Rare Disease Day is recognized on the last day of February each year. The main objective of the initiative is to raise awareness amongst the general public and decision-makers for the 300 million people affected by rare diseases globally and the impact these diseases have on patients’ lives. In the US, the Orphan Drug Act of 1983 defines a disease as rare when the condition affects fewer than 200,000 people. Other countries have their own official definitions. For example, the European Union defines a rare disease as one that affects fewer than 1 in 2,000.
Those living with rare diseases often experience significant delays in diagnosis and access to treatment options. Treatments are scarce due to the uncommonness of the diseases and little interest from drug companies. Fortunately, the Orphan Drug Act of 1983 created financial incentives to develop new drugs for rare diseases and, as a result, research has increased. However, there are still more than 7,000 different rare diseases that exist today, of which only 5% have treatments.
In advance and support of Rare Disease Day, we will be featuring five different rare diseases over the next five days to bring awareness to these uncommon, yet impactful illnesses.
Rett Syndrome is a rare non-inherited genetic neurological disorder that occurs almost exclusively in girls and leads to severe impairments, affecting nearly every aspect of the child’s life: the ability to speak, walk, eat, and even breathe easily. Rett syndrome is usually recognized in children between 6 to 18 months as they begin to miss developmental milestones or lose abilities they had gained. Occurring worldwide in 1 of every 10,000 female births, Rett Syndrome is even rarer in boys. Rett Syndrome can present with a wide range of disability ranging from mild to severe. The hallmark of Rett Syndrome is near constant repetitive hand movement. The course and severity of the disease is determined by the location, type and severity of the mutation and X-inactivation.
There is currently no cure for Rett Syndrome. However, there are a variety of clinical trials in development, including 5 active and 2 upcoming. Recently, the Rett community was looking forward to the start of the AveXis study for the use of Zolgensma® (onasemnogene abeparvovec-xioi) to correct the MeCP2 gene in Rett patients. This is a gene therapy currently on the market for patients under the age of two with spinal muscular atrophy (SMA). The MeCP2 gene provides instructions for making the MeCP2 protein which helps regulate gene activity (expression) by modifying chromatin, the complex of DNA and protein that packages DNA into chromosomes. Mutations affecting the MeCP2 protein are shown to be the almost exclusive cause of Rett Syndrome.
The start of the trial had been delayed, and in August of 2019, the Rett community learned the disappointing news that the FDA denied the submission due to data integrity concerns. AveXis decided to also review data quality and compliance with the preclinical work performed for AVXS-201 and to repeat and add additional pivotal preclinical studies as well as new quality controls. Once these studies are completed, AveXis plans to submit the revised IND (investigational new drug application) to the FDA with the goal of rapidly progressing to clinical trials in Rett Syndrome patients. It is expected that conducting these additional studies and completing the IND will take until the middle of 2020.
Though hope is on the horizon for this rare neurological disorder, it is imperative to continue to raise awareness of Rett Syndrome in order to support aggressive funding for the most promising research for all living with Rett Syndrome and their families.
To learn more about Rett Syndrome, take a look at the list of resources below.