Rett Gene Therapy NGN-401 has been cleared to advance into clinical trials

US Food and Drug Administration (FDA) approved NeuroGenExperimental new drug application of NGN-401, an experimental gene therapy for Rett syndrome.

This paves the way for a planned Phase 1/2 clinical trial of the treatment for girls with Rett syndrome, to begin later this year.

“We believe the preclinical profile of NGN-401 is very compelling, with the strongest results to date obtained across multiple animal models,” said Rachel McMinn, PhD, CEO and founder of Neurogene. press release. “Clearance of NGN-401 by the US Food and Drug Administration (FDA) marks a major milestone for Neurogene and the Rett syndrome community and underscores our commitment to transforming devastating neurological diseases into treatable conditions, improving the lives of patients and families affected by these rare diseases.”

Mainly Rett syndrome due to mutations In the MECP2 The gene responsible for the production of the MeCP2 protein, which is involved in the processes that regulate brain development and function. Because MECP2Rett syndrome, located on the X chromosome, occurs almost exclusively in girls. Affected males usually do not survive infancy or have more symptoms because they do not have a healthy second X chromosome. MECP2 Copying genes to compensate for mutations.

NGN-401 provides complete copies of a file MECP2 The gene using a harmless adeno-associated virus as a carrier.

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Rett syndrome is a particularly challenging disorder for gene therapy because of the need to deliver therapeutic levels of gene therapy MECP2without also causing significant side effects associated with many genes [activity]McMain said.

To get around this, NGN-401 uses Neurogene’s proprietary gene regulation technology. MECP2 Copying genes. Unlike conventional gene therapy, where cells can be ‘overdosed’ with too many copies, EXACT, developed in collaboration with the University of Edinburgh, can be tuned to deliver a narrow range of gene expression levels.

Neurogene tested the efficacy, tolerability, and toxicity of NGN-401 in preclinical studies. Enter into the cerebrospinal fluid, which surrounds the brain and spinal cord, resulted Big improvements In survival and disease burden in a Rett syndrome mouse model compared with untreated animals.

The treated animals showed well-regulated levels of MeCP2 in key RET brain regions, in contrast to conventional gene therapy, which yielded variable and very high protein levels. While NGN-401 was considered safe and well tolerated in mice and non-human primates, a similar dose of conventional gene therapy induced severe toxicity in mice and early signs of toxicity in primates.

Neurogene plans a phase 1/2 trial to evaluate the safety, tolerability, and efficacy of NGN-401 in girls with Rett syndrome. The trial will be open-ended and one-arm (without the placebo group), with participants receiving a single dose into the cerebrospinal fluid.

Trial design will include comments from the US Food and Drug Administration Rett Syndrome Research Fundand the Rett Syndrome Foundation International. Neurogene plans to open more than one recruitment center and will start the trial this year.

said Bernard Sutter, MD, assistant professor of pediatrics and neurology at Baylor College of Medicine and a neurologist at Texas Children’s Hospital.

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