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The WoundCure Gene Chip Could Help Treat Costly Chronic Wounds

Chronic wounds are some of the least-known and most expensive medical problems in the US.
Researchers Dr. Manuela Martins-Green (center) and PhD candidate Sandeep Dhall (left) and undergraduate Monika Garcia checking out the WoundCure gene chip in the lab. Image courtesy of the researchers

The chronic wound isn't the most attention-grabbing medical condition, but it sure is costly. According to a 2009 National Institute of Heatlh study, bed sores (pressure ulcers, for example), diabetic foot ulcers, leg ulcers, and other related chronic wounds affect 6.5 million patients, with treatments costing in excess of $25 billion. Those are major healthcare dollars. The same NIH study identified chronic wounds as having an "immense economic and social impact" on the country.

Dr. Manuela Martins-Green and PhD candidate Sandeep Dhall, both researchers at the University of California-Riverside, are aiming to revolutionize this area of medicine with the WoundCure gene chip, which would make more accurate diagnostic tests of chronic wounds possible. Physicians and insurance companies currently play a sort of numbers game that results in wasted time and money. When run through computer software, the WoundCure chip's genetic data could point doctors toward the most effective treatment, saving time and money, while reducing patient suffering.

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I spoke with Dr. Martins-Green and Dhall via Skype to discuss their WoundCure Microryza crowdfunding effort, and to get a few more details about where they're at with the project.

Motherboard: How did the WoundCure project get started?

Manuela Martins-Green: I am a wound healing biologist, working in this area for 25 years. I decided I was ready to tackle what happens when things go bad and wounds become chronic, so we can reverse course. That's when Sandeep came on the scene, and we began studies in the lab on mice and found that if we manipulated a wound in a certain way, instead of it healing we could make it go chronic. This became a model for studying chronic wound development, which doesn't exist anywhere but in our laboratory.

This is a major change because we can now enable wounds to heal properly. We can understand the difference between wounds that heal well, those that heal poorly, and those that don't heal, and that's where we are right now. So with the WoundCure chip, we want to look at the genes that are expressed and not expressed, and which are critical for the physician to look at. The people who tend to get these wounds have diabetes or bed sores from being paraplegic or bedridden—conditions that favor the development of chronic wounds.

Sandeep Dhall: I am a PhD student, and I started working in the lab trying to look at oxidative stress of this particular mouse model that was studied in Dr. Martins-Green's lab. We were trying to prove that these mice have a lot of oxidative stress in the wounds and have improper healing, which represents similarities with the healing of humans.

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So, WoundCure would allow physicians to see if a particular chronic wound needs a minimal type of treatment, or something more aggressive?

Martins-Green: Right. Sometimes you need to be more aggressive, but the reality is that physicians have restrains in assessing that. They can only empirically decide if they are going to do this or that. If they decide a wound requires an aggressive treatment, they then go to the insurance company, which will say, “Well, you don't have enough evidence that you need to proceed to that aggressive, expensive treatment… let's start with the initial treatment to see what happens.” Meanwhile, what happens is that the patient goes through treatment after treatment to arrive at the right one.

There is a lot of wasted money and a great deal of suffering this way. We are looking to find a way to identify genes, molecules, and proteins that give the physician a clue as to whether a wound can be treated with standard procedures, or whether it requires a more aggressive treatment.

A close-up of the WoundCure gene chip, courtesy the researchers

How does WoundCure provide that clearer picture?

Martins-Green: You put the DNA of each gene on a chip and collect tissue from the wound. Then prepare the tissue in a special way, and hybridize the extract of the tissue with the DNA on the chip, and find out what genes are altered. The only thing that is a little different is that the genes would be on a chip ready to go. This would be akin to having a test in a laboratory that does analysis that is ready to go for when the sample arrives.

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What will the chip look like?

Martins-Green: It's just a little device a bit like a slide used with a microscope. In the chip is a little well that contains the genes.

Dhall: The image on the Microryza site with all of those colorful dots, those are different genes that show up when you zoom in. It shows you each gene getting regulated or not regulated. In the case of our chip there would only be 12 genes or so, not all the genes shown in that picture.

Martins-Green: If the expression of the gene is elevated, it will show red. If it's not regulated, it will show green. If you use the chip with a wound, the prediction is that the more red the more serious the wound will be.

In cases of diabetes and amputation, I assume that the chip would be a strong preventive measure, no?

Martins-Green: Yes, absolutely. There are a lot of amputations in this country, and that's one thing we're trying to prevent.

Would hospitals be equipped with WoundCure chips, or would tissue samples be sent off to labs?

Martins-Green: Ideally, it would be a test in a laboratory. But, in fact, if we can develop a chip like this that can be commercialized, then I'm sure there would be some companies that would produce these chips that could then be used by laboratories or other specialized facilities that could analyze it. I'm not saying that I would start the company, because I'm a scientist. But, somebody else could.

These things are being done in other situations. In the case of cancer, for example, there is a 17-gene chip for prostrate cancer, which has been very instrumental in determining if the cancer should just be watched or treated right away. In the case of the chronic wound, it's very complicated and there was no animal model for it until our study.

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Do you think something like WoundCure's diagnostic accuracy would lower healthcare costs?

Martins-Green: I could imagine that, yes. Someone should be looking at the effectiveness of this. That is, how can it reduce healthcare costs, suffering, and morbidity. Diabetes doesn't just occur in old people; it's occurring more and more in young people. The physiology of diabetes causes these chronic wounds because one of the things diabetics don't have is a good nervous system—they don't have very good sensitivity in the extremities. They put on shoes and don't really know the shoe is bugging them; and by the time they realize this, they're already sore. And because they have altered physiological conditions, the wound is not going to heal.

So where will the funds from the Microryza campaign go?

Dhall: The licenses for using the software to analyze the gene chips are expensive. Companies have millions of dollars to buy and run those licenses, which is pretty difficult for us to do on our own.

Martins-Green: We are raising funds for something that we think has a high chance of succeeding. But, unfortunately, with the tight money these days at NIH (National Institute of Health), they don't want to take risks. They want an almost 99.5% chance that it's going work, and then they will give you the money. What will happen if we get this chip to identify these genes is that NIH will for sure give us more money to improve it. For the initial sets of experiments, though, we need the money.

So the goal is to do the research, which will hopefully get NIH's attention?

Martins-Green: Exactly. We need to initiate a different way of looking at wounds, and then improve it.