GnRH replacement therapy has had amazing benefits for people with Down syndrome

This article is from NEJM Journal Watch

Surprising Benefit from GnRH Replacement in Down Syndrome

Amazing benefits of GnRH replacement therapy for people with Down syndrome

Reviewed by Anthony L.
Komaroff, MD

Pulsed gonadotropin-releasing hormone for 6 months in patients with Down syndrome (DS) improves cognitive function
.

Trisomy 21, or DS, causes progressive cognitive impairment at a young age, as well as premature deposition
of Alzheimer's disease-like brain plaques and tangles.
European researchers have observed that DS patients also have fewer neurons producing gonadotropin-releasing hormone (GnRH) over time, so they wanted to understand whether this was the cause
of cognitive loss.

Using a trisomy 21 mouse model (such as DS patients, which also have low fertility, progressive cognitive decline, and fewer neurons that produce GnRH), the researchers found that GnRH neuronal reduction was associated with altered expression of several microRNAs (miRNAs), including a reduction
in miRNAs known to promote the maturation of GnRH neurons.
Supplementation of this miRNA increases the number of GnRH neurons
.
This intervention, or pulse, was given to GnRH itself, which improved cognitive function
in these mice.

Seven patients with DS (mean age, 26 years; These patients were determined by functional magnetic resonance imaging to have cognitive impairment and brain network connection impairment) received pulsed GnRH therapy for 6 months: 6 patients had improved cognitive function and brain network connectivity
.

comments

The results of this small human study are shocking, and the mouse study suggests that the mechanism seems plausible
.
Progressive loss of GnRH neurons may be one of
the causes of cognitive loss in DS patients.
There seems to be a need for larger controlled trials
of DS and possibly Alzheimer's disease.

Articles that were commented on

Manfredi-Lozano M et al.
GnRH replacement rescues cognition in Down syndrome.
Science 2022 Sep 2; 377:1064.
(https://doi.
org/10.
1126/science.
abq4515)