|Psoriasis (Photo credit: Wikipedia)|
Psoriasis involves the abnormal production of skin cells due to a cascade of inflammatory responses which are triggered by Tumor Necrosis Factor (TNF) and Interleukin-22 (IL-22). These cytokines (cellular chemical signals) are responsible for the inflammation (redness of the skin) seen in early stages of the condition and sets the tone for disease progression. Greater the trigger greater would be the cellular response and thus, severe the condition in the patient. Treatments of psoriasis with topical ointments or medications usually begins at an elevated level of inflammation, which basically means that the treatment is lagging far behind the cause of the condition. It is no surprise then that psoriasis cannot be cured and is only treated symptomatically.
|Role of cytokines in development of psoriasis. TNF and IL-22, the major contributors are marked in RED. |
What we really need is a method to counter this inflammation soon after it is initiated. Luckily, the human body works on something called a feedback mechanism. To every event in the body, there is a response in the form of a chemical (enzyme, hormone, cytokine etc.) released and for every release there is a built mechanism to counter it and negate the effect. The cycle continues till a normal equilibrium is reached and stays so until another trigger sets it in motion. Cytokines IL-4 and IL-10, contribute largely to this feedback mechanism which can help in reducing the inflammation but in psoriasis patients, the feedback mechanism is somewhat faulty and cannot keep the inflammation in check. The solution to this problem does not lie in developing new drugs or combinations thereof, but in tackling the root issue of producing the anti-inflammatory molecules such as IL-4 and IL-10.
For most part of the past 100 odd years that we have known about genes and genetic diseases, we have thought of them as incurable. But recent advancements in gene therapy have provided promising results in alleviating patients of their genetic conditions. Success stories of clinical trials for genetic treatments of Hemophilia, Leber Congenital amaurosis and a few other conditions have increased our confidence in treating genetic conditions and paved way for future therapies.
But it is not so straight forward either. So far, gene therapies have focused on diseases caused by the loss of function of single gene. Hemophilia B for example. Caused by defects in gene for Factor IX clotting factor. Deliver copies of Factor IX into the patient and some amount of factor IX can be produced, leading to reduction in spontaneous bleeding.
But for the condition like psoriasis, there is no absent component. There is no recognized faulty gene. All we know is that a couple of cytokines are triggered and present in excess concentrations. What is needed is a system which can detect not one but two molecules at the same time. Computer scientists call this an AND gate and use it regularly to get certain outputs in computing/ electronics. A simple example for this would be working of a microwave. A microwave works if you press the Start button AND if the door is closed. It basically means that the system responds (Q) if both signals A and B (as shown in the figure) are present at the same time.
Researchers at the Department of Biosystems Science and Engineering, ETH Zurich led by Martin Fussenegger, were successful in creating a cellular gene circuit which responds like an AND gate. They injected this gene circuitry in mice in specialized cellular capsules and used a special drug so that the mice produced TNF and IL-22. The gene circuit then responded in the presence of these two cytokines and instructed the cells to produce IL-4 and IL-10 to reduce the inflammation. Mice which did not have the gene circuitry did not show reductions in the level of inflammation. The gene circuitry enables the mice to respond at the early stage, at the cellular level, way before the symptoms appear on the skin.
The cure for psoriasis may still be far away but research findings such as these are harbingers of hope for many other inflammatory diseases as well. In the future, treatments could include injecting gene circuits that can do much more than detect one or two markers alone and this is good news for patients of cancer too.
Schukur L, Geering B, Charpin-El Hamri G, & Fussenegger M (2015). Implantable synthetic cytokine converter cells with AND-gate logic treat experimental psoriasis. Science translational medicine, 7 (318) PMID: 26676608