Hormone therapy improves cognitive function in patients with Down syndrome

An international team of researchers has developed a therapy based on the GnRH protein that has improved the cognitive functions of a small group of patients with Down syndrome. The study, whose results are published today in Sciencehas been led by the University of Lille (France) and the University Hospital of Lausanne (Switzerland), and has had the participation of the University of Córdoba (UCO) and the August Pi i Sunyer Biomedical Research Institute (Idibaps).

Down syndrome, which affects one in 800 people, is the leading cause of intellectual disability and causes various clinical manifestations, including impaired cognitive ability. With age, 77% of sufferers experience symptoms similar to those of Alzheimer’s disease.

In addition, people with this syndrome suffer from the gradual loss of olfactory capacity —typical of neurodegenerative diseases— and possible deficits in sexual maturation in the case of males.

Gonadotropin-releasing hormone (GnRH) is an essential protein in reproductive function, “the signal with which the brain controls the reproductive system,” the co-author of the study, Manuel Tena-Sempere, a UCO researcher, explained to EFE. and the Center for Biomedical Research Network (Ciber) of Physiopathology of Obesity and Nutrition.

However, at the Neuroscience and Cognition Laboratory in Lille, led by Vincent Prévot, researchers discovered that in mouse models of Down syndrome this protein does not function properly, which contributes to the cognitive impairment associated with this syndrome. That is, GnRH also plays an essential role in cognitive function.

Based on this finding, the Lille researchers (whose first author is María Manfredi-Lozano, currently at the University of Seville) carried out a proof of concept in mice to restore the GnRH system and try to make it work correctly.

Using different approaches and tests to check the cognitive and olfactory function of the mice, they showed that activating the GnRH neurons normalized the system and improved both functions.

These findings were then tested in a clinical phase carried out at the University Hospital of Lausanne, in a study with seven male patients with Down syndrome aged between 20 and 50 years.

These patients were administered pulsatile GnRH therapy that supplied them with a dose of GnRH every two hours to simulate the secretion of this hormone at normal levels and achieve a physiological pattern, like that of people without this syndrome.

After six months of treatment, the researchers evaluated the effects of the therapy and, using cognitive, olfactory and MRI tests, found that the treatment had not improved olfactory function, but cognitive function.

better understanding

According to the study, six of the seven patients achieved better three-dimensional representation, better understanding of instructions and reasoning, attention and memory.

“The work points to the possible usefulness of the compound to treat cognitive problems derived from Down syndrome, but it has also given promising results in mouse models of Alzheimer’s”, commented Tena-Sempere.

And although larger clinical studies that include women with Down syndrome will be needed, this compound “is already used in fertility treatments, that is, it is not new, but it is known to be safe and its effects are known, all of that It will help cut times if it is approved for this use”, he specified.

Regardless of the therapeutic implications that this study may have in the future, for Tena-Sempere the work is important to remember that basic science can lead to “unexpected findings” that can be very useful for clinical research.

In the opinion of Mara Dierssen, an expert neurobiologist in Down syndrome at the Center for Genomic Regulation, the experiments on mice that have been carried out in this study “are elegant and support the authors’ hypotheses”, she explained to Science Media Center Spain.

“Possibly the weakest part is the clinical study, in which the authors only evaluated seven people with Down syndrome. Therefore, although it is certainly interesting and promising, we must be careful not to generate too many expectations among families” and keep in mind that the study has only been done in men, he pointed out.


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