Developing Pro-NP for Acute Spinal Cord Injury
Abstract
Spinal cord injury (SCI) is devastating to the lives of all victims and their families. Each year in the United States over 12,000 people sustain an acute SCI that changes their lives forever because there is no effective treatment to prevent paralysis or to minimize the effect of injury. According to the 2013 report from the Christopher & Dana Reeve Foundation, more than a million people in the United States, ~0.4% of the population, are living with paralysis due to SCI, and it is estimated to cost $40.5 billion annually to the healthcare industry. In addition to civilian population, there is significantly higher rate of SCI (~5% to 15%) among all other combat-related injuries. Disability due to SCI is a major global issue, affecting mainly younger populations. The goal of this grant is to minimize the effect of initial injury on further protracted damage and promote regeneration. ProTransit Nanotherapy has exclusive rights to develop and market special nanoparticles that can help reduce the impact of a SCI. Nanoparticles are extremely small particles (in nanometer range, 1 nm = one billionth of a meter) that can be loaded with a variety of medicines. ProTransit Nanotherapy calls their special nanoparticles, Pro-NP. Pro-NP stabilizes the drug, particularly those that are not stable in the body and are eliminated quickly, delivers it to the spinal column, more specifically to the injured site, and then gradually releases the drug over the next several weeks. Pro-NP is very gentle to the body since it gradually dissolves, is made from Food and Drug Administration (FDA)-approved components, and is then metabolized and eliminated by the body over a period of time. The special cargo Pro-NP carrier for the treatment of SCI contains combination of antioxidant enzymes, superoxide dismutase and catalase. These enzymes play a protective role from very damaging molecules called free radicals. Free radicals are a natural by-product of metabolism and are generally controlled by these enzymes in the body. Following SCI, the level of free radicals goes way up, whereas the levels of antioxidant enzymes go down, causing an imbalance, resulting in oxidative stress. This oxidative stress at the impact site triggers a cascade of degenerative events, spreading along the spinal cord with time, thus expanding the injury response. Hence, patients with SCI develop additional disability with time such as respiratory failure, bladder dysfunction, muscular atrophy, etc. Neuronal tissue is particularly more susceptible to damage due to free radicals because of sensitivity of their cell membrane lipid composition. The damage results in scaring of the spinal tissue, preventing neuronal connectivity, resulting in permanent disability. Our goal is to neutralize free radicals effectively and hence their damaging effects by delivery of Pro-NP at the impact site. These enzymes as such are not effective because of their instability and rapid clearance from the body (half-life = 8-11 minutes). Our Pro-NP formulation stabilizes these enzymes and prolongs their effect at the impact site, thus preventing the cascades of degenerative events that occur following SCI. Further, it creates conducive conditions for neuronal repair to occur by natural mechanism of the body, thus regaining locomotive function. The Principal Investigator of this proposal has shown that intravenous injection of Pro-NP a few hours after SCI results in significant physiological improvement compared with untreated animals. In fact, treated animals were able to walk again while control animals showed only modest improvement and remained generally paralyzed for the course of the study. The proposed grant will allow ProTransit Spinal Nanotherapy to expand these preliminary studies to a different laboratory (University of British Columbia) and determine efficacy in a different animal model of SCI. The scale-up and finalization of pilot production of Pro-NP will be car
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610786
Entities
People
- Vinod Labhasetwar
Organizations
- Cleveland Clinic
- United States Army