Eos Neuroscience, Inc., in collaboration with the company's academic partners, is developing a novel technology combining gene therapeutics and optical neuromodulation techniques to enable a potential therapy for neuropathic pain. It is the hope of our company that this technology will be widely applicable and available to individuals in the United States and worldwide that suffer from debilitating chronic pain. In brief, Eos Neuroscience, Inc. is creating a technology that will restore inhibition to hyperactive neurons in the dorsal root ganglion (DRG) with fiber optic illumination. To this end, we are developing a targeted delivery mechanism using an adeno-associated virus (AAV) that is proven effective at delivering genes into DRG. We will use this mechanism to target a photosensitive inhibitory proton pump, into the nociceptive DRG neurons and study the immunohistochemical localization of our transgene and physiology of these transduced DRG. The goal of this Phase I project is to characterize the targeting efficiency and specificity with which we can deliver our transgene to nociceptive DRG neurons using ubiquitous and cell specific promoters. We will then perform electrophysiology to characterize the light driven inhibitory responses in transduced DRG neurons to determine the efficacy with which we can silence spontaneous hyperactivity. We have started this testing in rats and will continue to evaluate both vector targeting and physiological measures. Accordingly, we propose the following specific aims for our SBIR Phase I project: 1) Design and construct AAV vectors using well-characterized promoters, for specific expression of an optical silencer in nociceptive neurons of the DRG, 2) Deliver AAV vectors via intrathecal injection to rodent DRG and evaluate targeting specificity and toxicity via Immunohistochemistry, and 3) Characterize the optical silencing capability of these AAV vectors in DRG using cell attached and whole cell intracellular recording. We are very enthusiastic that results obtained from this Phase I study will enable us to submit a Phase II with the eventual goal of a clinical therapeutic product.
Public Health Relevance: Pain is a major health problem, with 290 million people suffering worldwide and 86 million in the US. Current therapeutic approaches (e.g., pharmacological, surgical, electrical stimulation and physical rehabilitation therapy) generally fail to target pain pathways selectively, resulting in undesired side effects that can significantly impair physical and mental ability and may include central nervous system depression, cognitive dysfunction, blockade of motor neurons, and weakness. To this end, Eos Neuroscience, Inc. and academic partners will establish a gene therapy based technology that can be applied broadly using a light sensitive protein to silence pain sensation directly in sensory neurons of patients suffering from chronic pain.
Thesaurus Terms: Aav Vector;Acute Pain;Adeno-Associated Viruses;Adverse Effects;Afferent Neurons;Allergy;Area;Behavioral;Bipolar Neuron;Brain Region;Cmv;Catheters;Cations;Cell/Tissue, Immunohistochemistry;Cells;Central Nervous System;Chloride;Chloride Ion;Chlorides;Cl- Element;Clinical;Clinical Treatment;Cognitive Disturbance;Cognitive Impairment;Cognitive Decline;Cognitive Function Abnormal;Collaborations;Common Rat Strains;Complementary Dna;Cytomegalovirus;Dna Molecular Biology;Dna, Complementary;Dependovirus;Depression;Development;Disease;Disorder;Disturbance In Cognition;Dorsal Horn Of The Spinal Cord;Dorsal Root Ganglia;Electric Stimulation;Electrical Stimulation;Electrophysiology;Electrophysiology (Science);Esthesia;Euler-Gaddum Substance P;Flr;Failure (Biologic Function);Fiber Optics;Foundations;Ganglia, Spinal;Gene Transfer;Gene Transfer Clinical;Gene Transfer Procedure;Gene-Tx;Genes;Genetic;Genetic Intervention;Glia;Glial Cells;Goals;H(+) Pump;Hcmv;Halorhodopsin Chromoprotein;Halorhodopsins;Health;Hyperactive Behavior;Hyperactivity;Hyperactivity, Motor;Hyperkinesia;Hyperkinesis;Hyperkinetic Movements;Hypersensitivity;Ihc;Illumination;Image;Immunohistochemistry;Immunohistochemistry Staining Method;Impaired Cognition;In Vitro;Individual;Injury;Intervention, Genetic;Intrathecal Injections;Ion Channel;Ion Pumps;Ionic Channels;Kolliker's Reticulum;Left;Light;Lighting;Lumbar Puncture;Mammals, Mice;Mammals, Rats;Mammals, Rodents;Measures;Mediating;Membrane Channels;Membrane Potentials;Mental Depression;Methods And Techniques;Methods, Other;Mice;Molecular Biology;Molecular Biology, Gene Therapy;Motor Cell;Motor Neurons;Murine;Mus;Nerve;Nerve Cells;Nerve Unit;Nervous;Nervous System, Cns;Neural Cell;Neuraxis;Neurocyte;Neuroglia;Neuroglial Cells;Neuromodulator;Neurons;Neurons, Afferent;Neurons, Sensory;Neurophysiology / Electrophysiology;Neurosciences;Nociception;Non-Neuronal Cell;Operation;Operative Procedures;Operative Surgical Procedures;Opsin;Optics;Pain;Pain Control;Pain Therapy;Pain Management;Painful;Pathway Interactions;Patients;Peripheral;Phase;Photoradiation;Physical Health Services / Rehabilitation;Physiologic;Physiological;Physiology;Population;Preparation;Production;Productivity;Promoter;Promoters (Genetics);Promotor;Promotor (Genetics);Proteins;Proton Pump;Psyche Structure;Pump;Qol;Quality Of Life;Radiation, Visible;Radiation, Visible Light;Rat;Rattus;Rehabilitation;Rehabilitation Therapy;Rehabilitation, Medical;Research;Rest;Resting Potentials;Retinal;Retinal Degeneration;Rod-Opsin;Rodent;Rodentia;Rodentias;Sbir;Sbirs (R43/44);Sp(1-11);Salivary Gland Viruses;Scientist;Sensation;Sensory;Sensory Cell Afferent Neuron;Serotyping;Small Business Innovation Research;Small Business Innovation Research Grant;Specificity;Spinal Ganglia;Spinal Puncture;Spinal Cord Posterior Horn;Stimulus;Substance P;Surgical;Surgical Interventions;Surgical Procedure;Techniques;Technology;Testing;Therapeutic;Therapy, Dna;Toxic Effect;Toxicities;Transgenes;Transmembrane Potentials;Treatment Side Effects;United States;Visible Light;Visible Radiation;Adeno Associated Virus Group;Adeno-Associated Viral Vector;Adeno-Associated Virus Vector;Allodynia;Base;Blind;Cdna;Cell Transduction;Cellular Transduction;Chronic Neuropathic Pain;Chronic Pain;Chronic Painful Condition;Cognitive Dysfunction;Cognitive Loss;Cognitively Impaired;Complementary Dna;Cytomegalovirus Group;Design And Construction;Disease /Disorder;Disease/Disorder;Dorsal Root Ganglion;Experience;Failure;Gene Product;Gene Therapy;Genetic Therapy;Genetics;Human Cytomegalovirus;Imaging;Improved;In Vivo;Mental;Microbial;Motoneuron;Mouse Model;Nerve Cement;Neural;Neural Control;Neural Regulation;Neurokinin 1;Neuronal;Neuropathic Pain;Neuroregulation;New Technology;Nociceptive;Novel;Painful Neuropathy;Patch Clamp;Pathway;Phase 1 Study;Preprotachykinin A;Rehabilitative;Relating To Nervous System;Response;Retina Degeneration;Retinal Degenerative;Side Effect;Site Targeted Delivery;Spinal Ganglion;Surgery;Targeted Delivery;Therapeutic Gene;Therapy Adverse Effect;Transduced Cells;Transfer Of A Gene;Treatment Adverse Effect;Trial Regimen;Trial Treatment;Vector
