Estrogen Prevents Oxidative Damage to the Mitochondria in Friedreich's Ataxia Skin Fibroblasts

Estrogen Prevents Oxidative Damage to the Mitochondria in Friedreich's Ataxia Skin Fibroblasts. Richardson TE , Yu AE , Wen Y , Yang S-H , Simpkins JW (2012), PLoS ONE 7(4): e34600. doi:10.1371/journal.pone.0034600.

Abstrac:
Estrogen and estrogen-related compounds have been shown to have very potent cytoprotective properties in a wide range of disease models, including an in vitro model of Friedreich's ataxia (FRDA). This study describes a potential estrogen receptor (ER)-independent mechanism by which estrogens act to protect human FRDA skin fibroblasts from a BSO-induced oxidative insult resulting from inhibition of de novo glutathione (GSH) synthesis. We demonstrate that phenolic estrogens, independent of any known ER, are able to prevent lipid peroxidation and mitochondrial membrane potential (ΔΨm) collapse, maintain ATP at near control levels, increase oxidative phosphorylation and maintain activity of aconitase. Estrogens did not, however, prevent BSO from depleting GSH or induce an increased expression level of GSH. The cytoprotective effects of estrogen appear to be due to a direct overall reduction in oxidative damage to the mitochondria, enabling the FRDA fibroblast mitochondria to generate sufficient ATP for energy requirements and better survive oxidative stress. These data support the hypothesis that phenol ring containing estrogens are possible candidate drugs for the delay and/or prevention of FRDA symptoms.

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Rare diseases and orphan drugs

Rare diseases and orphan drugs, Irena Melnikova, Nature Reviews Drug Discovery 11, 267-268 (April 2012) | doi:10.1038/nrd3654

It is now widely recognized that rare diseases provide attractive niche opportunities for biopharmaceutical companies

Since 1983 when the Orphan Drug Act (ODA) was approved in the United States to promote the development of treatments for rare diseases more than 2,500 small molecules and biologics have been designated as orphan drugs, and currently, for a wide variety of rare diseases there are 460 medicines in clinical trials. The economic incentives for the industry, such as 7 years of market exclusivity, tax credits for certain development costs and application fee waivers helped to get this success, Japan, Australia and the European Union health autorities also worked in the same direction.

Over 80% of rare diseases are genetic in origin, they need a very different aproach, major strategies include: enzyme replacement, gene therapy or manipulation of gene expression.