identify clinically relevant ASD mutations. We will generate ASD specific iPSC lines and further differentiate them to cortical neurons and brain organoids to study the ASD phenotype in the dish. Similarly, we have signed a collaboration agreement with King Faisal specialist hospital and research center to obtain AD patient samples from Saudi population. After whole exome sequencing and identification of AD causative mutations, we will generate AD specific iPSC lines and directly differentiate them to cortical neurons and brain organoids to develop AD-specific models in a dish.