COMMENTARY

Creating Human Tissues to Test Drugs for Rare Diseases

Marshall L. Summar, MD; James C. Powers

Disclosures

January 20, 2015

Editorial Collaboration

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Marshall L. Summar, MD: I am Marshall Summar, Chief of Genetics and Metabolism at Children's National Medical Center in Washington, DC, for Medscape Rare Diseases.

I am at the National Organization for Rare Diseases (NORD) Orphan Products Breakthrough Summit with Jim Powers, the CEO of HemoShear (Charlottesville, Virginia). Jim's company is leading some of the technological revolutions in rare diseases, and we are going to talk about what is going on.

In dealing with rare diseases, we don't have a lot of patients for clinical trials and clinical studies, and one of the holy grails of genetics has been finding tissue models that are relevant to study. Could you tell us about the technology that your company is developing, and how it will help?

James C. Powers: It will probably help for me to describe what our basic technology is, and then talk about the rare diseases applications. Our company creates human tissue systems that accurately replicate human diseases in the laboratory. When you think about some of the technological innovations that have happened over the years—high-throughput screening, combinatorial chemistry, analyzing the human genome—we still lack systems in the laboratory that accurately replicate human disease and that can predict whether a new drug candidate will work in a human. That is the problem that we are trying to address.

Dr Summar: One of the things we hear thrown about is the idea of the "human on a chip" for drug testing as a way to accelerate the process. Is this more like a "human on a plate" at this point—an intermediary step?

Mr Powers: It is. The difference is that the construct of our science is more robust, in terms of having more tissue material for a scientist to understand what is going on about the biology, how the disease works, and what genes and proteins regulate disease in a system—in order to fully understand a drug response in a more robust way than, perhaps, the tissue on a chip system does.

Dr Summar: This is a little bit different from your classic pharma-type research. Not only are you trying to test safety and efficacy, and maybe identify new compounds, but also you are looking at the basic molecular pathophysiology of these diseases in these cell lines.

Mr Powers: We can, and that is the starting point—to recreate the disease biology and understand the meaningful targets. Typically, today, scientists find targets from all kinds of sources, including animals, that are not necessarily relevant to humans. So we start by getting on the right path and identifying meaningful targets that play an important role in disease progression—and by getting on the right path, we have a better chance for success of the new drug candidate.

Dr Summar: You bring up an interesting point. We have been doing mouse studies for years, and we have found lots of ways to make mice better and fix mice. But what we have found is that biochemically and genetically, mice and humans aren't quite the same and don't behave the same. Does this provide a bridge that is a little closer to the human model? Is that what you are getting at?

Mr Powers: It absolutely does. You could ask, why study the disease in an animal at all if the animal doesn't develop the disease? That is certainly the case in rare diseases. It is hard to put a human rare disease in an animal. We believe that, to some extent, we can leapfrog animal studies and go straight to assessing biology in a human-relevant context using human tissue.

In the end, we still need animals, because those are the requirements for safety that still need to be satisfied before we take a new drug into humans. But we feel that we have a better system in terms of recreating the human disease biology in the bench.

Dr Summar: This is very exciting technology. It sounds like you may develop an accelerator program for looking at compounds. What kind of tissues can you currently recreate?

Mr Powers: Our expertise was originally in the vascular space, so we can recreate regional vascular biology in any part of the human body, as well as in a whole host of vascular diseases, including rare diseases. We began to appreciate how important those principles of flow were. Every cell and organ in the body has either blood or fluids moving through it, so those principles are extremely important to restoring human tissue biology. We used those to move forward and create disease models, and we found that the principles of flow are certainly important in vascular biology (the biology of the human blood vessel system).

Next, we used those principles to restore the biology of liver tissue on the bench. That happens to be the focus of a collaboration that we will have in the near future with Children's National Medical Center to begin to explore liver-focused rare diseases with the HemoShear science and in combination with Children's own clinical expertise.

Dr Summar: This is a very exciting technology, and I appreciate you coming in and speaking with us about it.

Mr Powers: You are welcome. It is a pleasure being here.

Dr Summar: And to our listeners, these are some of the things that are going on in the rare diseases field as we continue to figure out how to get drugs and therapies to our patients faster, but also increase our basic biological understanding of rare diseases. This is one of the ways that the field is moving forward.

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