David Spencer, MD, director of the Comprehensive Epilepsy Center and professor of neurology at Oregon Health and Science University, discusses the importance of patient safety in a first-in-human trial of NRTX-1001 GABAergic interneuron cell therapy for focal epilepsy.
A first-in-human clinical trial of NRTX-1001, an investigational treatment for epilepsy, has 3 main areas of possible risk. But patient safety is the main focus, explained David Spencer, MD, director of the Comprehensive Epilepsy Center and professor of neurology at Oregon Health and Science University.
Can you provide more information on the potential risks associated with interneuron cell therapy for treatment of focal epilepsy, and what measures are being taken to ensure patient safety during the clinical trial?
This trial is really focused on safety. That's the primary focus of the trial. We understand quite a bit about the potential risks from all the work that’s gone into developing the therapy and using it in animal models of epilepsy, and just the accumulated knowledge about managing cell cultures and cell therapy in general, which has kind of been cross fertilized by work in other fields.
In this trial, I'd say there's probably three main areas of potential risks that we focus on when we talk to people about whether they want to participate. One is, we have to get the cells into the seizure focus. So, the implant procedure is done, in under very controlled conditions in the operating room. We use MRI guidance to make sure we get from directly onto the target and cells are delivered just through a very small opening in the back of the skull. And the surgeon will place a probe into the seizure focus and deliver the cells through that, remove the probe, and then patients recover generally overnight and go home the next day. So, it's not a prolonged recovery. [It’s] kind of amazing actually how this can be done; pretty minimally invasive.
But anytime we take that approach to, to go to the seizure focus to deliver the cells, there is some small risk of bleeding or infection. So, just the procedure itself of getting the cells there has some small risks associated with it. Looked at very carefully to try to determine what are the risks of putting new cells into that part of the brain, the biggest concern being [that] true stem cells are cells that have the capacity to divide and develop into different cell types. So, one of the things that we have to be very cautious about is to make sure that these cells don't divide or grow or turn into a tumor of some kind, and cells being used in this study and in this form of therapy are what we call postmitotic cells. They no longer have the capacity to divide and replicate. The cells have to be screened very carefully to make sure none of those dividing stem cells are still in the cells that are being implanted. This has been looked at very, very carefully in multiple animal models of epilepsy in pre-clinical trials, which has looked very favorable. In in the two people that have participated so far, we've seen no concerns and no problems in that area, but it's a theoretical concern that we watch for.
And then finally, the third one is the risk of immunosuppression. In a sense, there are human cells being implanted into the seizure focus, but it's not the patient's own cells. It's, in a sense, a transplant, so like other organ transplants, somewhat similar, people do have to be on immunosuppression for a period of time to make sure that their immune system doesn't reject the cells that are being implanted and that they have a chance to integrate and develop connections and be recognized as part of that person's body. So we’re thinking at least a year of immunosuppression is needed. So with that, it’s monitored extremely carefully, but again, carries some potential risks for infections.