Ubiquitin for the Treatment of Inflammation in Surgery and in Trauma
Matthias Majetschak and Kenneth Proctor
Problem
Trauma and sepsis are difficult to treat and the current approaches have a variety of untoward side effects. In many cases of disease progression and inflammation, fluid shift is often the cause of morbidity and mortality. Ideally, a compound which is naturally released in response to trauma could be harnessed for its anti-inflammatory qualities.
Solution
Extracellular ubiquitin released after trauma has cytokine-like properties and has anti-inflammatory actions. It is effective in stabilizing fluids regardless of the cause of inflammation. In a swine model for endotoxic shock, intravenous doses of ubiquitin reduced:
1) almost all classical symptoms of inflammation,
2) mortality to zero in the treated group from 50% in the untreated controls, and
3) fluid requirements, indicating a reduction in capillary leakage. Doses of ubiquitin also did not confer any detectable side effects in normal healthy animals. Furthermore, in a swine model for severe brain injuries, effects of ubiquitin dramatically reduced:
1) fluid shifts into the tissue,
2) fluid requirements and
3) intracranial pressure. Doses of ubiquitin also prevented lung malfunction.
Competitive Advantage
Ubiquitin does not produce any detectable, adverse side effects, and is extremely effective in reducing inflammation, regardless of the cause.
Applications
Ubiquitin may be administered after brain injuries in particular and as a treatment for shock, trauma, burns, infections/sepsis and transplant rejection. Ubiquitin may also be administered as a pretreatment in patients undergoing major surgical procedures.
Patent Status
United States Divisional Patent Appln No. US20070207162 A1 entitled "UBIQUITIN AND UBIQUITIN RELATED MOLECULES FOR TREATMENT AND PREVENTION OF HARMFUL ACTIVATION OF THE IMMUNE SYSTEM" was published on September 6, 2007.
Licensing Opportunity
We are seeking a commercialization partnership for novel, safe and effective anti-inflammation therapy.
About the Inventors
Dr. Matthias Majetschak, M.D., Ph.D., was a Research Associate Professor in the DeWitt Daughtry Family Department of Surgery, Division of Trauma and Surgical Critical Care. He is currently Assistant Professor, Department of Surgery and The Burn & Shock Trauma Institute, Loyola University Medical Center, Chicago.
Dr. Kenneth G. Proctor, Ph.D, is a Professor of Surgery in the DeWitt Daughtry Family Department of Surgery, Division of Trauma and Surgical Critical Care. He is also a Professor of Anesthesiology and Biomedical Engineering and Scientific Director of Research.
Selected References
Earle SA, El-Haddad, A, Patel MB, Ruiz P, Pham SM, Majetschak M. Prolongation of skin graft survival by exogenous ubiquitin. Transplantation. 2006, 82:1544-1546.
Patel MB, Feinstein AJ, Saenz AD, Majetschak M, Proctor KG: Pre-hospital HBOC-201 After Traumatic Brain Injury and Hemorrhagic Shock in Swine. J Trauma. 2006, 61(1):46-56.
Earle SA, Proctor KG, Patel MB, Majetschak M. Ubiquitin reduces fluid shifts after traumatic brain injury. Surgery. 2005, 138:431-438.
Majetschak M, King DR, Krehmeier U, Busby LT, Thome C, Vajkoczy S, Proctor KG. Ubiquitin immunoreactivity in cerebrospinal fluid after traumatic brain injury: clinical and experimental findings. Crit Care Med. 2005, Jul;33(7):1589-94.
Majetschak M, Cohn SM, Obertacke U, Proctor KG. Therapeutic potential of exogenous ubiquitin during resuscitation from severe trauma. J. Trauma. 2004, 56(5): 991-1000.
