When we were in the third year of our studies at UCL we particularly enjoyed one of our modules on stem cells and regenerative medicine. At the very beginning of this module we were warned that
despite the fact that this field of science is full of fascinating and promising research, it is crucial to
stay cautious and take all the results with a pinch of salt as there are still lots of unknowns and fraud.
Today we would like to talk about one of the most promising research in regenerative medicine that
has already shown amazing results and led to a patent of a drug that cures chronic wounds. So, without further ado we present an innovative approach that has shown to promote healing of chronic wounds.
Normal wound healing
Our skin is the biggest organ in our body and its primary role is to guard us from pathogens, chemical and physical aggressors. Health and integrity of the skin is paramount, therefore, when our protective barrier is injured our organism immediately enters a state of emergency and concentrates on restoring and revitalisation of the damaged tissue.
The process of wound healing is complex and super efficient, which involves four key stages. The key events of the main stages of wound healing are summarised in the infographics below.
Unfortunately, in some cases the normal wound healing is compromised due to a genetic predisposition or chronic conditions like type 2 diabetes, which could lead to the development of chronic wounds. It is also important to bear in mind that with age body’s ability to heal wounds rapidly decreases, leading to the development of chronic wounds in elderly.
When it comes to chronic wounds like venous leg ulcers and diabetic foot ulcers, there is a growing
need in developing treatments. Chronic wounds fail to close and heal in an orderly and timely manner, which causes lots of discomfort to patients. To date, treatment of chronic wounds remains one of the most significant growing unmet medical needs in the world! Therefore, it is particularly exciting for us to shed light on a treatment method that can potentially solve this big medical problem and improve standards of living for millions of patients.
Gap junctions targeted therapy
Gap junctions are key mediators of cell-cell communication. It was reported that one of these gap junctions proteins- Connexin 43 (Cnx43) is expressed at significantly higher levels at chronic wound edges. (1) This discovery led to the development of one of the most promising treatments of wound healing, which is a gel that promotes down-regulation of Cnx43 expression at the wound edges.(2) Application of this gel dramatically reduces the redness and inflammation within a few hours after the application.
Numerous studies have demonstrated the effectiveness of this approach in treating chronic wounds such as diabetic foot ulcers as well as severe corneal (the transparent portion of the eye that covers its front portion) injuries caused by chemical and thermal burns which did not respond to any conventional types of treatment. (3, 4) We decided not to include pictures of the wounds to this article as they might be too graphic, but the effect of the Connexin 43 antagonist gel show fascinating results. For example, a patient with a severe eye acidic burn managed to save his vision and another patient escaped the need for the below the knee amputation due to the failure of the wound healing after the first amputation.
There are other treatment methods that are available such as oxygen delivery to the wound site, application of antimicrobial agents and growth factors, which could be useful as an additional treatment to Connexin 43 therapy, but on its own all of them are far less effective.
1)White TW, Bruzzone R. Multiple connexin proteins in single intercellular channels: connexin
compatibility and functional consequences. Journal of bioenergetics and biomembranes. 1996 Aug
2) Qiu C, Coutinho P, Frank S, Franke S, Law LY, Martin P, Green CR, Becker DL. Targeting
connexin43 expression accelerates the rate of wound repair. Current Biology. 2003 Sep
3)Wang CM, Lincoln J, Cook JE, Becker DL. Abnormal connexin expression underlies delayed wound
healing in diabetic skin. Diabetes. 2007 Nov 1;56(11):2809-17.
4)Ormonde S, Chou CY, Goold L, Petsoglou C, Al-Taie R, Sherwin T, McGhee CN, Green CR.
Regulation of connexin43 gap junction protein triggers vascular recovery and healing in human ocular persistent epithelial defect wounds. The Journal of membrane biology. 2012 Jul 1;245(7):381-8.