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DRUG-GENE EXPRESSION PROFILES AND SYSTEMS BIOLOGY APPROACH TO IDENTIFY REPURPOSED DRUG CANDIDATES FOR TARGETING SCLEROSTIN IN PERI-IMPLANTITIS DISEASE.

DRUG-GENE EXPRESSION PROFILES AND SYSTEMS BIOLOGY APPROACH TO IDENTIFY REPURPOSED DRUG CANDIDATES FOR TARGETING SCLEROSTIN IN PERI-IMPLANTITIS DISEASE.

Dr.Pradeep Kumar Yadalam

Successful identification of a therapeutic strategy to treat patients with periimplantitis remains extremely important as post-implant bone degradation leads to implant failure and extreme bone loss. Given that the establishment of a new drug is quite expensive and time-consuming, the drug repurposing approach has come in handy. It helps to identify the experimental drugs that are beyond the purview of the initial clinical indication. In our current study, we propose a three-step drug repurposing approach in treating peri-implant bone defects and investigating the action of the FDA approved drugs to inhibit the key protein Sclerostin, involved in bone degradation. As the preliminary step, we differentiated the gene expression pattern in periimplantitis and dentate patients with their drug-induced profiles to identify the primary lead candidates. As the second step, we employed the computational biology approach to evaluate the protein-drug interaction and segregate the best hits among the identified lead compounds for sclerostin. Finally, the mode of action network for each candidate is established with the help of literature support, and the drug enrichment and pathway analysis are performed on the target genes in the network to evaluate the drug efficacy. This approach provided us with a drug interaction profile and specific genes and biomarkers to target bone mineralization in peri-implantitis. Thus, our three-step drug repurposing method is consistent with identifying the drug molecules with high efficacy and developing an efficient therapeutic strategy to treat peri-implantitis.