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Discovery of a possible explanation of differences in ALS progression in men in a project selected and financed by the Thierry Latran Foundation: Metabolic factor PGC-1a modifies course of ALS in men (but not in women)

 Why does physicist Stephen Hawking live with ALS for several decades now, while others succumb to the disease within a few years or even only months?

By studying two cohorts of ALS patients from Germany and Sweden, an international team of investigators coordinated by Ulm neurologist Patrick Weydt and funded by the Latran Foundation has identified a possible explanation. When the symptoms start and how they progress is in part determined by variants in the gene coding for the metabolic regulator protein PGC-1a.

The gene variants, termed SNPs*, can modify symptom onset and survival by several years, reports the group in a recent publication in the journal Human Molecular genetics. Surprisingly, this effect only plays out in men and is not detectable in women. But what mechanism mediates this effect. To address this, the Latran-funded researchers turned to the trusted SOD1-transgenic mouse model of ALS. They were able to reproduce a male-specific effect of PGC-1a in the model system. Their results suggest that the nerve and blood-vessel factor VEGF-A is involved. Also PGC-1a interacts with androgen- and estrogen-like receptors. Further research is necessary to fully explore this new lead.

Our results are the first to show that PGC-1a, which had previously been implicated in Huntington’s disease and Parkinson’s disease also play a role in human ALS” say the first authors Dr. Eschbach, Ms. Schwalenstöcker and Dr. Soyal.

The findings could have useful implications for therapy development in ALS. “To date we make no difference between men and women with ALS. Maybe we need to start to think about gender-specific treatment strategies” says lead investigator and Latran-grantee Dr. Patrick Weydt.