Chattopadhyay, Munmun , PhD
The role of neuroinflammation in the pathogenesis of pain in diabetic neuropathy
General Research Subject: Both Type 1 And Type 2 Diabetes
Focus: Complications, Complications\Nephropathy
Type of Grant: Basic Science
Project Start Date: July 1, 2012
Project End Date: June 30, 2015
Painful diabetic neuropathy (PDN) is a long-term complication of both Type 1 and Type 2 diabetes that interferes with the quality of life. Unfortunately, available medical treatment is relatively ineffective. A number of studies have shown the contribution of inflammatory cytokines, a compound that is made by the body as part of its immune function under stressful condition, as a cause of pain. In this study we will find out whether this notion is similar or different in Type 1 and Type 2 diabetes, establish the role of inflammation with development of pain, and determine whether interruption of this process by gene therapy would alleviate the pain. These studies will help define the mechanisms that are responsible for pain in diabetic neuropathy and establish novel treatments for this relatively treatment resistant condition.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
My research area is diabetic complications. Pain is one of the most common debilitating long-term complications of Type 1 and Type 2 diabetes. Twenty to twenty-five percent of patients with diabetic neuropathy suffer from pain caused by the damage to the peripheral nerves. Traditional pharmacological agents are not of great benefit and interferes the quality of life. Therefore, new methods to treat painful neuropathy need to be developed. These studies will test a novel therapeutic approach to treat painful diabetic neuropathy (PDN) by using gene transfer. We will be studying the implication of inflammatory cytokines in the development and pathogenesis of pain in diabetes. To interrupt the inflammatory cascade in the peripheral nervous system, we will use genetically modified herpes simplex virus (HSV) to express anti-inflammatory peptide, tumor necrosis alpha soluble receptor (sTNFR), or interleukin-10 (IL10), which will reduce the pain associated with inflammatory changes in diabetic neuropathy. The studies of this project are of direct relevance for understanding the pathogenesis of pain in diabetic neuropathy and may provide a novel approach to treat what is currently a relatively treatment resistant complication of diabetes.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
Peripheral neuropathy (death and malfunction of the nerves in the legs and arms) is the most common side effect of diabetes which is not very easy to treat. In the United States, there are more than 14 million people who are affected by this complication. We will make a rat model with diabetic painful neuropathy and test HSV vector that has been genetically altered to express proteins. The vector will be delivered through skin injection, which we believe will reduce pain in diabetic animals. We will perform a number of behavioral tests to evaluate the extent of pain in the rats which will provide information about how well our treatment works. We will then modify this particular vector to treat patients with painful neuropathy and find the right dose of the viral vector in Phase 1 and Phase 2 clinical trials. Successful completion of these studies may lead to more effective treatment for painful neuropathy in diabetes.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
The global diabetes burden is predicted to rise to 380 million by 2025 and would present itself as a major health challenge. Both T1D and T2D (Type 1 and 2 diabetes) increase the risk of developing micro- and macro-vascular complications leading to neurological dysfunction in diabetic patients, with a devastating impact on quality of life of the patients and a challenge to health services worldwide. With the ultimate aim of developing a therapy that will effectively treat the patients with painful diabetic neuropathy, my research is focused on establishing the role of increased proinflammatory cytokines in the pathogenesis of pain in Type 1 and Type 2 model of diabetes, to examine whether by interrupting the neuroinflammatory cascade using gene transfer with replication defective herpes simplex virus (HSV) vector expressing anti-inflammatory agent would decrease the pain-related behaviors, and studying the role of the altered inflammatory mediators on the changes in ion channels in the development of pain in diabetes. These studies will help define the potential role of proinflammatory cytokines in painful neuropathy and will provide a novel treatment strategy for what is now a relatively treatment resistant condition.
In what direction do you see the future of diabetes research going?
The treatment of diabetes and its complications remains a major challenge due to its high prevalence, health and socioeconomic impact. Although there's a great deal of research under way for a better diabetes treatment or cure, diabetic complication research still remains under-recognized despite its prevalence and relevant impact on quality of life. The necessity for research on diabetes may increase as the numbers of diabetic population continue to rise. I anticipate a time when diabetic complications will be prevented with one or combination of drugs, and diabetes will be cured by using new treatment strategies like gene therapy and stem cell therapy.
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