A team of international scientists has discovered a new treatment that could help improve cognitive function in patients with Down’s Syndromea condition caused by trisomy of chromosome 21 and which affects one in 800 births.
As the researchers have explained, Down syndrome presents various long-term difficulties such as cognitive decline due to a early Alzheimer-like deteriorationdefects of myelination that slow down the electrical impulses of the neurons, loss of smell and subfertility.
Until now, there has been no viable option to alleviate the cognitive and olfactory deficits of this condition, but the new study published this Thursday in the journal Science ensures that restore gonadotropin-releasing hormone (GnRH)an essential protein in reproductive function, with pulse therapy is the solution.
In humans, impaired GnRH secretion leads to Kallmann syndrome, which manifests with olfactory defects, gonadal immaturity, and infertility. “We therefore wondered if the progressive deficits seen in Down syndrome had any correlation with GnRH maturation,” the article explains.
The therapy increased the performance of six of the seven patients
Specifically, the scientists found that pulsatile GnRH treatment for six months improved both cognitive performance and functional brain connectivity in six of seven patients in a pilot trial. That is, the therapy worked for 85% of men between the ages of 20 and 50 to which, every two hours, a dose of GnRH was administered to simulate its correct secretion.
To get to this point, several tests were carried out with Ts65Dn trisomic mice, the most used in Down syndrome research by replicating regions analogous to human chromosome 21. These animals also present subfertility and progressive cognitive and olfactory alterations similar to those of the patients.
By studying the mice, the researchers observed that the neurological symptoms of the condition progressed in parallel with a postpubertal loss of GnRH neurons and fibers in the hypothalamus, as well as in extrahypothalamic regions. In addition, the adult specimens presented an imbalance in a complex network of microRNAs that functions as a “switch” for GnRH.
“In fact, we observed that the elements of this switch were deregulated from the minipubertal period, long before the appearance of deficits cognitive or olfactory,” the article suggests.
Restoring GnRH in adults is possible
Following the initial findings, the team also discovered that the overexpression of a key microRNA involved in the “switch” that promotes the development of GnRH, the miR-200bsuppressed deficits in neuron activity as well as in olfaction and cognition in trisomic mice.
Likewise, it was found that reinducing microRNA in adulthood, long after the GnRH switch, also increased the number of “GnRH-expressing neurons in the hypothalamus.”
The study has been led by the University of Lille (France) and the University Hospital of Lausanne (Switzerland), but has also had the participation of the University of Córdoba (UCO) and the August Pi i Sunyer Biomedical Research Institute (Idibaps).
According to the researchers, it will “pave” the way for future therapeutic implications that can be very useful.
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