Dr. Xianmin Zeng is an associate professor at The Buck Institute for Research on Aging. Dr. Zeng joined the Buck Institute in 2005. Her laboratory focuses on potential treatments and therapies for Parkinson’s disease. Before arriving at the Buck Institute, Dr. Zeng earned a PhD in Molecular Biology at the Technical University of Denmark followed by postdoctoral training on embryonic stem cells at the National Institutes of Health. After establishing her laboratory, Dr. Zeng was awarded a prestigious grant from the California Institute for Regenerative Medicine to spearhead the development of a stem cell-based treatment for Parkinson’s disease. After years of dedicated work creating the cell lines and collaborating on a delivery system the Zeng laboratory and their industry collaborators have developed a stem cell based treatment that is ready for human clinical trials.
This “new treatment” relies on a specialized process to make and purify nerve cells from induced pluripotent stem cells which can be implanted into humans. In the process of creating the iPSCs (induced pluripotent stem cells) multiple patient lines were also created resulting in an invaluable resource of a wide variety of Parkinson’s patient lines, many of which are now available for purchase by other research laboratories. Having this vast variety of patient lines allows researchers to better understand the different mutations that can cause Parkinson’s disease.
Dr. Zeng’s talk focused on the process of creating this potential stem cell-based treatment for Parkinson’s disease. During therapy development, Dr. Zeng formed a company, XCell Science Inc., to create and maintain all of the patient-specific lines along with the potential allogeneic (cells from a universal donor) treatment lines. An allogeneic line is one that can be used in multiple patients, these donors are screened for any disease or mutations and are “compatible” with a subgroup of patients, much like how organ donation works. Dr. Zeng expects these cells lines to soon be entering clinical trials. One challenge with Parkinson’s disease lies in delivering the desired treatment to the brain. These cells are able to populate the diseased area, differentiating into the appropriate cell type and replacing the dead neurons. Dr. Zeng discussed her strategy to deliver the partially differentiated stem cells into the brain. One way in which this widespread delivery might be accomplished is to have a single injection that can be multi-pronged, reaching many areas of the brain. If this treatment works it could have a broad impact by serving as as a template to treat a variety of other neurodegenerative diseases.
Q: What was the most challenging part about creating a cGMP (Good Manufacturing Practices) cell line?
XZ: Since the line was not made at the Buck Institute the most challenging aspect was finding a facility that could work with induced pluripotent stem cells (iPSCs). This was especially challenging since the process was not optimized at the time, so we had to train people, while building the expertise to manufacture the cGMP-grade iPSCs. As an advantage, you are able to help define the standard in the field, which although challenging was extremely rewarding.
Q: What has been the most fulfilling aspect of creating the cGMP cell lines?
XZ: There are so many people to learn from in the manufacturing field, and many have even started companies. I always welcome the opportunity to learn from experts in their field. This was also an excellent learning experience, giving me a better understanding as to why some products succeeded and why others failed.
Q: You mention allogeneic donors. Could you describe what an allogeneic donor is and what the advantages are compared to a patient’s own cells?
XZ: One of the main considerations is the cost. Although the best-case scenario is having your own cells modified and implanted back into you, this is a therapy for only one person. An allogeneic donor line after being tested and verified can serve multiple patients. It is a bit like having a blood bank; one line of allogeneic cells will work for many patients, while another line of allogeneic cells will work for a different set of patients. The challenge is to calculate how many different allogeneic lines are needed to work with 90% of the patient population. This approach is beneficial as it makes the treatment available to a broad audience, while keeping the cost at a level that the company can afford to offer the treatment.
Q: When a patient receives cells as a treatment will they have to be on immune-repressors similar to how organ transplant patients have to be on immune-repressors?
XZ: Unfortunately, yes, and it will depend on which tissues are transplanted. For example the eyes and the nervous system are currently thought of as immune-privileged (meaning the immune system is not as reactive in these organs), which may reduce some of the immune response since a treatment for Parkinson’s would mostly target the brain, commonly thought of as an immune-privileged organ. However, this is certainly an area under investigation that needs to be thoroughly evaluated as clinical trials progress forward.
Q: How long do the new cells survive after the initial implantation?
XZ: It is not expected that you would need to do this treatment repeatedly. In the animal studies that we conducted the transplanted cells survived over six months. If one were to extrapolate this to human lifespan then it could be many years in which the cells will both survive and integrate into the brain after treatment.
Q: Are there any estimates on what this treatment might cost?
XZ: I’m going estimate the cost of the phase I trial and hospital costs. The operation and injection in the hospital is about $100,000. This doesn’t include the cells that are being implanted. On average running a phase I clinical trial takes millions of dollars. The commercialization and the final cost to an actual patient after the clinical studies are completed will depend partially on how successful the trials are and on how well the allogeneic donor cells are received. At this time I can’t give you a precise commercialized product cost.
Q: Could you describe the process of starting your own company XCell Science?
XZ: That is one of my favorite stories. I came to the Buck Institute in 2005, and I was one of the early people working on stem cells at Buck. I was most driven by the ability to help patients. It was not necessarily a disease-specific desire, but I wanted to help individuals. I realized that the best way to bring research to the patient was through industry. The reason to involve industry is that to run a clinical trial, which is required for a treatment to make it into a patient, a certain type of expertise and capital are needed. Academic research environments do not usually have the necessary expertise or capital, so partnering with industry becomes necessary. After founding XCell Science I was able to raise a substantial amount of capital, which allowed for the company to work with other industry partners to manufacture and commercialize our modified cells lines.
Q: When you are not writing grants, or papers, what do you do for fun?
XZ: I love to follow sports–football and basketball. I am a Golden State Warriors fan. I always cheer for the home team. To stay active I enjoy running.