Sophisticated research capabilities, big data accelerate discoveries of mechanisms, drug targets

December 22, 2014

Research has become much more sophisticated in recent decades; however, gaps remain in the understanding of how to treat common problems, like warts, researchers say.

Dermatology research is in high gear in high-tech areas but gaps remain in the understanding of how to treat common problems, like warts, researchers say.

Research has become much more sophisticated in recent decades, says Kevin D. Cooper, M.D., a dermatology researcher since the late 1970s. He is professor and chair of dermatology at Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio.

The ability to answer questions in a definitive way and in a way that results in treatment advances or diagnostic advances is much better now,” he says.

What does that mean to dermatology? Dr. Cooper says it means accelerated discoveries of new mechanisms, drug targets, drugs and repurposed drugs. It means an explosion of available data and what we can do with it.

“… the breadth of research that dermatologists and cutaneous biologists do is much greater,” Dr. Cooper says. “You can start from a very small genetic mutation and one molecule or comb through giant data sets to figure out novel comorbidities and linkages that skin diseases may have that we didn’t recognize before.

Starting at the molecule

Genetic research is advancing in dermatology, uncovering not only the source of disease but ways in which to correct it at the genetic level. 

Now there are studies that show we can replace a protein or put cells into a child who has a genetic defect, let’s say a blistering disease defect,” Dr. Cooper says. Clinical trials are in process, and those therapies are being studied now to determine practicality. If they are efficacious and safe, they’ll help kids and may lay the groundwork for other cell-based or protein therapies for other diseases.

Research analyzing the entire human genome is phenomenal, according to researcher and dermatologist Steven R. Feldman, M.D., Ph.D., professor of dermatology, Wake Forest University School of Medicine, Winston-Salem, NC.

I anticipate that [researchers] are going to keep finding, through genetics, a better understanding of diseases like psoriasis and alopecia areata that will transform our understanding, if not the treatment, of those conditions,” Dr. Feldman says.

Today's dermatology researchers are not only coding for certain genes and alterations of RNA molecules that code for proteins, but they’re also looking at how non-coding RNAs regulate how cells work. It’s more akin to epigenetics-changes brought on by the cellular environment that causes genes to be turned on or off over time, according to Dr. Cooper.  This area of study, according to Dr. Cooper, is likely to affect inflammatory diseases, including psoriasis and eczema, as well as diseases acquired with age, such as photoaging and skin cancers. 

I don’t think we’ll see any such new therapeutics next year but it’s an area that’s being studied pretty intensively because it offers new opportunities with intellectual property and the ability to target disease processes in a different way,” Dr. Cooper says. 

NEXT: Immune system modification

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Immune system modification

Melanoma research is among the areas setting the stage for a series of medications that modify the immune system or modify signaling that melanoma cells need. 

That area continues to evolve, where people are combining immunologic therapy with cell signaling therapy or boosting the immune system in another way in order to optimize combination therapies for melanoma patients,” Dr. Cooper says. 

Trying to suppress or modify the immune system is another exciting area in research.

Dr. Feldman says there’s a lot of work going on in psoriasis and inflammatory diseases, looking at comorbidities of inflammatory disease and new treatments based on a growing understanding of the immune system. Then, comes research on the marriage of those two: what the effects of those treatments are on the comorbidities of inflammatory disease, Dr. Feldman says.

With psoriasis, we’ve seen a lot of new drugs, and we’re going to see more drugs in the IL23, IL17 pathways. Those are very exciting in the sense that they’re very specifically targeted. They’re antibodies. They don’t have the toxicity of small molecules. They can reverse an altered balance, without knocking down the entire immune system,” Dr. Cooper says. 

Topical and systemic agents are being developed thanks to research looking at signaling pathways required for T-cell activation, and small molecule inhibitors for what are called the JAK-STAT pathways. These drugs allow a more nimble wash-out, if desired. While researchers don’t yet know the full implications to dermatology, there’s evidence to suggest these agents will benefit psoriasis, as well as auto-inflammatory diseases, such as alopecia areata, Dr. Cooper says.  

Basic skin research

Today's research might be sophisticated, but it continues to ask the basic question: How does the skin work? Researchers are always looking at basic interactions between cells and the skin, to identify mechanisms of those interactions and how those cells work. That knowledge helps to identify what Dr. Cooper calls “druggable” targets, as well as why it is that treatments work. 

One example of this kind of research is dermatology’s paradigm shift in atopic dermatitis.  

In atopic dermatitis, we’ve really evolved our understanding from it being primarily an allergic disease to being a barrier disease with altered microbiome, all intertwined. Now we have new therapies that are coming into atopic dermatitis as a result of that,” Dr. Cooper says. 

Stem cell researchers in the specialty continue to study stem cells’ potential to differentiate into cells needed to replace cells lost with disease or aging. Target areas for stem cell therapy include vitiligo, hair loss and aesthetic dermatology, Dr. Cooper says.

NEXT: Looking beyond the skin

 

Looking beyond the skin

The skin-nerve-brain connection is a hot topic in research, Dr. Cooper says. Among the many questions researchers are trying to answer: How does itch occur? Is it always in the skin? In the spine? In the brain? Can you test that? How do skin diseases create anxiety and depression and vice versa? If your nervous system is not working right, does that affect your immunology? Does the inflammation have a role in mood, per se?

Big data

Big data is opening big doors in genetics and other areas of dermatology. Large databases from multiple specialties, full of information about patients’ genetics, the diseases they have and the drugs they’re on are becoming the Holy Grail, according to Dr. Cooper.

Knowing the genetics of people and linking that to their healthcare outcomes over time is a very important area. We’re sort of that the beginning of that,” he says.

With access to big data, researchers should better understand many things at the practice to population levels, including which patients respond to treatments and which don’t. The result? Personalized medicine, according to Dr. Cooper.

Gaps remain

Research and research dollars need to focus on what's common in dermatology, according to Dr. Feldman.

If I could cure one thing, I would find a cure for warts,” Dr. Feldman says.

Dermatologists have little to offer patients with warts and there isn’t much in the pipeline as far as I’m aware,” he says. “We tend to put our focus on narrow scientific issues that are totally fascinating, and they highlight a greater understanding of human biology. But the real opportunities lie, I think, in much broader, more common, less ‘test-tubey’ kinds of research.” 

Seborrheic dermatitis is another example of something that seems so simple but remains elusive, according to Adam Friedman, M.D., assistant professor of medicine (dermatology)/physiology and biophysics and director of dermatologic research at Montefiore - Albert Einstein College of Medicine, Bronx, NY.

No question, a couple of patients come to the practice with it every day. We still don’t 100 percent understand how it really happens. Therefore, the treatments haven’t changed that much. I think there needs to be continuing stimulus to encourage investigators to not just evaluate if a drug is effective, but to elucidate the pathophysiologic underpinnings of the disease, itself, to better identify new and more specific drug targets,” Dr. Friedman says.

 

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