QPatch instrument grant advances UTSA’s ion channel research
Dr. Nicholas Clanton and his team at the University of Texas at San Antonio have received a QPatch instrument grant. We spoke with Dr. Clanton about what this award and access to Sophion’s automated patch clamp will mean for the ion channel research in UTSA’s Preclinical Pharmacology Core.
It’s still early days, but how has the installation, training, and working with Sophion gone so far?
Getting the QPatch 48 up in the Pharmacology Core has been a very fast process. The training provided by Sophion allowed us to begin validating our important cardiac safety assays the very next week. Applications scientist, Weifeng Yu, has been incredibly helpful in developing protocols for difficult, less common channels.
Can you walk us through the first set of ion-channel assays you plan to run on the QPatch 48, and what novel insights you hope to gain from automating these measurements?
Our primary interest in acquiring an automated patch clamp system was to bring cardiac safety screening to the Preclinical Pharmacology Core. Our main focus is in hERG screening for early-phase programs; however, we have been able to expand to other CiPA targets, including NaV1.5 and CaV1.2. Automation allows us to offer these services at a lower cost to clients, allowing them to screen a larger number of candidates earlier in the drug discovery process. This cardiac safety data can then be used to inform medicinal chemistry campaigns and “design out” any toxic liabilities before candidates get too far into preclinical development.
How will automating patch-clamp screening on the QPatch change the scale, speed, and reproducibility of your preclinical assays compared to your current manual methods?
Before the installation of the QPatch, we actually had no means to offer these important services to clients. Most of our clients are in the lead optimization phase of drug discovery, evaluating several candidates and using this data to optimize compounds through medicinal chemistry. The increased throughput and low compound requirements of automated patch allow us to handle these large programs and turn data around much more quickly, accelerating preclinical development for our clients and collaborators.
Stanton McHardy will be using the QPatch for early cardiac safety screening – how do you plan to fold those assays into your existing drug-development pipeline, and what impact do you anticipate on candidate prioritization?
Cardiac safety screening was the primary missing link in our drug development pipeline in the Center for Innovative Drug Discovery (CIDD). Previously, this had to be outsourced to CROs, often at high costs that were prohibitive beyond screening 1-2 compounds on an academic budget. With the addition of rigorous cardiac safety screening using automated patch clamp in the CIDD, we now have the resources in-house to support programs through relatively late preclinical development and even into IND-enabling studies. This will have a tremendous impact both on the prioritization of early candidates and the characterization and final selection of late-stage candidates.
Do you see this channel safety screening becoming an assay for other groups/collaborators doing drug discovery & development, even for non-ion channel programs?
Absolutely! Cardiac safety screening is a vital part of preclinical development for all programs, not just ion channel targets. The FDA recommends screening not only against hERG, but also NaV1.5, CaV1.2, and additional CiPA targets for IND submissions. We are already working with programs in cancer, infectious disease, pain, and multiple other therapeutic areas.
What new collaborations, both within UTSA (e.g., Brain Health Consortium, Stem Cell Core) and with external partners, have emerged or do you expect to emerge as a direct result of having access to this automated patch-clamp technology?
We have picked up several new collaborations since the installation of the QPatch. We are currently working with four new groups from UT Health San Antonio studying calcium, potassium, sodium-leak, and even a magnesium channel. We are also working on multiple programs within the CIDD, and two collaborators at Washington University in St. Lois (WUSTL). In addition to academic collaborations, we have also been working with local companies to provide automated patch clamp services.
One of our major collaborations at WUSTL is with Dr. Doug Frantz, Vice Chancellor for Commercialization and Innovation and former professor of Chemistry at UT San Antonio. Dr. Frantz is developing novel NaV inhibitors for the treatment of chronic pain. While we have been collaborating on this program for a few years, we previously lacked the capacity to perform the primary screen for NaV inhibition for compound evaluation. With the installation of the QPatch, we can now rapidly evaluate candidates produced by his group to push this program forward. This work is supporting the training of multiple graduate students in the Frantz group.
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