SRY and male bias in Parkinson’s disease
A drug to stop brain cell death in Parkinson’s disease.
Parkinson’s disease is the second most common neurodegenerative disease with 32 Australians newly diagnosed every day. So there is a critical need to stop the disease from progressing. Current therapies only alleviate symptoms. In several experimental models of PD (human, mouse and rat neuronal cell lines, and toxin-induced rat models) we showed that the SRY is ectopically expressed at abnormally high levels1. Our so-called ‘anti-sense SRY’ gene therapy specifically targeted SRY and reduced levels of protein to near-physiological; in so doing, the drug slowed cell death and consequent movement deficits in rat models2. The SRY gene sequence differs considerably between animal species. The current drug formulation targets the sequence of the rat version of the SRY gene but only 40% of the gene sequence is similar between humans and rats. The project involves the design and optimisation in vitro of a humanised version of our DNA-based drug. Nextgen variant antisense SRY DNA oligos will be synthesised and tested in human neuronal cell lines and SRY levels and transcriptional activity analysed.
Lee J, Pinares-Garcia P, Loke H, Ham S, Vilain E, Harley V (2019) Sex-specific neuroprotection by inhibition of the Y-chromosome gene, SRY, in experimental Parkinson’s disease. PNAS 116(33):16577-16582.
Czech D P , Lee J, Correia J, Loke H, Moller E K, Harley V (2014) Transient neuroprotection by SRY upregulation in dopamine cells following injury in males. Endocrinology 155: 2602-12.