We make tiny stages of progress in hopes that maybe someone can use our research … until one day there’s a breakthrough.
“I look back and I see how my career was focused on gaining knowledge for knowledge’s sake. And that’s not wrong. That’s what researchers do. We make tiny stages of progress in hopes that maybe someone can use our research to make more progress and so on and so on, until one day there’s a breakthrough,” recalls Dr. Isom.
Nowhere has Dr. Isom’s dedication to medicine and research been stronger than in her passionate pursuit of helping children. Over the last 26 years Dr. Isom has led a team of researchers who have worked diligently to solve the puzzle behind Dravet syndrome, a deadly type of pediatric seizure disorder that carries a high risk of Sudden Unexpected Death in Epilepsy (SUDEP).
She was inspired to work toward a cure for SUDEP after meeting families who have lost children to it, or who live in fear that they might. “In patients who have thousands of seizures in their lives,” Dr. Isom says, “we need to understand why they experience the one that kills.”
When epilepsy is caused by gene mutations, drugs often do not stop seizure activity. Therefore, Dr. Isom and her team determined that they needed to get to the source of the problem – the genes themselves. So, they channeled their collective focus into studying the genetic mechanisms that could be altered to stop the seizures at the cellular level.
After years of encouraging findings based on ongoing studies conducted by Dr. Isom’s team and her collaborators, researchers at Stoke Therapeutics heard Dr. Isom present her work to the American Epilepsy Society. They were so impressed with the presentation that they then invited her and her lab to apply their ongoing research to a therapeutic model that Stoke had developed for helping patients with Dravet Syndrome.
In a truly collaborative atmosphere that brought together the leading minds from medicine and science, the teams conducted a study on a mouse model of Dravet syndrome, since mice closely mimic the genetic makeup of humans. What happened next was not only groundbreaking, but virtually unheard of.
Says Dr. Isom, “Together, we prevented seizures and SUDEP in 97 percent of the mice that we tested for 90 days after the initial dose. This means we had a model for long-lasting prevention which, with other toxicology studies, was enough for the FDA to approve a clinical trial in humans. It’s the greatest thing we’ve ever done.”
Because of the breakthrough results, Michigan Medicine was selected as one of the sites for the testing trials that began in August of 2020.
As for the future of ending epilepsy at large, Dr. Isom will continue to head Michigan Medicine’s Isom Lab where she oversees a staff of 17 – and along with her long-time research collaborator, Jack Parent, M.D. in Michigan Medicine’s department of neurology – will remain united in the primary goal of ending SUDEP.
If we can help one child, then it’s worth it.
“Most patients with Dravet syndrome have only 50 percent expression of an essential gene in the brain, and this reduction causes a severe epileptic disease with a high risk of sudden death,” Dr. Isom says. “Our goal is to increase the gene’s expression back to 100 percent and we may have found a way to do that.”
She hopes that the clinical trial could have even wider implications for treating other genetic causes of generalized epilepsy, especially for the large percentage of patients whose epilepsy is not controlled with traditional drugs.
“We come to the lab every day knowing kids are waiting on us. That’s our challenge and our goal. To give them an answer. If we can help one child, then it’s worth it.”
Do you have a remarkable patient story? A moment of breakthrough or discovery? We’d love to hear about it!