Lpath and Walter Reed Army Institute for Research begin efficacy study using Lpathomab in traumatic brain injury models


Lpath and scientists from the Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research (WRAIR), USA, have initiated a study on the use of Lpathomab, an antibody to lysophosphatidic acid (LPA), in the treatment of brain injury induced by blast overpressure.

The investigators at WRAIR are Joseph Long, a US Army civilian and chief, Blast Induced Neurotrauma Branch Center for Military Psychiatry and Neuroscience at WRAIR, and Peetthambaran Arun, from Clinical RM (both USA).

According to a press release, the use of improvised explosive devices and hand-held grenades in recent wars has increased the incidence of blast traumatic brain injury, a major cause of disability among service members. The prevalence of concussions in soldiers returning from Iraq or Afghanistan has been estimated at approximately 19.6%, and accounts for 150,000 casualties. There are currently no US Food and Drug Administration-approved drug treatments for any form of traumatic brain injury, it states in the release.

Lpath and collaborators recently published work showing that Lpathomab reverses much of the damage caused by trauma to the nervous system in a controlled cortical-impact model of traumatic brain injury in mice (Journal of Neuroinflammation, volume 11(1):37). The Lpath-WRAIR collaboration is expected to extend those studies to determine if Lpathomab can be used to reduce the size of a blast brain injury and to improve functional behavioural outcomes in experimental animal models.

Lpath is currently conducting IND-enabling studies for Lpathomab and intends to enter phase I clinical trials in early 2015 for neuropathic pain and neurotrauma.


*Figure: anti-LPA mAb significantly reduces lesion volume and diffusion following traumatic brain injury:

A, B: Representative images of mouse brains two days following traumatic brain injury, isotype control (A) or B3 (B) received 30 minutes post injury showing the extent of haemorrhage.
C, D: Representative quantification of injury volume two days following traumatic brain injury after Nissl 2 staining, with treatment received one hour pre-injury (C) or 30 minutes post-injury (D); means±standard error of the mean (SEM), n>7 animals; p<0.05, p<0.01 by two-tailed t-test.
E: Representative T2 maps of mouse brain one and seven days following traumatic brain injury in control animals (isotype) or animals treated with B3 (antibody), both given at 25 mg/kg, 30 minutes post injury, by tail-vein injection.

F: Representative mean diffusivity map following the same protocol.

G: Quantification of infarct volume using T2 maps.

H: Mean diffusivity maps in isotype controls (traumatic brain injury) and B3-treated animals (trumatic brain injury+LPA antibody). Data aremeans±SEM, n=8 animals; p<0.05 by t-test.