A unique hormone therapy may help patients with Down syndrome who have mental difficulties, In the pilot study, pulsed gonadotropin-releasing hormone (GnRH) therapy improved cognitive function in seven male Down’s syndrome patients. The team reported in Science that research using mice verified the impact of the method. If this is further proven with more research, the method would be a potential treatment for those who are afflicted.
An error in the division of embryonic cells causes Down syndrome. There are not only two, but three copies of chromosome 21. Trisomy-21 is a genetic disorder that affects one in 800 children and has an impact on both their physical and mental development. Problems with planning, memory, concentration and abstract thinking are frequent, and many afflicted people also have rapid mental deterioration.
The most frequent genetic cause of mental impairment is trisomy-21. However, the available treatments for it are few and of questionable effectiveness.
Function of the Gonadotropin-Releasing Hormone
But things could be changing now. Manfredi-Lozano and his colleagues have discovered a method to address cognitive deficiencies as well as their potential causes. The discovery that patients with Down syndrome often have olfactory abnormalities that develop after puberty and infertility, served as the catalyst for this study. Both have a strong connection to the action of a particular hormone called gonadotropin-releasing hormone (GnRH).
Specialized brain cells in the hypothalamus release GnRH, which largely controls the generation of sex hormones. Recent research, however, indicates that this hormone also influences a number of brain activities and could have an impact on greater mental performance. Manfredi-Lozano and his coworkers stepped in to help with this. They speculate that GnRH may also be involved in some of the mental and physical symptoms of Down syndrome.
GnRH Also Affects How the Brain Works
The researchers initially looked at the brains of mice with Down syndrome. They discovered that these animals had altered GnRH-producing neurons’ activity. Along with the neurons in the hypothalamus, this also had an impact on the hormone-producing brain cells in the cerebral cortex and the hippocampus, two regions associated with cognition and memory.
Additional investigation revealed that these neurons’ abnormalities and the hormones they produced had an impact on the mice’s cognitive as well as physical development. The afflicted mice exhibited the same cognitive impairments and olfactory disorders as the trisomy mice when the expression of the GnRH gene was artificially suppressed in test animals.
The research reveals an unanticipated function for GnRH in cognitive and olfactory functions. The expression of GnRH and its receptor in regions of the brain other than the hypothalamus is directly related to these effects.
The Pulsed Hormones Help Mice with Cognitive Impairments
However, this implies that if the dysfunctional neuronal hormone production could be corrected, it would also be possible to partially treat the mental deficiencies associated with Down syndrome. They achieved this by placing a pump under the mice’s skin that, like the brain cells that produce GnRH, released the hormone in regular bursts. The rats’ learning and memory deficiencies significantly improved after 15 days, according to the researchers.
Will this also help humans with Down’s syndrome, though? GnRH pulse therapy has been licensed for use in humans for some time and is used to treat infertility brought on by GnRH insufficiency. This gave the scientists the chance to perform a pilot study with seven Down syndrome-affected male participants. Four of the seven Down’s patients also had trouble comprehending speech, and all seven had major cognitive abnormalities and olfactory issues.
All seven patients in the pilot study had a tiny pump placed under their skin that delivered dosages of the hormone GnRH every two hours. The seven patients’ mental abilities were once again evaluated by the researchers using standardized tests six months later.
Results
As a consequence, six out of the seven individuals’ cognitive abilities had increased. This was noticeable in executive functions, attention, executive visual-spatial tasks, and episodic memory. Higher-order cognitive processes such as goal-oriented action planning, decision-making, and self-control are included in executive functions. Pulsed hormone treatment also increased linguistic understanding.
This beneficial effect of hormone therapy is also seen in studies of brain function that employ functional magnetic resonance imaging. Following GnRH treatment, the seven subjects had increased connectivity in some brain regions crucial for thinking and memory, including the cortex and hippocampus.
Therapy Has A Lot of Promise
According to the study, these findings point to the potential advantage of such pulsed hormone treatment for persons with Down syndrome, at least for men and women beyond menopause. Such medication may affect the menstrual cycle’s control in women of reproductive age, making them infertile. Therefore, it would be crucial to examine the effects of GnRH medication on female patients. The findings provide enough justification to launch multicenter research on the method.
This surprising finding that GnRH has a cognitive enhancer effect has a lot of promise. A novel approach to treating Down syndrome patients’ cognitive impairments may involve pulsatile GnRH therapy.
