Therapy with a compound used for fertility 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 cognitive functions of a small group of patients with Down syndrome.

The study, whose results are published today in Science, has 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 Institute of August Pi i Sunyer Biomedical Research (Idibaps).

Down syndrome, which affects one in 800 people, is the leading cause of intellectual disability and causes various clinical manifestations, including the deterioration of cognitive capacity. 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 men.

A protein is the one that enhances cognitive deterioration

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

However, at the Neuroscience and Cognition Laboratory in Lille, led by Vincent Prévot, researchers found that in mouse models of Down syndrome this protein does not work 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 review the cognitive and olfactory function of mice, showed that activating GnRH neurons normalized the immune system. and improved both functions.

A study with seven patients

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

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 and olfactory tests and magnetic resonance imaging, found that the treatment had not improved olfactory function but cognitive function.

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

“Promising Results” in Alzheimer’s

“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“, comments Tena-Sempere.

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

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 finds” which can be very useful for clinical research.

We must be careful not to create too many expectations among families

In the opinion of Mara Dierssen, an expert neurobiologist in Down syndrome at the Center for Genomic Regulation, the experiments in 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. So, while certainly interesting and promising, we must be careful not to generate too many expectations between families” and take into account that the study has only been done in men, he points out.