Science: A treatment that could improve cognitive function in people with Down syndrome

Down syndrome, also known as trisomy 21, affects one in 800 births and causes a variety of clinical manifestations, including cognitive decline

Dysfunction of GnRH-secreting neurons found in Down syndrome

Recent discoveries suggest that neurons expressing gonadotropin-releasing hormone (GnRH) -- a hormone known for regulating reproduction through the hypothalamus -- may also act on other brain regions, playing in other functions such as cognition potential effect

Based on this idea, a team from the Lille Neuroscience and Cognition Laboratory, led by Vincent Prévot, Research Director at Inserm, investigated the mechanisms that regulate GnRH in a mouse model of Down syndrome

The lab demonstrated that the five microRNA strands found on chromosome 21 that regulate the production of this hormone are dysfunctional

Restore GnRH secretion, restore cognitive function

Inserm scientists then demonstrated that restoring the physiological function of the GnRH system restored cognitive and olfactory function in trisomic mice

These findings in mice were discussed by Nelly Pitteloud, professor in the Faculty of Biology and Medicine at the University of Lausanne and chair of the CHUV Department of Endocrinology, Diabetes and Metabolism

Therefore, the researchers decided to test the efficacy of pulsatile GnRH therapy on cognitive and olfactory deficits in trisomic mice, following the same protocol as in humans

Pulsed GnRH therapy improves cognitive function and neural connectivity in small patient population

The next stage for scientists and doctors is to conduct clinical trials on patients to assess the effects of this treatment

From a clinical standpoint, 6 of the 7 patients showed improved cognitive performance, with better three-dimensional representations, better understanding of instructions, and improved reasoning, attention, and episodic memory

These data suggest that the therapy works on the brain by enhancing communication between certain regions of the cerebral cortex

These promising findings now warrant a larger study -- including women -- to confirm the treatment's efficacy in people with Down syndrome, as well as other neurodegenerative diseases such as Alzheimer's disease 's curative effect

Journal Reference:

1. Maria Manfredi-Lozano, Valerie Leysen, Michela Adamo, Isabel Paiva, Renaud Rovera, Jean-Michel Pignat, Fatima Ezzahra Timzoura, Michael Candlish, Sabiha Eddarkaoui, Samuel A.