The annual scientific congress on Rett syndrome, organized by the International Rett Syndrome Foundation and held recently in Boston (USA), was the venue for the presentation of the latest results of the drug QTX153 in preclinical models of Rett syndrome. In the presentation, Dr. Sònia Guil, leader of the Regulatory RNA and Chromatin Laboratory at the Josep Carreras Leukaemia Research Institute, based in Badalona, ​​showed how the administration of QTX153 to mice models of the disease reverses a significant portion of the symptoms associated with Rett syndrome, with very low toxicity.

QTX153 is a small molecule synthesized by the Donostia/San Sebastián-based company Quimatryx and co-developed by the Kærtor Foundation, a pioneer in early-stage drug discovery based in Santiago de Compostela. This molecule is a potent inhibitor of the HDAC6 protein, an important regulator of neuronal activity that is overactivated in Rett syndrome because of a mutation in the MECP2 gene, the underlaying cause of the disease.

Rett syndrome is a rare disorder that affects neuronal development and manifests primarily in girls during infancy, between the first and second year of life. It involves a severe regression of the motor and intellectual abilities of those affected, who had not previously displayed any abnormalities, resulting in a devastating impact on families. To date, there is no approved, effective treatment for this genetic disease.

Preclinical trials of the drug QTX153 were conducted at the Josep Carreras Institute under the supervision of Dr. Guil. They used both human neural cells with mutations in the MECP2 gene, introduced using gene editing techniques, and animal models of the disease. In all cases, the administration of QTX153 showed a significant, though not absolute, recovery of the effects associated with Rett syndrome, such as the internal organization and function of neurons, motor control, and the animals' behaviour.

Although HDAC6 protein inhibitors had been previously tested, none had yet reached advanced stages of development for the treatment of Rett Syndrome, mainly due to its difficulty in reaching the brain. However, QTX153 is a compound that efficiently crosses the blood-brain barrier after oral administration. It has demonstrated its safety, even at high doses, with no adverse effects in animal models.

Overall, the excellent preclinical results of QTX153 place it on the starting line for clinical development in the coming years. The next step will be regulatory validation prior to clinical trials, something the innovation structures of strategic partners Quimatryx, the Kærtor Foundation, and the Josep Carreras Institute are already working on. Thanks to the union of diverse talents, the commitment, and the collaborative work of the centres involved, we are one step closer to having the first effective drug against Rett syndrome.