A therapy that limits the damage that ensues following a spinal cord injury (SCI) at its earliest stages will address a clearly unmet medical need in both civilian and military populations. Preservation of as much neurological function as possible will provide the best chance of achieving a higher quality of life for those who have suffered a SCI. Our anti-inflammatory therapy has been designed to target the very early acute stage of inflammation that arises following SCI. This therapy has the potential to address the critical need for preservation of tissue and neurological function. SCI is most frequent in young adults at a time when they are most active in society and at or approaching their economically most productive time of life. The impact of SCI and CNS trauma on civilians and military service members and their families is often psychologically and financially devastating to those affected. The long-term care of individuals with SCI is a significant long-term drain on health care dollars.

Our preclinical animal studies clearly demonstrate that our antibody targets a protein, known as CD11d, on the surface of inflammatory cells that circulates in the blood. CD11d is required by the inflammatory white blood cells to leave the blood stream and enter a site of tissue injury including the injured spinal cord. This protein is also required to retain the white blood cells at the injury site. When our antibody binds to the protein, the inflammatory white blood cells are blocked from leaving the blood vessel and entering the site of SCI. Furthermore, any white blood cells that do enter can no longer adhere and be retained at the injury site so they either die or leave. By blocking the entry and retention of these white blood cells at the site of injury we successfully reduce inflammation and preserve neurological function. In our preclinical models our antibody-mediated anti-inflammatory therapy leads to improved walking, improved cardiovascular function, and reduced chronic pain. We have expanded our studies to traumatic brain injury and our initial results suggest that the anti-inflammatory treatment to block the function of CD11d may also be protective for this indication. The antibody we have been testing binds to human CD11d and can be shown attached to CD11d on the surface of human white blood cells of able-bodied individuals and patients with acute SCI. Our treatment strategy is to start our antibody treatment within hours of the SCI by injecting it into the blood stream to block directly the entry of inflammatory white blood cells into the injury site. We do not have to inject the antibody into the injured spinal cord and risk further injury to the cord. Our aim is not to destroy the white blood cells that express the CD11d protein but to temporarily block their function for a short period of time. This allows the immune system to continue to protect against infection.

Our multidisciplinary research team brings together basic scientists and clinician scientists with a combined expertise in neurotrauma, combat casualty care, neuroimmunology, and molecular and cellular neurobiology and immunotherapy. One of our clinician scientists is a spine surgeon who treats patients with acute SCI and the other is from the U.S. Navy and has expertise in deep dive decompression sickness-induced spinal cord injury.

To move the anti-CD11d antibody therapy to a clinical trial for human SCI, we have entered into an important agreement with Eli Lilly and Co. to have our antibody converted into an optimized form suitable for therapeutic use in humans. However, we still need funds to advance our project toward a clinical trial. This is a critical step forward and Eli Lilly has committed significant resources and funds to this project. Among the goals that must be accomplished before testing out treatment in a clinical trial is possible, three are paramount. First, we must develop tests that will allow us to detect and track the anti-CD11d antibody in humans and to determine that it is functioning properly. Second, we must determine that the engineered antibody retains its function to improve neurological recovery from SCI in rodent models of SCI. Third, we need to develop large animal models of SCI that more accurately reflect the pathology of human SCI in terms of the types of injuries that civilian and military service members incur. The funds provided by this U.S. Department of Defense grant to support clinical translational of our therapy for SCI will be crucial in allowing us to complete the critical steps necessary to advance our optimized anti-inflammatory therapy to a human clinical trial.