Imibic and UCO develop a therapy that improves cognitive function in patients with Down

A international team of researchers from France, Switzerland and Spain, in the latter case from the Maimonides Institute for Biomedical Research in Córdoba (imibic) and the University of Córdoba (UCO), has developed a GnRH protein-based therapywhat has improved cognitive functions of a small group of men with Down’s Syndrome.

As reported by Imibic in a note, the study, whose results have been published this Friday in the prestigious magazine ‘Science’has been led by the University of Lille (France) and the University Hospital of Lausanne (Switzerland), and has had the participation of Imibic and the UCO, as well as the August Pi i Sunyer Biomedical Research Institute (Idibaps), in Barcelona.

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 percent of people with Alzheimer’s experience symptoms similar to those of Alzheimer’s disease.

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

The gonadotropin releasing hormone (GnRH) is an essential protein in reproductive function, “the signal with which the brain controls the reproductive system”, as explained by the co-author of the study, the Imibic, UCO and Ciber Physiopathology of Obesity and Nutrition researcher , Manuel Tena-Sempere.

However, at the Neuroscience and Cognition laboratory in Lille, Directed by Vincent Prevotthe 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 group of researchers from Lille participating in this study, whose first author is Maria Manfredi-Lozano, who is doctor from the UCO and who did his predoctoral training at Imibic before starting his postdoctoral training in France, carried out a proof of concept in mice to restore the GnRH system and try to make it work properly.

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

These findings were tested later in a clinical phase which was 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 every two hours he gave them a dose of GnRH for simulate the secretion of this hormone at normal levels and achieve a physiological pattern, like the one that people without this syndrome have.

After six months of treatmentthe 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.

According to Tena-Sempere, “the work points to the possible utility of the compound to treat cognitive problems derivatives of Down syndrome, but has also shown promising results in mouse models of Alzheimer’s.

Although larger clinical studies that also 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 this will help shorten the time if it is approved for this use”, as 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”which can be very useful for clinical research.


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