California’s stem cell agency funds research into Angelman syndrome and bioprint pacemaker

UC Davis Health professors David Segal and Deborah Lieu have received Discovery Stage Research Projects (DISC2) awards from the governing Board of the California Institute for Regenerative Medicine (CIRM).

DISC2, funded through The Quest Awards Program, promotes the discovery of promising new stem cell-based and gene therapy technologies that could be translated to enable broad use and ultimately, improve patient care.

Stem cell gene therapy for Angelman syndrome

Prof. David Segal and his team work to find a cure for Angelman syndrome

Segal will receive $1.36 million to work on finding a treatment for Angelman syndrome, a rare neurogenetic condition. This disease, which affects around one in 15,000 births in the U.S., is caused by loss of ubiquitin ligase E3A (UBE3A) gene expression in the brain. It leads to severe developmental delay, loss of control of bodily movements, and epilepsy.

Currently, there are no treatments for Angelman syndrome. Segal and his team are researching AAV9-Cas13 gene therapy that will deliver a targetable RNA nuclease (Cas13) to the brain to safely and permanently restore expression of UBE3A deficient in the neurons of the central nervous system.

“This therapy uses a first-of-its-kind mechanism to bring much-needed new treatments that could directly benefit around 2,500 children and families living with Angelman syndrome in California and many more globally,” Segal said.

Segal is a member of the UC Davis Genome Center and a faculty member at the UC Davis MIND Institute. He also holds joint appointments in the Departments of Biochemistry and Molecular Medicine and Pharmacology.

Building a biopacemaker

Over 350,000 patients a year in the U.S. require an electronic pacemaker to restore their heart rhythm. The annual healthcare burden amounts to $20 billion. Repeated surgeries to replace battery and electrical parts generate additional costs and suffering for patients.

Dr. Deborah Lieu and her team work on developing bioengineered pacemakers

Deborah Lieu, assistant professor of cardiology, was granted $1.4 million to develop a bio-pacemaker by bioprinting hiPSC-derived cardiomyocytes (cells responsible for control of the rhythmic beating of the heart) and fibroblasts (cells that secrete collagen proteins used in connective tissues).

Human-induced pluripotent stem cell (hiPSC) is a type of cell taken from human tissue (usually skin or blood) and genetically modified to behave like an embryonic stem cell. It has the ability to form all cell types, including the capacity for self-renewal and differentiation into cardiac myocytes.

“The bio-pacemaker has the potential to overcome limitations associated with electronic pacemakers, improve the quality of life for the pacemaker recipient, and reduce the cumulative health care costs,” Lieu said.

This highly interdisciplinary research brings together a team of UC Davis investigators, including Prof. Kent Leach from Biomedical Engineering, Prof. Nipavan Chiamvimonvat from Cardiology, Prof. James Chan from Pathology and Laboratory Medicine, and Prof. Jan Nolta, director of the Stem Cell Program.

The proposed project was praised by the reviewers for its creativity and innovation. It could deliver a proof-of-concept in two years.

Watch a video of Dr. Deborah Lieu explaining the “Quest for Pacemaking Cardiomyocytes to Engineer Biopacemakers.”