Aging-US: PU-91 drug rescues human age-related macular degeneration cells
09-08-2021Aging-US published a Special Collection on Eye Disease which included "PU-91 drug rescues human age-related macular degeneration RPE cells; implications for AMD therapeutics" which reported that the PU-91 drug upregulates PGC-1α which is a critical regulator of mitochondrial biogenesis.
Since mitochondrial dysfunction is implicated in the pathogenesis of AMD, this study is based on the premise that repurposing of PU 91 might rescue AMD RPE cells from AMD mitochondria-induced damage. The authors report significant improvement in cell survival, mitochondrial health, and antioxidant potential following treatment with PU 91.
Dr. M. Cristina Kenney from The University of California Irvine said, "The incidence of Age-related Macular Degeneration (AMD) is increasing at an alarming rate in elderly population in the United States."
Figure 9. Effect of PU-91 + EI-78 on gene expression. qRT-PCR analysis showed differential expression of PGC-1α (A), Caspase-3 (B), IL-18 (C), VEGF (D), and SOD2 (E) genes in AMD RPE cells at the 72 h time point. Data (n=3) are presented as mean ± SEM and normalized to untreated (UN) AMD cybrids which were assigned a value of 1. Mann-Whitney test was used to measure statistical differences; *p≤0.05. P = PU-91; EI = Esterase Inhibitor.
The incidence of Age-related Macular Degeneration (AMD) is increasing at an alarming rate in elderly population in the United States. Most AMD cases occur among Caucasian Americans, followed by Hispanic and other populations. Despite intensive study, a limited number of FDA-approved treatment options are available for treatment of AMD.
National Eye Institute projection, the estimated number of AMD patients is expected to rise to 5.44 million by 2050. PU-91 is a pro-drug that when metabolized is PPARα ligand and which was developed for the treatment of dyslipidemia.
The drug is estimated to have seen >5 million-years of patient exposure and remains an effective agent for certain dyslipidemias. These findings demonstrated that PU-91 preserved AMD mitochondrial function and integrity, and protected AMD RPE cybrids against oxidative stress-induced and mtDNA-induced apoptotic cell death.
These findings demonstrated that PU-91 preserved AMD mitochondrial function and integrity, and protected AMD RPE cybrids against oxidative stress-induced and mtDNA-induced apoptotic cell death.
The Kenney Research Team concluded in their Aging-US Research Output, "PU-91 rescues AMD RPE cybrids, and potentially could be repurposed as an FDA-approved drug to prevent/treat AMD. Since it improves mitochondrial function and has already been FDA-approved, the candidate therapeutic PU-91 will be an excellent treatmentoption for AMD. Repositioning of PU-91 will be a smoother transition from lab bench to clinic since the pharmacological profiles of PU-91 have been examined already. Furthermore, because of its extensive safety record it could be potentially prosecuted through NDA more rapidly than a drug-like new chemical entity. Bringing a disease modifying therapeutic to market for the most prevalent form of blindness, AMD, has substantial potential benefit for our aging populations world-wide."
Full Text - https://www.aging-us.com/article/102179/text
Correspondence to: M. Cristina Kenney email: mkenney@uci.edu
Keywords: age-related macular degeneration (AMD), RPE, PGC-1α, RPE, mitochondria, FDA-approved drugs
About Aging-US:
Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer’s diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases.
Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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