Socialpost

Complete News World

Junge mit Down-Syndrom

Down syndrome hormonal therapy? – wissenschaft.de

GnRH therapy can reduce cognitive impairments in people with Down syndrome. In a mouse model, researchers discovered that some of the symptoms of Down syndrome may be caused by an abnormal release of this hormone. An already established treatment for people with GnRH deficiency improved cognitive functions both in a rat model and in a pilot study with seven patients with Down syndrome. Larger clinical studies are now being conducted to further evaluate the benefit.

Down syndrome, also known as trisomy 21, occurs in about 1 in every 800 live births, making it the most common genetic cause of intellectual disability. The reason is the presence of an extra chromosome 21. In addition to various physical symptoms, those with it usually have significantly reduced cognitive abilities. In addition, many develop Alzheimer’s-like symptoms in adulthood. Another symptom is the gradual loss of smell, which often begins in pre-puberty. While many women with Down syndrome can have children, most affected men are infertile.

Trisomy 21 disrupts hormone production

A team led by Maria Manfredi Lozano of the University of Lille in France is now searching for a possible treatment for some symptoms of Down syndrome. The authors explain: “Loss of smell, in addition to infertility, is also a typical symptom of patients with congenital gonadotropin-releasing hormone (GnRH) deficiency, the so-called Kallmann syndrome.” GnRH is released by specialized neurons in the hypothalamus and is primarily responsible for stimulating the production of certain reproductive hormones. However, new studies also suggest that it can have an effect on higher brain functions.

See also  Psychology: Are people right with their first impressions? - Knowledge

The similarities in symptoms of Kallmann syndrome and Down syndrome have prompted researchers to look more closely at the role of GnRH in Down syndrome. To do this, they first worked with a mouse model that mimics the changes caused by trisomy 21. In fact, they came across a mechanism that explains why GnRH is a problem in people with Down syndrome: hormone production is regulated by so-called microRNAs. At least five of these microparticles are encoded by regions on human chromosome 21 – and thus are disrupted in people who have three copies of this chromosome.

Promising results in mice

In mice with Down syndrome, Manfredi Lozano and her team demonstrated that it is GnRH deficiency that contributes to cognitive impairment, loss of smell, and impaired sexual maturation in the animals. If the researchers gave the mice GnRH regularly or transplanted the cells that properly produced the hormone, the symptoms eased. After just 15 days of treatment, the mice showed an improvement in cognitive function and also regained their sense of smell. However, the animals were not able to reproduce as a result of the treatment.

“Because of the compelling results in mice, we conducted a pilot study in human Down syndrome patients as a next step,” the researchers wrote. They used a form of therapy already established to treat Kallmann syndrome: A small pump is implanted under the skin on their arm, which administers a small dose of GnRH every two hours. This so-called pulsed GnRH therapy mimics the body’s natural release of the hormone.

Larger clinical trials are needed

Seven men with Down syndrome between the ages of 20 and 50 received this treatment for six months. Before and after, the researchers tested their cognitive abilities and sense of smell and also performed MRI scans. The result: After six months of treatment, six out of seven patients were able to understand instructions better, solve logical tasks better, and had more attention and improved episodic memory. MRI scans also showed increased functional connectivity in the brain. In contrast to mice, the treatment had no effect on the patients’ sense of smell.

See also  Origin of schizophrenia in the brain - gene mutation alters 'gatekeeper' and increases risk of schizophrenia by 40-fold

“Pulsed administration of GnRH appears to be a promising approach, with few expected side effects, to improve cognitive function in a wide range of cognitive decline disorders characterized by impaired GnRH neuronal function,” wrote Han Hoffman of Michigan State University in an accompanying comment. The study also published in the journal Science. “To fully determine the value of pulsatile GnRH in improving cognitive function, a randomized controlled trial involving both sexes is needed.” Women were not included in the pilot study because GnRH can disrupt the menstrual cycle. “However, in women who are past childbearing age or do not wish to become pregnant, pulsed GnRH therapy is likely to be as beneficial as men for improving cognitive performance,” Hoffman said.

Source: Maria Manfredi-Lozano (Université de Lille, France) et al., Science, doi: 10.1126/science. abq4515