ICOD for scientists

Project Summary

Down syndrome (DS) causes lifelong cognitive impairment, which results in important negative consequences for individuals, their families and society. Despite the heavy social burden and the greater medical needs linked to this intellectual disability, there is no approved therapy for DS-related cognitive impairment yet.

The ICOD project aims to address these unmet clinical needs by bringing into humans a first-in-class new drug (AEF0217) that targets the cannabinoid (CB1) receptor, whose hyperactivity has been recently linked to cognitive impairments in DS.1 AEF0217 belongs to a new pharmacological class, named “signaling specific inhibitors of the CB1 receptor (CB1-SSi)”, which reverses cognitive impairment in mouse models of DS.

The ICOD project will first complete Phase I human clinical trials with AEF0217 in healthy volunteers and DS subjects to assess its safety and tolerability.

The ICOD project aims to address these unmet clinical needs by bringing into humans a first-in-class new drug(AEF0217).

A multicenter, double-blind, placebo-controlled, randomized, parallel-group, Phase II dose finding study will be then conducted to assess the efficacy, safety and tolerability of AEF0217 in 128 young adults (18-35 years) with DS.

Cognitive function will be evaluated with the NIH Toolbox Cognitive Battery for Intellectual Disabilities. All subjects will benefit from a standardized cognitive training to reduce variance in care measures between patients.

The objectives of the ICOD project are:

  • To demonstrate that AEF0217 administered for 3 months improves cognitive performance in male and female individuals with DS.
  • To assess the effects of AEF0217 on a patient's reported outcome in health related quality of life and adaptive functionality.
  • To assess the duration of AEF0217 effects after treatment discontinuation.
  • To assess the safety and tolerability of AEF0217.

1. Navarro-Romero A, Vázquez-Oliver A, Gomis-González M, Garzón-Montesinos C, Falcón-Moya R, Pastor A, Martín-García E, Pizarro N, Busquets-Garcia A, Revest JM, Piazza PV, Bosch F, Dierssen M, de la Torre R, Rodríguez-Moreno A, Maldonado R, Ozaita A. Cannabinoid type-1 receptor blockade restores neurological phenotypes in two models for Down syndrome. Neurobiol Dis. 2019 May;125:92-106