TY - JOUR
T1 - Drug repurposing candidates to treat core symptoms in autism spectrum disorder
AU - Koch, Elise
AU - Demontis, Ditte
N1 - Publisher Copyright:
Copyright © 2022 Koch and Demontis.
PY - 2022/9
Y1 - 2022/9
N2 - Autism spectrum disorder (ASD) is characterized by high heritability and clinical heterogeneity. The main core symptoms are social communication deficits. There are no medications approved for the treatment of these symptoms, and medications used to treat non-specific symptoms have serious side effects. To identify potential drugs for repurposing to effectively treat ASD core symptoms, we studied ASD risk genes within networks of protein-protein interactions of gene products. We first defined an ASD network from network-based analyses, and identified approved drugs known to interact with proteins within this network. Thereafter, we evaluated if these drugs can change ASD-associated gene expression perturbations in genes in the ASD network. This was done by analyses of drug-induced versus ASD-associated gene expression, where opposite gene expression perturbations in drug versus ASD indicate that the drug could counteract ASD-associated perturbations. Four drugs showing significant (p < 0.05) opposite gene expression perturbations in drug versus ASD were identified: Loperamide, bromocriptine, drospirenone, and progesterone. These drugs act on ASD-related biological systems, indicating that these drugs could effectively treat ASD core symptoms. Based on our bioinformatics analyses of ASD genetics, we shortlist potential drug repurposing candidates that warrant clinical translation to treat core symptoms in ASD.
AB - Autism spectrum disorder (ASD) is characterized by high heritability and clinical heterogeneity. The main core symptoms are social communication deficits. There are no medications approved for the treatment of these symptoms, and medications used to treat non-specific symptoms have serious side effects. To identify potential drugs for repurposing to effectively treat ASD core symptoms, we studied ASD risk genes within networks of protein-protein interactions of gene products. We first defined an ASD network from network-based analyses, and identified approved drugs known to interact with proteins within this network. Thereafter, we evaluated if these drugs can change ASD-associated gene expression perturbations in genes in the ASD network. This was done by analyses of drug-induced versus ASD-associated gene expression, where opposite gene expression perturbations in drug versus ASD indicate that the drug could counteract ASD-associated perturbations. Four drugs showing significant (p < 0.05) opposite gene expression perturbations in drug versus ASD were identified: Loperamide, bromocriptine, drospirenone, and progesterone. These drugs act on ASD-related biological systems, indicating that these drugs could effectively treat ASD core symptoms. Based on our bioinformatics analyses of ASD genetics, we shortlist potential drug repurposing candidates that warrant clinical translation to treat core symptoms in ASD.
KW - autism spectrum disorder
KW - drug repurposing
KW - genetics
KW - network medicine
KW - protein-protein interactome
UR - http://www.scopus.com/inward/record.url?scp=85139069978&partnerID=8YFLogxK
U2 - 10.3389/fphar.2022.995439
DO - 10.3389/fphar.2022.995439
M3 - Journal article
C2 - 36172193
AN - SCOPUS:85139069978
SN - 1663-9812
VL - 13
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 995439
ER -