2. Academic Validation
  3. Characterization of a Clinically and Biologically Defined Subgroup of Patients with Autism Spectrum Disorder and Identification of a Tailored Combination Treatment

Characterization of a Clinically and Biologically Defined Subgroup of Patients with Autism Spectrum Disorder and Identification of a Tailored Combination Treatment

  • Biomedicines. 2024 Apr 30;12(5):991. doi: 10.3390/biomedicines12050991.
Laura Pérez-Cano 1,  Luigi Boccuto 2 3,  Francesco Sirci 1,  Jose Manuel Hidalgo 1,  Samuel Valentini 1,  Mattia Bosio 1,  Xavier Liogier D'Ardhuy 4,  Cindy Skinner 2,  Lauren Cascio 2 5,  Sujata Srikanth 2 5,  Kelly Jones 2 5,  Caroline B Buchanan 2,  Steven A Skinner 2,  Baltazar Gomez-Mancilla 4 6,  Jean-Marc Hyvelin 4,  Emre Guney 1,  Lynn Durham 1 4
Affiliations

Affiliations

  • 1 Discovery and Data Science (DDS) Unit, STALICLA SL, Moll de Barcelona, s/n, Edif Este, 08039 Barcelona, Spain.
  • 2 JC Self Research Institute, Greenwood Genetic Center, Greenwood, SC 29649, USA.
  • 3 Healthcare Genetics and Genomics, School of Nursing, Clemson University, Clemson, SC 29634, USA.
  • 4 Drug Development Unit (DDU), STALICLA SA, Avenue de Sécheron 15, 1202 Geneva, Switzerland.
  • 5 Research and Education in Disease Diagnosis and Interventions (REDDI) Lab, Center for Innovative Medical Devices and Sensors (CIMeDS), Clemson University, Clemson, SC 29634, USA.
  • 6 Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A 0G4, Canada.
PMID: 38790952 DOI: 10.3390/biomedicines12050991
Abstract

Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders (NDDs) with a high unmet medical need. The diagnosis of ASD is currently based on behavior criteria, which overlooks the diversity of genetic, neurophysiological, and clinical manifestations. Failure to acknowledge such heterogeneity has hindered the development of efficient drug treatments for ASD and Other NDDs. DEPI® (Databased Endophenotyping Patient Identification) is a systems biology, multi-omics, and machine learning-driven platform enabling the identification of subgroups of patients with NDDs and the development of patient-tailored treatments. In this study, we provide evidence for the validation of a first clinically and biologically defined subgroup of patients with ASD identified by DEPI, ASD Phenotype 1 (ASD-Phen1). Among 313 screened patients with idiopathic ASD, the prevalence of ASD-Phen1 was observed to be ~24% in 84 patients who qualified to be enrolled in the study. Metabolic and transcriptomic alterations differentiating patients with ASD-Phen1 were consistent with an over-activation of NF-κB and NRF2 transcription factors, as predicted by DEPI. Finally, the suitability of STP1 combination treatment to revert such observed molecular alterations in patients with ASD-Phen1 was determined. Overall, our results support the development of precision medicine-based treatments for patients diagnosed with ASD.

Keywords

ASD Phenotype 1; DEPI; NF-κB; NRF2; STP1 tailored treatment; Warburg effect; cAMP; metabolic and transcriptomic alterations; precision medicine.

Figures
Products