Antilysophosphatidic Acid Antibodies in the Treatment of Post-TBI Neuropathic Pain
Abstract
The prevalence of concussions in Warfighters returning from Iraq or Afghanistan has been estimated at approximately 19.6%, and the prevalence of post-traumatic headaches, defined as headaches beginning within 1 week after a concussion, was 37% in Soldiers, with 27% diagnosed with chronic daily headache and central traumatic brain injury (TBI)-induced neuropathic pain. Chronic pain, including chronic headaches, can be extremely debilitating, leading to greatly reduced quality of life, including difficulties in maintaining employment or meeting educational goals. Particularly in the context of Veterans, chronic pain can also contribute to psychological dysfunctions, where, for example, chronic pain is frequently comorbid with post-traumatic stress disorder. Current therapies, such as non-steroidal anti-inflammatory drugs (NSAID), opiates, anti-epileptics, and triptans can help some patients, but are far from universally effective and have, in some cases, substantial side-effect, and in the case of the opiates, abuse potential. Thus, there is an acute need for improved strategies to prevent the development or treat existing chronic pain in Warfighters and Veterans suffering from head trauma. Lpath, Inc. has developed a novel anti-LPA (lysophosphatidic acid) antibody therapeutic that holds great promise as a treatment for neuropathic pain in TBI patients with the potential added benefit of providing neuroprotection by reducing the primary brain injury itself. We have demonstrated in preliminary experiments, significant improvements in neuropathic pain outcomes after TBI. These data, taken with our previous data demonstrating neuroprotection after TBI strongly suggest that LPA dysregulation/upregulation is causal to injury progression and to the outcome of neuropathic pain following TBI, and that interventions to reduce LPA will have a significant impact in TBI induced pain as well as cognitive dysfunction. Accordingly, the proposed study is aimed to identify the role of LPA in the process of central fluid percussion (cFP) model of TBI pain and other behaviors and to further develop our anti-LPA antibody therapeutic in ameliorating the chronic effects of TBI with a focus on neuropathic pain. Understanding the role of LPA in TBI-induced central neuropathic pain and the development of effective therapy will be beneficial for affected Service members as well as civilian population for protection and to attenuate the chronic effects of diffuse head injury. Lpath has filed an Investigational New Drug Application (IND) with the Food and Drug Administration after completing further efficacy, safety, ADME [absorption, distribution, metabolism, and excretion], and toxicology studies. Lpath is studying the safety and efficacy of Lpathomab in neuropathic pain patients. By the end of the project period, Lpath will have animal efficacy data in TBI pain that will allow Lpath to modify its IND and study TBI pain patients in a Phase 1b/2a safety and efficacy trial.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1610098
Entities
People
- Roger Sabbadini
Organizations
- United States Army