Global Science Summit: Pillar 1 Sneak Peek

The first talk will be given to us by Dr. Barbara Bailus at Keck Graduate University discussing novel cell penetrating peptides (CPPs) designed to enhance therapeutic delivery to the brain. As discussed last year, one of the challenges faced in developing therapeutics targeted for the brain is crossing the blood brain barrier, a protective layer that allows essential nutrients and oxygen into the brain while blocking harmful substances. Dr. Bailus has developed cell penetrating peptides that act as a “backstage pass” enabling therapies to cross the blood brain barrier. This year, we anticipate learning more about the development of the CPPs and their efficacy in helping move therapeutic candidates across the blood brain barrier in cell and mouse models.

The second is on a hematopoietic stem cell gene therapy (HSC-GT) using a lentiviral vector to deliver UBE3A that will be given by Chris Luthers, a Doctoral student working with Dr. Donal Kohn at the University of California, Los Angeles. Last year, we heard about how HSC-GT could work in AS by Jennifer Panagoulias, where a sample of a patient’s own blood cells are removed and treated with the modified UBE3A gene. Those cells would then be infused back into the patient, migrate back into the bone marrow, and produce UBE3A-expressing immune cells that cross the blood brain barrier and provide functional UBE3A in a process called cross-correction where the UBE3A protein can be secreted and taken up by many neurons in the area. Last year they were designing animal studies to understand safety, distribution throughout the brain, and length of effect as they were preparing for IND-enabling studies, and we are looking forward to seeing how those studies have progressed.

Finally, we are eager to hear an update from Dr. Nadav Ahituv at the University of California, San Francisco who is working in collaboration Drs. Albert Keung and Yong-Hui Jiang on a CRISPR activation strategy designed to upregulate critical genes outside of UBE3A to assess how they may contribute to AS symptom severity. Last year, this project had just received funding from FAST and we learned about the basic experimental design including which genes are being targeted for up regulation, how they planned to design constructs for both single gene and multiple gene upregulation, and potential next steps for both in vitro and in vivo model testing. We expect to see updates on single and multiple gene candidates' ability to upregulate target genes and hear about the next in vitro and in vivo steps of efficacy.

Dr. James Willson will be presenting an update on GTP-220: A Gene Replacement Therapy for Angelman Syndrome.