They test a new therapy to improve cognitive functions in patients with Down syndrome – ConSalud

In a study published in the journal ‘Science’, they have tested the efficacy of GnRH injection therapy in improving cognitive functions in a small group of Down syndrome patients. The team from the National Institute for Research in Health and Medicine of France (Inserm) together with their counterparts from the University Hospital of Lausanne (CHUV), in Switzerland, revealed a dysfunction of GnRH neurons in an animal model of GnRH syndrome. of Down and its repercussions in the deterioration of cognitive function associated with the disease. A pilot study was then conducted to test GnRH pulsatile injection therapy in seven patients. The results were promising as the therapy improved cognitive function and brain connectivity. Down syndrome, also known as trisomy 21, affects one in 800 births and causes various clinical manifestations, including impaired cognitive ability. With age, 77% of people with Alzheimer’s experience symptoms similar to those of Alzheimer’s disease. The gradual loss of olfactory capacity, typical of neurodegenerative diseases, is also frequent from the prepubertal period, with possible deficits in sexual maturation in men. The laboratory showed that five microRNA chains that regulate the production of this hormone – found on chromosome 21 – are dysfunctional Recent discoveries have suggested that neurons that express gonadotropin-releasing hormone (GnRH) – known to regulate reproduction at through the hypothalamus – could also act in other regions of the brain with a potential role in other functions, such as cognition. With this idea in mind, the team from the Neuroscience and Cognition Laboratory of Lille (Inserm/University of Lille, University Hospital of Lille), led by Inserm’s research director, Vincent Prévot, studied the mechanism that regulates GnRH in models Down syndrome mouse. The laboratory showed that five microRNA chains that regulate the production of this hormone – found on chromosome 21 – are dysfunctional. This supernumerary chromosome then causes abnormalities in neurons that secrete GnRH. These results were confirmed both at the genetic and cellular level. The Inserm scientists were able to show that the progressive cognitive and olfactory impairments observed in mice were closely related to dysfunctional GnRH secretion. Restoring the physiological function of the GnRH system restores cognitive and olfactory functions in trisomic mice Inserm scientists were able to demonstrate that restoring the physiological function of the GnRH system restores cognitive and olfactory functions in trisomic mice. These findings in mice were discussed with Nelly Pitteloud, professor at the Faculty of Biology and Medicine at the University of Lausanne and head of the CHUV Department of Endocrinology, Diabetology and Metabolism. Her research focuses on congenital GnRH deficiency, a rare disease manifested by the absence of spontaneous puberty. These patients are given pulsatile GnRH therapy to reproduce the natural rhythm of GnRH secretion, in order to induce puberty. Therefore, the researchers decided to test the efficacy of pulsatile GnRH therapy on cognitive and olfactory deficits in trisomic mice, following a protocol identical to that used in humans. After 15 days, the team was able to demonstrate the restoration of the olfactory and cognitive functions of the mice. The next stage for scientists and doctors was a pilot clinical trial in patients to test the effects of this treatment. Seven men with Down syndrome, ages 20 to 50, received a subcutaneous dose of GnRH every two hours for 6 months through a pump placed in their arm. Cognitive and olfactory tests as well as MRI examinations were performed before and after treatment. Cognitive performance increased in 6 of 7 patients with better three-dimensional representation, better understanding of instructions, improved reasoning, attention, and episodic memory Clinically, cognitive performance increased in 6 of 7 patients with a better three-dimensional representation, a better understanding of instructions, an improvement in reasoning, attention and episodic memory. However, the treatment had no impact on olfactory ability. These measures of improved cognitive functions were confirmed by brain imaging performed by the CHUV Department of Clinical Neurosciences, which revealed a significant increase in functional connectivity. These data suggest that the treatment acts on the brain by reinforcing communication between certain regions of the cortex. “The maintenance of the GnRH system seems to play a key role in the maturation of the brain and cognitive functions,” explains Prévot. “In Down syndrome, pulsatile GnRH therapy shows promise, especially since it is an existing treatment with no significant side effects,” adds Pitteloud. These promising results now justify the launch of a larger study, including women, to confirm the efficacy of this treatment in people with Down syndrome, but also for other neurodegenerative conditions such as Alzheimer’s disease. Because we all need health. ..