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Credit: https://www.genengnews.com/topics/translational-medicine/stem-cells/stem-cell-model-allows-drug-screening-for-age-related-macular-degeneration/

Genetic Profiling of Stem Cell Models Could Yield New Cures

December 13, 2021

  • Using stem cell-derived models, scientists have successfully created an analog for cells affected by age-related macular degeneration. 
  • Scientists genetically analyzed the AMD models to determine their resistance to AMD. 
  • The most and least resistant genotypes were compared to a drug database to determine treatment options for AMD. 
Age-related macular degeneration (AMD) is a condition that results in an irreversible loss of vision. AMD is characterized by pathological protein deposits under the retinal pigment epithelium (RPE), a part of the eye necessary to sustain the eye’s photoreceptor cells. If the RPE is damaged, the light-sensitive photoreceptor cells slowly die over time and no longer communicate light impulses to the optic nerve. With no known treatment, AMD usually progresses from noticeable vision loss to total blindness within years.  New doors have recently been opened into research paths for novel AMD treatments. Scientists have successfully created a model of AMD using stem cells. Researchers were able to program pluripotent stem cells to become retinal pigment epithelium cells. Technicians can create stem-cell-derived RPE cells in a laboratory, and researchers can perform experiments on the lab-grown cells without risk to AMD patients.  Clinical research has established the benefit of stem-cell-derived models; using lab-grown cells. Scientists identified two drugs that inhibited the progression of AMD in the model cells. The toxins simulated rapid aging, and the model cells began demonstrating AMD’s characteristic hallmarks.  The scientists examined the genotype, or genetic makeup, of the cells that experienced the worst AMD-related effects. Analysis of the cell’s genotype indicated several genetic risk factors that, when present in a human, likely increase their risk of being diagnosed with AMD. Armed with this genetic model, the researchers combed through a database of over 1,200 medications. The search algorithm flagged drugs that interacted with the high-risk genetic pathways the researchers identified in the model cell.  Of the hundreds of drugs they searched, only two produced a promising match. One is aminocaproic acid, a protease inhibitor. The other is L745, which reduces complement inflammation by directly interacting with the cell’s dopamine receptors. Of the two drugs, L745 is the most promising. Both of these drugs will likely make their way to the next stages of testing to determine if they are eligible candidates for the treatment of AMD.  Credit: https://www.genengnews.com/topics/translational-medicine/stem-cells/stem-cell-model-allows-drug-screening-for-age-related-macular-degeneration/ 

References: https://www.genengnews.com/topics/translational-medicine/stem-cells/stem-cell-model-allows-drug-screening-for-age-related-macular-degeneration/

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