Investigational New Therapy Prevents Onset of Dravet Syndrome Symptoms in Mice

Development is first step to helping children with the rare epilepsy syndrome.

2:00 PM

Author | Kelly Malcom

drawing of a pink brain on a dark pink background
Image by Stephanie King.

In a development that may finally offer hope to children with Dravet syndrome and their parents, a new promising investigational therapy appears to alter the destructive course of the deadly disease. 

Lori Isom, Ph.D., chair of the University of Michigan's department of pharmacology and professor of molecular & integrative physiology and neurology and her team have spent several years tracing the developmental pathway of Dravet syndrome, a debilitating genetic disease that causes intractable seizures and can lead to sudden death. Dravet syndrome variants lead to a decrease in the level of a crucial protein that normal brain cells use to control the flow of sodium ions into cells. Neurons use these sodium channels to transmit signals back and forth.

Patients with Dravet syndrome have variants in a sodium channel gene, SCN1A, that in general result in there being only half the amount of the corresponding functional protein, Nav1.1, expressed in the brain. "With only 50% SCN1A expression in the brain, you have a severe epileptic disease with a high risk of sudden death," Isom says.

The team's goal was to increase the gene's expression back up to 100% in neurons using an antisense oligonucleotide that was developed by Stoke Therapeutics, a biotechnology company. In collaboration with Stoke, Isom and her team tested the ASO called STK-001 in a Dravet syndrome mouse model.  

"The brain normally uses sections of genes called poison exons to dial up or down the expression of a particular gene, as an internal regulatory mechanism," explains Isom. "We are taking advantage of a poison exon in SCN1A to increase its expression." Unlike using CRISPR, viruses, or other forms of gene editing, ASOs are reversible. "The problem with gene therapy is you are changing something forever, which is risky especially with the brain. If you make a mistake, there's no going back." 

Injecting the ASO into the brains of mice that carry only one healthy copy of the SCN1A gene two days after they were born led to a 97% survival rate out to 90 days, while just 23% of the untreated mice survived during the same time range. 

"Our thought is that early intervention with an ASO in mice may be able to change brain excitability," says Isom, "And if that's also true for kids with Dravet, that would be incredible." The results are published in the journal Science Translational Medicine. 

Based on the encouraging findings of the mouse study, Stoke recently launched a clinical study to begin evaluating STK-001 in children and adolescents with Dravet syndrome. 

Isom notes that the mouse study could have even wider implications for treating the genetic cause of generalized epilepsy, especially for the third of patients whose epilepsy is not controlled with traditional drugs. "We just need to start over and think about epilepsy in a new light—to get at the genetic source, rather than being reactive and trying to treat something that has already happened."

Paper cited: "Antisense Oligonucleotides Increase Scn1a Expression and Reduce Seizures and SUDEP Incidence in a Mouse Model of Dravet Syndrome," Science Translational Medicine. DOI: 10.1126/scitranslmed.aaz6100

More Articles About: Lab Report Basic Science and Laboratory Research All Research Topics epilepsy Genetic Disorders
Health Lab word mark overlaying blue cells
Health Lab

Explore a variety of health care news & stories by visiting the Health Lab home page for more articles.

Media Contact Public Relations

Department of Communication at Michigan Medicine

[email protected]


Stay Informed

Want top health & research news weekly? Sign up for Health Lab’s newsletters today!

Featured News & Stories 2020 SCN8A Malcolm
Health Lab
New Therapy Stops Seizures in Mouse Model of Rare Childhood Epilepsy
Researchers have made a genetic breakthrough in mice that could lead to new, revolutionary treatment options for SCN8A-related encephalopathy seizure disorder in babies.
person holding arm with band aid teal shirt
Health Lab
More hospitals than ever require staff to get flu shots
Flu vaccination mandates for hospital staff have increased in recent years, especially at hospitals serving veterans
woman laying on floating cell maroon
Health Lab
Circadian rhythm drives the release of important immune cells
A study shows circadian rhythm drives the release of important immune cells in the body.
green background connecting to teal skull with brain inside both just outlines made out of felt
Health Lab
Can preventing inflammation improve heart and brain health?
Michigan Medicine research study aims to address inflammation’s role in diseases of the heart and brain.
Lab of Erin M. Janssen, M.D., Ph.D.
Medical School News
Labs go platinum: Research teams record efforts to achieve sustainability certification
Many Michigan Medicine labs are taking time to ensure that they are doing their part to support the Medical School’s major initiatives, including the push for carbon neutrality.
graphic drawn mouse snoozing in purple background and pink maze around it breathing while sleeping and see pink brain inside head with white sparkles fading in and out
Health Lab
Studies uncover the critical role of sleep in the formation of memories
Two new studies from University of Michigan reveal what's happening inside the brain during sleep and sleep deprivation to help or harm the formation of memories.