Global Science Summit: Pillar 3 Sneak Peek

The first, a talk given by Dr. Alvin Huang from Brown University, will focus on the roles of UBE3A in brain development and how these can be targeted for therapeutic development. Last year Dr. Huang discussed how the loss of UBE3A led to impaired growth in what are called oligodendrocyte progenitor cells. These cells aid in the production of myelin, which insulates neurons and helps in neuronal communication. In the absence of UBE3A, myelination is delayed, affecting the connectivity of neurons in the brain. Dr. Huang and his team performed a drug screen and found that a particular compound that acts on estrogen receptors countered the effect of impaired oligodendroglial progenitor cell proliferation caused by the loss of UBE3A. This drug was tested in a mouse model of AS where they found clear rescue of motor and cognitive behavior. We look forward to hearing about updates on this work as well as a new project looking at the role of UBE3A in autophagy, a cellular recycling process used to clear out cellular debris and maintain cell health. Their preliminary studies have shown that, when UBE3A is lacking, this recycling process becomes overly active and disrupts the balance of proteins, likely contributing to the neurological symptoms observed in AS.

The second talk will be given to us by Dr. John Marshall who is also from Brown University. Last year we heard about his work on D-Syn3, a small molecule that targets TrkB receptors known to be involved in a signaling pathway that contributes to synaptic plasticity, learning, and memory. In the absence of UBE3A, these signaling pathways are disrupted and drugs like D-Syn3 are designed to enhance the signaling events necessary for typical neuronal function and learning and memory. We saw last year that the administration of D-Syn3 in a mouse model of AS resulted in motor, cognitive, and seizure susceptibility rescue, indicating the therapeutic potential of using a compound like D-Syn3 to target TrkB signaling. We look forward to updates on the progress of D-Syn3 as a potential therapeutic and what next steps may look like.

Nancy E. Jones, PhD will be presenting an update on NNZ-2591.

Joerg Hipp, PhD will be presenting an update on the Alderbaran study.