Novel Anti-LPA Antibody for the Treatment of Traumatic Brain Injury
Award last edited on: 11/4/14

Sponsored Program
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Principal Investigator
Roger A Sabbadini

Company Information

Lpath Inc (AKA: Medlyte Inc~Lpath Therapeutics Inc)

4025 Sorrento Valley Boulevard
San Diego, CA 92121
   (858) 678-0800
Location: Single
Congr. District: 51
County: San Diego

Phase I

Contract Number: 1R44NS087641-01
Start Date: 5/1/14    Completed: 11/30/14
Phase I year
Phase I Amount
There are 1.7 million cases of Traumatic Brain Injury (TBI) per year in the U.S. with 125,000 having permanent disability. To date, there are no FDA-approved drugs for treating TBI. Lpath, Inc. has developed a novel anti-LPA (lysophosphatidic acid) antibody therapeutic that holds great promise as a treatment for TBI patients. LPA is an endogenous bioactive lipid that has been very well studied. The literature clearly shows that LPA (i) has widespread developmental, physiological and pathological actions, (ii) controls events within the nervous, reproductive, gastrointestinal, and vascular systems, and (iii) plays a prominent role in cancer, mammalian embryogenesis and stem-cell biology. In the CNS, LPA is synthesized by astrocytes, choroid plexus epithelial cells and inflammatory cells and is released upon cell activation. Its concentration within the brain increases during inflammation, clotting and neurotrauma, at which time it likely potentiates its known roles in astrocyte proliferation, neuronal death, axonal injury and microglial activation. Our preliminary and published data indicate a specific upregulation of LPA receptors following injury to the adult mouse CNS, where LPA has been shown to induce neuronal apoptosis and to inhibit neural stem/progenitor cell differentiation along a neuronal lineage. In addition, LPA receptors are similarly increased after human brain injury. Moreover, LPA levels are upregulated in the CSF of TBI patients, suggesting LPA plays a role in the pathology of TBI. Lpath's anti-LPA antibody (Lpathomab) is highly specific in selectively neutralizing LPA and thereby lowering LPA's effective levels in the extracellular space. When administered systemically (single dose post-injury) in mouse and rat models of TBI and spinal cord injury (SCI), Lpathomab provides ~50% neuroprotection while also reducing reactive gliosis, promoting axonal sprouting, protection against axonal injury, and increasing synaptic regeneration by promoting a neuronal, rather than glial, fate of neural stem/precursor cells. Moreover, we have demonstrated significant improvements in neurobehavioral outcomes in both TBI and SCI neurotrauma studies with functional endpoints. These data strongly suggest that LPA dysregulation/upregulation is causal to injury progression and to the outcome of neural damage/repair following TBI; and that interventions to reduce LPA will have a significant impact in several neuropathophysiologies, including TBI. We propose that Lpathomab could satisfy a critical unmet need by limiting the initial neuronal damage and subsequently stimulating regenerative processes to optimize long-term functional outcomes after neurotrauma. The overall goal of the proposed work is to submit an Investigational New Drug Application (IND) with FDA after completing further efficacy, safety, ADME and toxicology studies that are described. By the end of the project period, Lpath will be positioned for testing Lpathomab in healthy volunteers in a Phase 1 safety trial, followed by a Phase 1b/2a safety and efficacy trial in a well-defined population of TBI patients.

Thesaurus Terms:
Accidents;Adme Study;Adult;Afghanistan;Animal Model;Antibodies;Area;Astrocytes;Axonal Sprouting;Behavioral;Binding (Molecular Function);Biological Assay;Blocking Antibodies;Blood - Brain Barrier Anatomy;Brain;Brain Injuries;Cause Of Death;Cell Differentiation Process;Cells;Cessation Of Life;Clinical;Coagulation Process;Controlled Cortical Impact;Data;Development;Disability;Dose;Drug Targeting;Efficacy Trial;Embryonic Development;Epithelial Cells;Event;Extracellular Space;Falls;Fda Approved;Functional Disorder;Functional Outcomes;G-Protein-Coupled Receptors;Gastrointestinal System;Gliosis;Goals;Head;Healthy Volunteer;Home Environment;Human;Improved;In Vitro;In Vivo;Inflammation;Inflammatory;Inflammatory Response;Inhibitor/Antagonist;Injury;Intervention;Investigational New Drug Application;Iraq;Ligands;Lipids;Literature;Lysophosphatidic Acid;Lysophosphatidic Acid Receptors;Lysophospholipids;Malignant Neoplasms;Mediator Of Activation Protein;Military Personnel;Modeling;Monoclonal Antibodies;Mouse Model;Mus;Natural Regeneration;Necrosis;Nervous System Structure;Neurobehavioral;Neuron Apoptosis;Neuron Loss;Neuronal Differentiation;Neurons;Neuroprotection;Novel;Outcome;Pathology;Patients;Penetrating Head Injuries;Pharmaceutical Preparations;Pharmacology And Toxicology;Phase;Physiological;Plasma;Play;Population;Positioning Attribute;Precursor Cell;Process;Public Health Relevance;Publishing;Rattus;Regenerative;Rehabilitation Therapy;Relating To Nervous System;Repaired;Reproductive System;Research;Response;Response To Injury;Role;Safety;Safety Study;Signal Transduction;Source;Sphingosine 1-Phosphate;Spinal Cord Injury;Stem;Stem Cell Biology;Stem Cells;Structure Of Choroid Plexus;Synapses;Testing;Therapeutic Antibodies;Time;Tissues;Tool;Toxicology;Trauma;Traumatic Brain Injury;Up-Regulation (Physiology);Vascular System;Veterans;Work;

Phase II

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Start Date: 00/00/00    Completed: 00/00/00
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