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"Speaking of Vitiligo..."

Why isn’t there a cure for vitiligo?

Monday, October 13, 2014

Man kills lawnI just finished submitting another grant application to the NIH to support our vitiligo research. It’s a long, complicated process to assemble an application, which you can read more about here. The NIH budget has decreased by about 20% over the last 20 years when accounting for inflation, which has had a very large negative impact on biomedical research, the work that will hopefully lead to much better treatments for vitiligo and, someday, a cure. We’re losing scientists every day because they can’t find the funding necessary to keep doing their work, and it’s discouraging. 

But why do we need to continue research in vitiligo – why isn’t there a cure already? We’ve learned a lot about the disease in the past 25 years, and even more in the past 5. Someone asked me recently, if we’re right about what causes vitiligo, why isn’t there a cure? Doesn’t that mean that our theory about the cause is wrong? In fact, modern medicine can’t cure most diseases, despite knowing exactly what causes many of them (think cystic fibrosis, you can read about that here). Other than diseased tissues that can be removed surgically (think appendicitis), the only curable diseases are some bacterial infections that are susceptible to antibiotics, and a small number of cancers. The reasons we can cure these diseases is that the cells that cause them are different enough from our own normal cells that we’ve found a drug that interferes with them in a very specific way.

This reminds me of how difficult it is to take care of my lawn. I would love to have a healthy, green lawn without any weeds. The challenge is to kill the weeds without harming the grass. I’m not a botanist, but I was interested in the science behind herbicides used for lawn care, and read up on them. Herbicides are generally safe for people and their pets because they specifically target important enzymes needed for growth of plant cells, but not animal cells. So it is a selective inhibitor in the sense that it is toxic for plants and not animals.

You can use a broad-spectrum herbicide on your lawn and it will almost surely kill all the weeds. The problem is that it will also kill all your grass (see what that looks like here). A selective herbicide aims to target only the weeds and spare the grass. It does this by inhibiting critical enzymes needed for growth of broad-leafed plants (dicots), but not grasses (monocots). In this way, you can spray it all over your lawn and because it is selective, it only targets the weeds while the grasses are spared. The discovery of dicot-selective toxins is actually pretty impressive science, allowing us to cure our lawn of dicot weeds. This is similar to killing a bacterium in our body, which has enzymes and other proteins that humans don’t have, which can be inhibited with an antibiotic that has no effect on human cells. Therefore it cures the infection without making us sick (unless we’re allergic to the drug, which is a completely different story).

The problem with my lawn occurs when weed grasses start to grow (like creeping bentgrass, blanket crabgrass, and others). This is a MUCH more difficult problem, because these weeds are monocot grasses, and therefore aren’t killed with dicot herbicides. The amazing scientific discovery of dicot-selective toxins does nothing for these monocot weeds, and now we’re back to square one. My options are to hand-pull the grassy weeds or destroy the entire lawn and start all over. In our analogy now with treating human diseases like vitiligo, many of the current treatments are like hand-pulling the weed grasses, while destroying the patient and starting over is not an option. Many human diseases, including vitiligo and other autoimmune diseases, are caused by our immune system working TOO WELL. It is doing its job and killing foreign organisms, but it is also causing inflammation and destroying your own normal cells. Because these disease-causing cells are part of us (and working pretty much normally), they’re like the weed grasses that use the same enzymes as the lawn grasses – they can’t be selectively targeted. 

So in autoimmune diseases like vitiligo, current treatments are like pulling the weed grasses without destroying the roots. It’ll look better for a while, but unless I continue to pull them every time just as they appear, they will just grow back. So current medicines don’t cure, they only treat, and you must continue to take them or the disease will come back. In addition, they work by partially interfering with the function of the disease-causing immune cells, but also affect those that function normally as well, which is why there are often side effects of these treatments.

You might correctly suggest that if we could learn more detail about the enzymes in grass and weed grasses we could discover new herbicides that would kill the weed grasses and spare the grass. It’s the same thing for autoimmune diseases like vitiligo. If we are going to eventually find a cure for vitiligo (and better treatments in the meantime), we need to learn a lot more about the cells and their proteins that cause it so that we can find drugs that turn off the critical pathways that drive it, but aren’t required for normal functioning of the immune system. We, and others, have recently discovered some of these pathways (read about one of them here), so we’re getting closer, but we’re not there yet. Try not to become too disappointed when our new discoveries are better treatments and not cures, because we’re trying to do a pretty difficult thing. And we’re making sure that we don’t kill the grass. Rest assured, we’re working very, very hard at it.