Understanding Disease Pathobiology Will be Key to Developing Cell Therapies for Autoimmune Disease

Bruce Cree, MD, PhD, MAS

This is the fifth part of an interview with Bruce Cree, MD, PhD, MAS. For the first part, click here. For the fourth part, click here.

For decades, the exact root cause of sickle cell disease (SCD) was known. Although, it wasn’t until late 2023 that FDA cell therapies that address this root cause, exagamglogene autotemcel (exa-cel, marketed as Casgevy) and lovotibeglogene autotemcel (lovo-cel, marketed as Lyfgenia), were developed with this knowledge and approved by the FDA.

Unfortunately, the pathobiology of some autoimmune diseases is less well understood. For example, multiple sclerosis (MS) is thought to be driven by the presence of tissue-resident pathogenic B-cells, but this is just a hypothesis. In the final part of a multipart interview with CGTLive®, Bruce Cree, MD, PhD, MAS, a professor of neurology and the clinical research director of the University of California San Francisco (UCSF) Multiple Sclerosis Center, discussed the importance of further research into the root cause of MS and other autoimmune diseases to support the development of novel treatment methods like cell therapy for these diseases.

CGTLive: What else would you like to share about researching the potential of cell therapy for autoimmune diseases?

Bruce Cree, MD, PhD, MAS: As interesting as all of this is, there's still so much work that we have to do that is basic science oriented to understand the pathobiology of the disease(s). We’ve talked a fair amount about tissue resident B-cells in MS today, and that's one theory, but it's not proven. We have to keep an open mind about what we don't know about and make sure that in addition to moving forward with these types of trials that we are really pushing forward with other avenues of research to help us understand the pathogenesis of the disease. Only once we truly understand how a disease occurs in the first place—what is driving that disorder—are we going to really be able to get to the point where we can actually reverse that problem and cure the disease.

I'll give you an example of this, and again it’s kind of a cell-based therapy. If you think about SCD, we've known exactly what causes SCD for decades, but we couldn't do anything about it. We knew exactly what the problem was down to the X-ray crystal structure of hemoglobin—but we had nothing to do and we had nothing to offer these patients, until very recently we were able to use gene-editing and now we have the capacity to cure these patients of SCD. This is an incredible step forward. We wouldn't be able to do that if we didn't understand the fundamental deficit in the disease.

At this point, we still don't understand the fundamental deficit in MS, for example, and what drives progressive disease. Maybe it's those CD19-positive B-cells in the central nervous system? That's only one idea; there are many other ideas. We have to continue to very actively advocate for basic biology to understand these conditions. This is so important when we have to advocate to the people who are in control the purse strings. It's not going to be industry that does this, this has to be done through the National Institutes of Health (NIH) and other organizations and we have to advocate for better funding for basic science to help us understand the fundamental immunobiology of these disorders in order to develop therapies that really are going to treat them and cure them.

This transcript has been edited for clarity.