Imibic headquarters./Photo: Europa Press Imibic headquarters./Photo: Europa Press An international team of researchers from France, Switzerland and Spain, in the latter case from the Maimonides Institute for Biomedical Research of Córdoba (Imibic) and the University of Córdoba (UCO), has developed a therapy based on the GnRH protein, which has improved the cognitive functions of a small group of men with Down syndrome. As reported by Imibic in a note, the study, whose results have been published in the prestigious journal ‘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 impaired cognitive ability. 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 capacity -typical of neurodegenerative diseases- and suffer from possible sexual maturation deficits 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”, as explained by the co-author of the study, the Imibic, UCO and Ciber Physiopathology researcher of Obesity and Nutrition, Manuel Tena-Sempere. 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 group of researchers from Lille participating in this study, whose first author is María Manfredi-Lozano, who has a doctorate from the UCO and who completed her predoctoral training at Imibic before beginning her postdoctoral training in France, performed a proof of concept in mice to reset the GnRH system and try to get it to work properly. Using different approaches and tests to review the cognitive and olfactory function of the mice, they demonstrated that activating the GnRH neurons normalized the system and improved both functions. These findings were later 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 and olfactory tests, and MRI examinations, found that the treatment had not improved olfactory function but cognitive function. According to the study, six of the seven patients achieved better three-dimensional representation, better understanding of instructions and reasoning, attention and memory. According to Tena-Sempere, “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.” 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 cut down the times if it is approved for this use », as she has specified. Apart from 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.