AVXS-201 is an investigational gene therapy developed by AveXis (now part of Novartis) for the treatment of Rett syndrome.

According to AveXis, clinical trials testing AVXS-201 will start soon, pending approval by the U.S. Food and Drug Administration.

How AVXS-201 works

Rett syndrome is an X-linked neurodevelopmental disorder that primarily affects female children. It is caused by mutations in the MECP2 gene, which result in the production of defective methyl CpG binding protein 2 (MeCP2) — important for brain development and regulation of other genes.

There are about 200 mutations identified so far in the MECP2 gene. Gene therapy introduces a normal copy of the gene into cells, which can then compensate for the mutated gene and produce a healthy form of the protein.

In gene therapy, certain modified viruses are used to infect the target cells and deliver a healthy copy of a mutated gene. AVXS-201 uses a category of viruses called adeno-associated virus 9 (AAV9) as vectors or carriers for the normal human MECP2 gene. The gene is engineered in such a way that it can optimally encode for MeCP2 protein in sufficient quantities after delivery.

Once injected, the AAV9 vector carrying the normal form of MECP2 attaches itself onto the cell membrane. Then, the outer shell of the virus breaks down, releasing the gene into the cell. Inside the cell, the newly released MECP2 gene is read by the protein-making machinery of the cell, and healthy forms of the MeCP2 protein are made, thereby compensating for the defective mutation.

AVXS-201 in clinical trials

Preclinical studies testing AVXS-201 in mouse models of Rett syndrome have produced positive results. Its administration has led to the longest surviving Rett syndrome mouse with a marked reduction in symptoms. Treatment with AVXS-201 also showed no side effects.

Similar results were seen in non-human primates, with AVXS-201 not affecting the weight, blood parameters, and liver enzymes up to 18 months after injection. A single injection of AVXS-201 was shown to target the whole central nervous system, and there were no indications of tissue damage or disease.

Other information

Although gene therapy is a promising approach, it carries risks of unpredictability, toxicity, inflammation, and even cancer.

However, regulations are in place to protect those who participate in gene therapy clinical trials, and gene therapy efforts continue to get funded extensively with the hope of finding a cure for genetic disorders.

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