Genetic disease models
We are focused on understanding and treating epilepsy and neurodevelopmental disability caused by gene mutation (i.e., pathogenic variants in disease genes). Care of patients affected by these conditions, including the group of severe early-onset epilepsies known as the developmental and epileptic encephalopathies (DEE) is currently restricted to therapies that attempt to address symptoms, usually with limited results. Patients are seen by physical and occupational therapists, speech & language pathologists, and developmental specialists for their neurodevelopmental delay and autistic symptoms. In addition, they may be treated with medications to address behavioral problems and seizures. Despite these attempts, many patients remain substantially impaired, non-verbal, and ultimately unable to care for themselves when they reach adulthood.
In the Sands lab, we study a variety of mouse and human cellular models in genes that cause severe childhood epilepsies, with the goals of understanding the molecular basis of disease and devising and testing novel therapies.
Grin2d
Csnk2b
Iqsec2
Kcnq3
Grin2a
Therapies
We work with Scott Harper in the Center for Gene Therapy at Nationwide Children's Hospital (Columbus, OH) to develop and test a variety of adeno-associated virus (AAV) vectors in our mouse and cellular models. Because AAV cargo is expressed perpetually in a transduced cell, these vectors have the potential to deliver permanent therapy with a single treatment: "One-and-done." The realization of such a promise depends heavily on many factors, including research efforts in living model organisms to examine factors such as expression level, dosage, timing and unintended consequences.
