QTX153 reverses Rett symptoms and crosses key drug delivery barrier

At the recent International Rett Syndrome Foundation Annual Scientific Congress – new preclinical findings for the drug QTX153 were announced. The results, presented by Dr Sònia Guil of the Josep Carreras Leukaemia Research Institute, highlighted the drug’s potential to reverse key symptoms of the disease in mouse models with minimal toxicity.

Targeting a critical protein in Rett Syndrome

QTX153 is a small molecule developed by the company Quimatryx and co-developed with the Kærtor Foundation – a pioneer in early-stage drug discovery. The molecule acts as a potent inhibitor of HDAC6 – a protein that becomes overactive in people with Rett syndrome due to mutations in the MECP2 gene – the root cause of the disease.

A rare and devastating condition

Rett syndrome is a rare genetic disorder affecting brain development, typically manifesting in girls between the ages of one and two. It leads to severe regression of motor and cognitive functions in previously healthy children – placing an immense emotional and practical burden on families. Currently, no approved treatment effectively addresses the condition.

Preclinical data show functional recovery

Dr Guil’s team conducted preclinical trials using both gene-edited human neural cells and animal models carrying MECP2 mutations. They found that the administration of QTX153 to mice models of the disease reverses a significant amount of the symptoms associated with Rett syndrome, with very low toxicity.

Treated models showed  improvements in neuronal structure,  motor coordination and behaviour – key areas typically impaired in Rett syndrome.

A step ahead in drug delivery

One of the major stumbling blocks in developing Rett syndrome treatments has been delivering drugs to the brain. While other HDAC6 inhibitors have been explored, few have advanced due to their inability to cross the blood-brain barrier. In contrast, QTX153 is designed to overcome this barrier effectively.

QTX153 is a compound that efficiently crosses the blood- brain barrier after oral administration and has demonstrated its safety, even at high doses, with no adverse effects in animal models.

Toward clinical trials

Following promising preclinical results, QTX153 is advancing toward human trials. The next step will be regulatory validation, with  Quimatryx, the Kærtor Foundation and the Josep Carreras Institute actively preparing for clinical development.