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A new treatment to improve cognitive function

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Maria Gill
Maria Gill
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People with trisomy 21 — about one in every 800 births — have an extra chromosome. This extra chromosome has a characteristic that would explain one of the clinical manifestations of the disease: cognitive decline. However, this can be improved thanks to a treatment that was successfully tested by scientists from Inserm (Lille) and the global center of the Hospital Vaudois (Lausanne) on a small group of people with trisomy 21.

The researchers proceeded with several steps, described in the review Science. The team from the Lille Laboratory of Neurosciences and Cognition (Inserm/University of Lille/CHU in Lille) first started with a recent discovery related to the neurohormone GnRH, which is involved in the onset of puberty and fertility. It has recently been known that it also plays a role in maintaining cognitive function. So the researchers used mice genetically modified to reproduce human trisomy, in order to study the mechanism of GnRH regulation in this context.

Neurological abnormality

They discovered that five microRNA strands involved in the production of this hormone located on chromosome 21 were edited. In other words, in a mouse model of trisomy 21, an abnormality was observed in GnRH-secreting neurons. This leads to progressive cognitive impairment.

Is it irreversible or is it possible to reverse? This is where the doctors from Vu University Hospital Center come in, who specialize in the treatment of congenital GnRH deficiency, a rare disease that manifests itself in the absence of spontaneous puberty in adolescents. The treatment, which consists of injecting GnRH by reproducing the natural pulsing rhythm of secretion of this hormone, was tested in a mouse model of trisomy 21 to see if it could act on cognitive function.

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With success, the team showed, within just 15 days of a treatment similar to the planned protocol, the mice had restored cognitive functions. And decided to take the next step: to test the effectiveness of the treatment in humans. So a pilot clinical trial was conducted on seven men with trisomy 21, aged 20 to 50 years.

6 out of 7 patients

Both participants received a dose of GnRH every 2 hours subcutaneously for 6 months, using a pump placed on the arm. At the end of the trial, cognition tests showed improved performance in 6 of 7 patients: better 3D representation, better understanding of instructions, and improvement in thinking, attention and episodic memory. Visible changes on MRI.

These results indicate that pulsed GnRH treatment produces effects on the brain, in particular by enhancing communication between specific regions of the cortex, making it possible to improve cognitive function. Therefore, this treatment is promising, and not only for people with trisomy 21: it is possible that some neurodegenerative diseases, including Alzheimer’s, are involved. Provided that the treatment is validated more widely, including in women.

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