What is the University of California, Irvine Center for Neurotherapeutics?
The University of California, Irvine Center for Neurotherapeutics is a new Center formed through the support of the Vice Chancellor for Research and five different schools: Medicine, Pharmaceutical Sciences, Biosciences, Engineering, and Physical Sciences. The UCI Center for Neurotherapeutics brings together researchers from the fields of biomedicine and the physical sciences and engineering in order to facilitate the integration of physical science expertise into ongoing efforts in translational neuroscience and neurotherapeutics, with the ultimate goal of fostering drug development.
Challenges to drug development in the 21st Century:
What are the main barriers to success? Where are the bottlenecks?
Despite incredible progress in mapping the human brain and coming up with cutting edge techniques for studying its function, most basic researchers are NOT comfortable with the paradigms and approaches required for going from high priority targets to drug therapies. The goal of the UCI Center for Neurotherapeutics is to empower UCI faculty to successfully pursue more sophisticated translational neuroscience research, which will ultimately lead to novel drugs that will form the basis for new therapeutic opportunities in the neurological disease field. The UCI Center for Neurotherapeutics will promote neurological disease drug discovery by creating a Drug Discovery Unit and a CNS Delivery Program.
Drug Discovery unit
Once a researcher identifies an attractive pathway or target, the next step in therapy development often involves identification of compounds that modulate the target or pathway. The process of moving from target/pathway to small molecule drug compounds that can ultimately be used in human patients is daunting to most investigators working in an academic environment. To accelerate such research, the Drug Discovery Unit will offer support through three different core functions:
- High Throughput Screening (HTS) program – We will work with UCI investigators to develop high-quality, reliable, and reproducible assays to be deployed for identification of novel chemical matter by creating a resource center staffed with expert HTS scientists who will fabricate and validate assays appropriate to the task at hand.
- In silico screening – We will perform computational chemistry on promising targets to identify novel chemical matter to set the stage for entry into a therapy development pipeline.
- Medicinal chemistry “hit-to-lead” support – Once HTS assays and/or in silico screens yields hits, we will work with PIs to take hits from in silico screening work forward via structural modeling, and coordinate structure-activity-relationship analysis to derive compound series from “hits”.
Projects will be selected for research support and performance of this drug development work at the UCI Center for Neurotherapeutics through a solicitation of projects with established translational research targets and pathways via a RFA mechanism. The first series of RFAs will be released in October 2022.
CNS delivery program
For progress in translational neuroscience research to lead to the development of effective therapies, there must be a concerted effort to integrate bioengineering and other physical science disciplines into the realm of translational neuroscience. Nowhere is the need greater for application of physical science approaches to neurotherapeutics research than in facing the challenge of achieving high-level delivery of small molecules and biologicals across the blood-brain barrier to the CNS. While small molecules can be tailored by medicinal chemists to penetrate the blood-brain barrier efficiently based upon the inclusion of certain chemical features and group modifications, a more vexing challenge is the problem of delivering biological agents to the CNS. Because of stunning advances in genome editing, powerful techniques are emerging to treat a wide range of diseases, but these approaches are mostly limited to disorders involving the hematopoietic system or liver. If we are ever to reap the benefits of genome editing as a treatment for neurological and neurodegenerative diseases, then we must tackle the problem of how to deliver biological agents efficiently across the blood-brain barrier.
We will provide funding support to seed novel interdisciplinary multi-PI projects that include at least one biomedical school faculty member and one physical sciences / engineering school faculty member for studies aimed at developing approaches for achieving delivery of therapeutics across the blood brain barrier. The first series of RFAs will be released in October 2022.