Neurogenic Stroma Reprogramming to Rescue Diabetic Neuropathy
Abstract
This proposal addresses the FY20 Peer Reviewed Medical Research Program Topic Area: Diabetes and the specific area of encouragement, “Research on interventions to prevent or treat diabetes complications, including diabetic neuropathy.” Problem: According to estimates from the Centers for Disease Control and Prevention, 30.2 million people, or 9.4% of the US population, have diabetes. People who are diabetic, prediabetic, or obese are at high risk of developing diabetic neuropathy, which is chronic nerve damage that often affects the feet and hands. Neurosensory damage is most commonly seen in diabetic conditions that can cause numbness or pain in the toes, feet, legs, hands, and arms. This is an early sign of a much larger problem that may involve the development of foot ulcers followed by amputation and early loss of life. It is estimated that 30% to 50% of diabetic patients eventually develop diabetic symptomatic peripheral neuropathy (DPN). DPN accounts for more hospitalizations than all other diabetic complications combined and is the major cause of amputations in the United States, accounting for 50% to 70% of all non-traumatic amputations. Reportedly, 8.7% of women and 10% of men who served the US military during 2013-2014 were diagnosed with diabetes. For military personnel, diabetes is a chronic illness that presents many barriers to readiness in the active duty force. In addition, mismanagement of diabetes and the resulting complications of this condition can lead to the loss of mobility and lower limb function, impacting our Veterans later in life and, as a result, the Veterans Health Administration. Innovation: Scientific studies have shown that tissue of the adult body can be genetically reprogrammed to alter functionality for therapeutic purposes using a platform technology called Tissue Nanotransfection Technology (TNT). TNT is a novel nanoelectroporation technology for gene delivery to the affected part of the body. Delivery of appropriate genes can reprogram tissue function in vivo. For example, intact live skin cells have been successfully converted to functioning blood vessels that have successfully rescued traumatized limbs. Similarly, cells of the intact skin have been reprogrammed to generate functional nerve cells. Interestingly, in these studies, as skin cells progressed towards acquiring nerve cell properties following TNT intervention, other skin cells in the same microenvironment display the ability of producing copious amounts of factors that are known to develop repair and regenerate nerve cells. This proposal evaluates the TNT approach to rescue pre-existing nerve fiber circuits in diabetes-affected skin that are at risk of perishing because of long-term diabetes. In its final form, the device will look like a hand-held stapler equipped with microfluidics and power supply. The injectable (ABM) will be packaged in disposable cartridges that will eject from the “stapler” after single use. Ultimate Applicability and Impact of Research: The proposed line of investigation seeks to develop a novel treatment paradigm aimed at rescuing neurosensory damage in diabetes. The treatment can be applied in a low-resourced care setting at minimal cost in a matter of few minutes. The proposed intervention does not require any hospital or laboratory infrastructure for delivery, neither does it need skilled individuals, making the scope of impact broad. Any healthcare provider may be trained in administering TNT within 2 hours, making it suitable for application in far-forward settings. Once efficacy is established in DPN, this approach may also be evaluated for other applications, for example, to regenerate neuromuscular junction in a situation where significant loss of skeletal muscle has been caused by trauma.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110047
Entities
People
- Savita Khanna
Organizations
- Indiana University
- United States Army