Girl with Down syndrome sitting with her mother
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Results from a study in mice and a small number of men with Down syndrome show gonadotropin-releasing hormone therapy could help improve cognitive function in individuals with the genetic condition.

The authors emphasize that the study is early stage and a larger randomized controlled trial is needed to confirm the findings, but, if validated, the team believes gonadotropin-releasing hormone therapy could help mitigate some of the cognitive issues experienced by individuals with the condition.

Nelly Pitteloud, professor at the Faculty of Biology and Medicine of the University of Lausanne, and colleagues previously investigated links between the reproductive gonadotropin-releasing hormone (GnRH) and Down syndrome.

While the gene for human GnRH (GNRH1) lies on chromosome 8, microRNA that regulate the expression of the hormone are linked with chromosome 21 and this microRNA is dysfunctional in people with Down syndrome. This may explain why people with Down syndrome often have olfactory, reproductive and cognitive defects similar to those with low levels of GnRH.

In this study, which was published in Science, Pitteloud and colleagues first studied a mouse model of Down syndrome in detail and observed that hypothalamic GnRH-expressing neurons did not develop normally and the mice had cognitive, olfactory and reproductive abnormalities.

When a key GnRH regulating microRNA was introduced to the adult mice with these symptoms, GnRH neurons began to function again and symptoms were reduced.

Based on the mouse studies, the team carried out a small pilot study in 7 men with Down syndrome to test the effects of pulsatile treatment (pulsed to mimic natural expression of the hormone) with GnRH hormone. This type of treatment is currently used to treat individuals with GnRH-related conditions such as Kallman syndrome.

In this group, 6 months of the treatment appeared to result in significant improvements in cognitive ability and functional brain connectivity, although no notable effects on olfaction were observed.

“In Down syndrome, pulsatile GnRH therapy is looking promising, especially as it is an existing treatment with no significant side effects,” notes Pitteloud, in a press statement. However, to be confirmed, a randomized control trial in both men and women with the condition is needed, say the authors.

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