FDA approves first drug for Rett syndrome

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FDA approves first drug for Rett syndrome

FDA approves first drug for Rett syndrome.

On March 13, Acadia Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has approved DAYBUE (trofinetide ) for the treatment of Rett syndrome in adults and children two years of age and older .

This also means that DAYBUE has become the first and only drug approved for the treatment of Rett syndrome. The drug is expected to be on the market by the end of April.

FDA approves first drug for Rett syndrome

Acadia CEO Steve Davis said that this approval is an important milestone for Rett syndrome patients and their families and Acadia.

As the first FDA-approved drug to treat Rett syndrome, DAYBUE now has the potential to make a meaningful difference in the lives of patients and their families.

Thank you to all Rett Syndrome patients, caregivers, clinical researchers and Acadia employees who have contributed to making this day possible and look forward to making DAYBUE available to patients as soon as possible.

About Rett Syndrome

Rett syndrome , a rare progressive neurodevelopmental disorder that causes severe intellectual disability, loss of motor capacity, and autism-like symptoms, has no cure.

Rett syndrome is caused by loss-of-function mutations in the MECP2 gene located on the X chromosome , and as a result, usually only girls are affected (male patients usually die shortly after birth) .

Patients with Rett syndrome have a period of normal development until 6-18 months of age, followed by marked developmental regression with loss of learned communication skills and use of the hands.

Symptoms of Rett syndrome may also include the development of hand stereotypes, such as wringing and clapping, and abnormal gait.

The FDA’s approval of DAYBUE is due to the results of its Phase 3 clinical trial, which evaluated the efficacy and safety of DAYBUE and placebo in 187 female patients with Rett syndrome aged 5-20 years.

Treatment with DAYBUE demonstrated statistically significant improvements in both co-primary efficacy endpoints compared to placebo, with the most common side effects being diarrhea (82%) and vomiting (29%) .

DAYBUE (trofinetide ) , a novel synthetic analog of the amino-terminal tripeptide of insulin- like growth factor I (IGF-1) , is designed to treat Rett syndrome by potentially reducing neuroinflammation and supporting synaptic function The core symptoms of the syndrome.

It is thought to stimulate synaptic maturation, overcoming the synaptic and neuronal immaturity that characterizes the pathophysiology of Rett syndrome. In the central nervous system, IGF-1 is produced by two main types of brain cells — neurons and glial cells.

IGF-1 in the brain is critical for normal development and response to injury and disease. DAYBUE has been shown to inhibit the production of inflammatory cytokines, inhibit the hyperactivation of microglia and astrocytes, and increase the amount of available IGF-1 that can bind to the IGF-1 receptor.

Gene Therapy for Rett Syndrome

It is well known that women have two X chromosomes, but one of the X chromosomes is randomly inactivated, and each X chromosome has a copy of the MECP2 gene, while most patients with Rett syndrome have only one MECP2 gene mutation, that is, most There is actually a normal MECP2 gene on the inactivated X chromosome in the neurons of Rett syndrome patients , but the gene is not expressed.

So this is an opportunity for the treatment of Rett syndrome, and reactivating this copy of the gene could be a good therapeutic strategy.

In January 2023, the team of X. Shawn Liu of Columbia University and others published a research paper entitled: Multiplex epigenome editing of MECP2 to rescue Rett syndrome neurons in Science Translational Medicine, a sub-journal of Science .

The research team used dCas9-Tet1 to activate the expression of the originally silent MECP2 gene. At the same time, they also used the dCpf1-CTCF based on the new gene editing tool CRISPR-Cpf1 to introduce CTCF protein into the vicinity of MECP2 , further releasing the effect of X chromosome inactivation on the MECP2 gene.

Thus reactivating the normal copy of MECP2 in Rett syndrome neurons and effectively restoring neuronal function, this epigenetic regulation strategy is expected to be developed as a therapy for Rett syndrome.

FDA approves first drug for Rett syndrome