The most common cause of Dravet syndrome is a genetic mutation in the SCN1A gene that results in a reduction in a type of sodium channel (Nav1.1) in the brain. A new type of medicine, STK-001, designed by Stoke Therapeutics increases healthy copies of the Nav1.1 sodium channel in pre-clinical animal and cell models. Stoke Therapeutics is now enrolling for the MONARCH study to assess if this works as a treatment for patients with Dravet syndrome.
STK-001 is an anti-sense oligonucleotide (ASO). ASOs are small molecules that target RNA, and several ASOs are currently being explored to treat different human diseases. STK-001 does not make any changes to the DNA, so it is not considered “gene therapy.” RNA is the middle step between genes on your DNA (like SCN1A) and the production of proteins that do the work (like the Nav1.1 sodium channel). Individuals with mutations in the SCN1A gene often make fewer functional copies of the Nav1.1 sodium channel. STK-001 specifically targets the cells in the brain that already express the SCN1A gene, mainly neurons, and increases the number of healthy Nav1.1 sodium channels that are made from the RNA.
STK-001 significantly decreased seizure frequency and increased survival in a mouse model of Dravet syndrome. STK-001 has also been tested in healthy non-human primates and shown to increase the Nav1.1 sodium channel without any adverse effects on the animals. These pre-clinical results are encouraging, but it is yet to be seen how this will work in human patients with Dravet syndrome.
The MONARCH study is a Phase 1/2a clinical trial focusing on safety and tolerability of STK-001 in patients with Dravet syndrome. They will also assess how STK-001 affects seizures and other health measures. The study will include a 1- to 2-month baseline observation period, a single injection of STK-001 by lumbar puncture (spinal tap), and a 6-month observation period. Patients and caregivers will need to travel to study sites about 8 times and complete 3 phone calls. After completion of the study, patients may be eligible to enter another study with additional doses of STK-001. While much is still unknown, it’s thought that most patients will need 2-3 doses per year.
You can find more details in this report by Nicole Villas: Stoke Community FAQ April 2020