Partnership Opportunities

Epilepsy-Focused Medical Devices

Using advanced models to develop and test medical interventions for treatment-resistant epilepsy

Technology Overview

Dravet syndrome is a severe, life-threatening form of epilepsy that starts in infancy and presents with an array of co-morbidities besides seizures. These include sleep disorders, ataxia, cognitive dysfunction, and in some cases, sudden unexpected death in epilepsy (SUDEP). Leigh syndrome results from mutations in nuclear or mitochondrial genes and its symptoms include seizures. Seizures related to these two syndromes are resistant to current therapies.

Dr. Franck Kalume uses advanced in vitro and in vivo models to study the pathways of pediatric epilepsy to identify targets for new therapies. This work includes developing and testing implantable devices to predict, monitor, and disrupt seizure activity.

Dr. Franck KalumeDr. Franck Kalume

To study Dravet syndrome, Dr. Kalume and collaborators at the University of Washington developed a mouse model that closely mirrors the primary symptoms and comorbidities of human patients. The mice have conditional knockouts of SCN1A, which encodes the sodium channel NaV 1.1. The model is ideal for investigating Dravet syndrome because seizures can be reliably triggered by acute increases in body temperature. Using this model, Dr. Kalume’s team found that dysfunction of GABAergic interneurons is primarily responsible for the disease presentations. They used the model to map the brain regions responsible for specific symptoms.

To study epilepsy related to Leigh syndrome, Dr. Kalume collaborates with Dr. Simon Johnson, who uses Ndufs4 knockout mice as a Leigh syndrome model. Dr. Kalume’s group developed a mouse model in which Ndufs4 is knocked out in only GABAergic interneurons. This model isolates the epilepsy component of Leigh syndrome from other aspects of the disease. The Kalume lab is using the specialized Ndufs4 mice to study epilepsy in Leigh syndrome, including identifying potential therapeutic targets.

Using these advanced models, Dr. Kalume is developing an implantable, multimodal medical device for pediatric epilepsy patients. The device monitors waking and sleeping status, cardiac and respiratory rhythm, and brain activity using electroencephalogram (EEG) technology. With these biometrics, the device will detect signs of seizures and SUDEP to provide early warnings for these events. The device could respond to early signs of seizure onset with electrical stimulation to disrupt the progression of an attack.

Dr. Kalume is interested in partnerships that use his specialized animal models and expertise on pediatric epilepsy to further the development of epilepsy-focused medical devices.

Dr. Franck Kalume’s Faces of Research Video

Stage of Development

  • Pre-clinical in vitro and in vivo

Partnering Opportunities

  • Collaborative research opportunity
  • Sponsored research agreement
  • Consultation agreement

Publications

  1. Bolea I, Gella A, Sanz E, Prada-Dacasa P, Menardy F...Kalume F, Quintana A. Defined neuronal populations drive fatal phenotype in a mouse model of Leigh syndrome. Elife. 2019;8. pii: e47163. doi: 10.7554/eLife.47163.
  2. Williams AD, Kalume F, Westenbroek RE, Catterall WA. A more efficient conditional mouse model of Dravet syndrome: Implications for epigenetic selection and sex-dependent behaviors. J Neurosci Methods. 2019;325:108315. doi: 10.1016/j.jneumeth.2019.108315.
  3. Kalume F, Oakley JC, Westenbroek RE, Gile J, de la Iglesia HO, Scheuer T, Catterall WA. Sleep impairment and reduced interneuron excitability in a mouse model of Dravet Syndrome. Neurobiol Dis. 2015;77:141-54. doi: 10.1016/j.nbd.2015.02.016.
  4. Kalume FSudden unexpected death in Dravet syndrome: Respiratory and other physiological dysfunctionsRespiratory Physiology & Neurobiology. 2013;189(2):324-328.
  5. Cheah C, Yu F, Westenbroek R et al. Specific deletion of NaV1.1 sodium channels in inhibitory interneurons causes seizures and premature death in a mouse model of Dravet syndromeProceedings of the National Academy of Sciences. 2012;109(36):14646-14651.
  6. Catterall W, Kalume F, Oakley J. NaV1.1 channels and epilepsyJournal of Physiology. 2010;588:1849-59.

Learn More

To learn more about partnering with Seattle Children’s Research Institute on this or other projects, please contact:

Dr. Elizabeth Aylward, Director 
Office of Science-Industry Partnerships 
Seattle Children’s Research Institute 
818 Stewart Street, Suite 603
Seattle, WA 98101
Email
206-884-1065