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Press Release: Swedish researchers’ discovery promises unique medicine for treatment of chronic and diabetic wounds
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A unique new medicine that can start and accelerate healing of diabetic and other chronic wounds is being developed at Umeå University in Sweden. After several years of successful experimental research, it is now ready for clinical testing.
Behind this new medicine is a group of researchers at the Department of Medical Chemistry and Biophysics who have made the unique finding that the protein plasminogen is a key-regulator that initiates and accelerates wound healing by triggering the inflammatory reaction. Their discovery is now being published in the highly ranked journal Blood.
“Today we have the knowledge needed to develop a medicine,” says Professor Tor Ny, one of the authors of the article. “The bulk of the preclinical research has been completed, and we have had meetings with the Medical Product Agency to discuss a program for clinical testing.”
Plasminogen is a well-known plasma protein that is produced in the liver and found in all bodily fluids. The Umeå researchers have now re-assessed its role and managed to show that the concentration of plasminogen increases dramatically in and around wounds, which is an important signal to start the inflammatory reaction required for healing. In diabetic wounds the level of plasminogen does not increase in the same way, and this seems to be the reason why these wounds do not heal. In diabetic mice and rats the researchers were able to show that the healing process starts immediately when plasminogen is injected around the wound, which then heals fully.
A cell line for producing plasminogen on a larger scale has also been developed, and the goal is to start clinical testing as soon as funding can be arranged. The researchers have high hopes, as plasminogen is an endogenous protein that can be assumed not to produce side effects.
The need for a biologics for treating chronic wounds is urgent. Diabetic wounds that do not heal are the most severe type of chronic wounds, affecting millions of people annually. Many of the roughly 350 million diabetes patients in the world develop foot ulcers, and in 10-15 million cases this ultimately leads to amputation. Today’s treatment of diabetic wounds consists primarily of traditional wound care, with compresses and bandages; there is no effective medication.
The Umeå researchers are initially concentrating on diabetic wounds, but plasminogen also has great potential for working on other types of wounds. This includes tympanic membrane perforations and periodontitis. Being a pro-inflammatory activator, plasminogen has moreover been shown to be effective in combating antibiotic-resistant bacteria (MRSA).
Plasminogen is a key pro-inflammatory regulator that accelerates the healing of acute and diabetic wounds.
Y. Shen, Y. Guo, P. Mikus, R. Sulniute, M. Wilczynska, T. Ny, J. Li. Blood, 2012;
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Despite decades of research on wound healing, effective biologic agents for the treatment of chronic wounds, especially diabetic wounds, are still lacking. In this study, we report that the inert plasma protein plasminogen (plg) acts as a key regulatory molecule that potentiates wound healing in mice. Early in the healing process, plg bound to inflammatory cells is transported to the wound area, where the level of plg is locally increased. This leads to induction of cytokines and intracellular signaling events and to a potentiation of the early inflammatory response. Systemic administration of additional plg not only accelerates the healing of acute burn wounds in wild-type mice but also improves the healing of chronic diabetic wounds in a mouse model of diabetes. Our results suggest that administration of plg may be a novel therapeutic strategy to treat many different types of wounds, especially those that are chronic, such as diabetic wounds.
Press Release: Discovery of a novel medicine for the treatment of chronic wounds
Plasminogen seen to help the healing process
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Every 20 seconds, a limb is lost as a consequence of diabetic foot ulcer that does not heal. To date, medical solutions that can change this situation are very limited. In his doctoral thesis Yue Shen from the Industrial Doctoral School and the Department of Medical Biochemistry and Biophysics at Umeå University presented a novel medicine for chronic wound treatment that may completely change the lives of millions of patients.
Diabetic wounds are the most severe type of chronic wounds that largely impair the quality of life in patients and inflict an enormous burden on the healthcare system. World-wide, there are more than 350 million diabetic patients and about 20% of them develop diabetic foot ulcers that often do not heal, which eventually lead to amputation. Chronic eardrum perforations are another type of chronic wounds. Today the only existing treatment of chronic eardrum perforations is through surgery.
In his thesis, Yue Shen demonstrates that plasminogen, a well-know plasma protein, acts as a key regulatory molecule of inflammation that can be used to treat different types of chronic wounds including diabetic wounds and chronic eardrum perforations. Yue Shen demonstrates that the level of plasminogen dramatically increases in and around wounds, which leads to an enhanced inflammation that is required for healing. In diabetic wounds that do not heal, the level of plasminogen does not increase and the inflammatory response is suppressed. When plasminogen is injected around diabetic wounds, the healing process starts and the wounds eventually heal fully. In chronic eardrum perforations, local injection and topical application of plasminogen also stimulates the healing and leads to complete healing.
Based on these studies, a controlled clinical study using human plasminogen to treat chronic wounds in humans is now planned. The ultimate goal is to develop plasminogen to a medicine for the treatment of various chronic wounds.
The findings in Yue Shen's thesis not only reshape our molecular understanding of the role of plasminogen during wound healing process, but also bring the hope to millions of desperate patients who suffered from chronic wounds.
In the treatment of diabetic ulcers is a new drug, or any therapy involved in directly healing a diabetic ulcer really as important as the overall health status of the patient, or the overall condition of the affected limb?
Is it even as important as good load reduction?
Press Release: Swedish researchers’ discovery promises unique medicine for treatment of chronic and diabetic wounds
I will be pleasantly surprised if plasminogen will help wounds heal. Most wounds do not heal because there is not enough nutrients, including oxygen to allow cells to grow. If circulation isn't increased how will the plasminogen help in those patients who have poor circulation?