Using Advanced Bioinformatics Tools to Identify Novel Therapeutic Candidates for Age-Related Macular Degeneration

Abstract

Purpose Age-related macular degeneration (AMD) is the most common cause of aging-related blindness in the developing world. Although medications can slow progressive wet AMD, currently, no drugs to treat dry-AMD are available. We use a systems or in silico biology analysis to identify chemicals and drugs approved by the Food and Drug Administration for other indications that can be used to treat and prevent AMD. Methods We queried National Center for Biotechnology Information to identify genes associated with AMD, wet AMD, dry AMD, intermediate AMD, and geographic atrophy to date. We combined genes from various AMD subtypes to reflect distinct stages of disease. Enrichment analysis using the ToppGene platform predicted molecules that can influence AMD genes. Compounds without clinical indications or with deleterious effects were manually filtered. Results We identified several drug/chemical classes that can affect multiple genes involved in AMD. The drugs predicted from this analysis include antidiabetics, lipid-lowering agents, and antioxidants, which could theoretically be repurposed for AMD. Metformin was identified as the drug with the strongest association with wet AMD genes and is among the top candidates in all dry AMD subtypes. Curcumin, statins, and antioxidants are also among the top drugs correlating with AMD-risk genes. Conclusions We use a systematic computational process to discover potential therapeutic targets for AMD. Our systematic and unbiased approach can be used to guide targeted preclinical/clinical studies for AMD and other ocular diseases. Translational Relevance Advanced bioinformatics models identify novel chemicals and approved drug candidates that can be efficacious for different subtypes of AMD.

Association of metformin use with risk of newly onset neovascular age-related macular degeneration development

“…This study found that of the 77,146 drugs queried, metformin was the 1st potential drug candidate for wet AMD-related genes, 13th for dry AMD-related genes, and 21st for all AMD-related genes. 21 Therefore, it may have promise as a drug candidate for the prevention of AMD and nAMD, especially as it is an food and drug administration (FDA)-approved treatment for Type 2 diabetes and has few side effects. 20 In addition, it has been used safely without causing hypoglycemia and offers a similarly favorable safety profile in the treatment of other conditions, including polycystic ovarian syndrome, prediabetes, and obesity, and is being studied in others, including cardiovascular disease, malignancy, and age-related dementia.…”

Repurposing medications for treatment of age-related macular degeneration: Insights from novel approaches to data mining

“…Nadeem et al 82 used advanced bioinformatics modeling to identify drug classes that affect the genes integral to AMD pathogenesis. This was the first time a systems medicine approach was used to predict drugs for AMD treatment.…”

Elevated Intraocular Pressure and Glaucomatous Optic Neuropathy: Genes to Disease Mechanisms, Therapeutic Drugs, and Gene Therapies

“…Indeed gene product networks and gene interactions powerfully impact disease initiation and progression, and finding suitable loci and nodes for therapeutic intervention will always present new opportunities and challenges. Using such bioinformatic nodes and network analyses information, as has been deployed for dry AMD and IRDs [ 99 , 100 ] to unearth novel and repositioning of existing drugs, researchers are sure to make meaningful discoveries for the treatment of OHT/POAG over the next few years. Potential interactions of the several genes discussed above and their relationship to OHT have been presented in a pictorial manner [ 97 ], and novel pathways and components have been discussed [ 25 ].…”