An Intellectual Development Disorder (IDD) is a cognitive skills development disorder beginning in early childhood. Despite advances in genetics, in around 50% of cases the cause of this neurodevelopmental disorder is still not identified. The ENCode-ID project, led by Dr. Laïla el-Khattabi within Professor. Bassem Hassan’s team, and in collaboration with the AP-HP/Sorbonne University (Armand Trousseau and Pitié-Salpêtrière hospitals) clinical and biological genetics teams, as well as Lille and Rennes teaching hospitals, has received public health sponsorship support from Mutuelles AXA, as part of the second call for projects launched in February 2023.The aim of ENCode-ID is to identify new genetic causes, severity biomarkers, as well as new therapeutic pathways.
Delayed neurodevelopment can manifest itself in many different ways at an early age, including delayed language development, toilet training, delays in learning to read, etc. When neurodevelopmental milestones are not met at the same age as other children, it is possible that a child may have an Intellectual Development Disorder (IDD). This disorder, which varies in its severity, affects between 1% and 2% of the population. The impact on the child and their family make this a major public health issue.
GENETIC DIAGNOSIS CRUCIAL TO TREATING INTELLECTUAL DEVELOPMENTAL DISORDERS
The genetic factors responsible for IDDs are manifold and heterogeneous, making them difficult to
diagnose.Significant technological progress in recent years has substantially increased diagnostic yield, up from 5% a decade ago to 50% today. Although this increase is remarkable, it is still not enough – half of all patients affected by an IDD are still undiagnosed. However, several studies emphasize the positive impact of diagnosis on care, acceptance of the pathology, removing parents’ guilt, and avoiding misdiagnosis.
Genetic diagnosis will therefore be one of the major challenges for intellectual development disorders in the coming years.
EXPLORING THE NON-CODING GENOME TO IMPROVE DIAGNOSIS OF INTELLECTUAL DEVELOPMENT DISORDERS
The ENCode-ID translational medical research project conducted at Paris Brain Instituteby Dr. Laïla El-Khattabi aims to improve IDDs diagnosis rates by exploring the role of genetic variants in non-coding genome sequences. This work should have an immediate impact on patients and their families, particularly for their care and genetic counseling.In addition, the work will generate a considerable amount of data that can be used by the teams at Paris Brain Institute and by the international community.
Dr. Laïla El-Khattabi
ENCode-ID is the first study to propose a comprehensive approach to large-scale functional studies of mutations in non-coding regulatory genomic regions. The project is not just innovative in its approach, but also innovative in the techniques it deploys: multiplex genome editing, use of brain organoids as a model, single cell analysis techniques and innovative bioinformatics tools.
In addition, this is currently the only study to propose in silico exploration of therapeutic pathways for an IDD in a model that closely mimics early brain development in humans, using an algorithm for restoring altered developmental trajectories. This is all made possible through the advanced skills of the lead team, the collaboration with leading clinical teams specializing in this type of disorder, and Paris Brain Institute’s unique expertise and core technological and bioinformatics facilities.
THE INNOVATIVE HOLISTIC APPROACH OF THE ENCODE-ID PROJECT, SUPPORTED BY MUTUELLES AXA’S MUTUAL
The ENCode-ID project has successfully secured the support of Mutuelles AXA and will receive healthcare patronage funding over two years, as part of its program dedicated to supporting innovative research initiatives in France.
The healthcare patronage program launched by Mutuelles AXA in early 2022 is a new commitment that complements its traditional patronage focus areas in support of social, environmental and national heritage causes.
Paris Brain Institute and its teams wish to thank Mutuelles AXA for its continued support.