SBIR-STTR Award

Sirna Mediated Modulation Of Lynx1 For Cognitive Enhancement
Award last edited on: 10/10/12

Sponsored Program
SBIR
Awarding Agency
NIH : NIMH
Total Award Amount
$656,365
Award Phase
2
Solicitation Topic Code
-----

Principal Investigator
Andreas Walz

Company Information

Ophidion Inc

2275 East Foothill Boulevard
Pasadena, CA 91107
   (646) 303-0621
   andreas.walz@ophidionbio.com
   www.ophidionbio.com
Location: Single
Congr. District: 27
County: Los Angeles

Phase I

Contract Number: 1R43MH094004-01
Start Date: 6/3/11    Completed: 4/30/13
Phase I year
2011
Phase I Amount
$328,017
The proposed project details a biologic strategy for the therapeutic targeting of nicotinic receptors of the cholinergic system for the treatment of mental and neurological disorders. The cholinergic system is an important modulatory neurotransmitter system, regulating reward, learning and memory, attention, and cognitive functions. The nicotinic acetylcholine receptor, a major receptor of the cholinergic system, is regulated by modulatory accessory proteins which bind to nicotinic acetylcholine receptors and dampen their function. Biological proof of concept studies in our mouse models indicate that regulating cholinergic tone has a beneficial enhancement of complex circuits in the brain, leading to enhanced learning and memory function. In order to develop a therapeutic intervention recapitulating this cognitive enhancement, we propose to develop a biological therapeutic to enhance cholinergic tone in the brain through accessory molecules to nicotinic receptors. Because the blood brain barrier is the most challenging problem facing the delivery of the macromolecules to neurons in the brain, we propose several strategies for optimizing delivery based on peptides with demonstrated ability to deliver therapeutic candidates past the blood- brain barrier. We will couple the most efficient translocators. We will test the functional inhibition by therapeutic candidates on our established nicotinic receptor cell lines and assays. In addition, we will label potential carrier molecules to assess their blood-brain penetrability, and finally test the efficacy of candidates in vivo in our mouse models. If successful the outcome will lead to the development of a therapeutic candidate to treat cognitive and memory impairments associated with mental and neurological disorders, such as schizophrenia, Alzheimer's and Parkinson's disease, and depression.

Public Health Relevance:
This project involves the development of therapeutic interventions to treat the cognitive dysfunction associated with mental and neurological disorders, such as schizophrenia, Alzheimer's disease, Parkinson's disease, depression, and ADHD.

Thesaurus Terms:
Ad/Hd;Adhd;Alzheimer;Alzheimer Disease;Alzheimer Sclerosis;Alzheimer Syndrome;Alzheimer's;Alzheimer's Disease;Alzheimers Dementia;Alzheimers Disease;Animals;Assay;Associative Learning;Attention;Attention Deficit Hyperactivity Disorder;Attention-Deficit Disorder, Predominantly Hyperactive-Impulsive Type;Back;Binding;Binding (Molecular Function);Bioassay;Biologic Assays;Biological;Biological Assay;Blood;Blood - Brain Barrier Anatomy;Blood-Brain Barrier;Blotting, Western;Brain;Bungarotoxins;Cell Line;Cell Lines, Strains;Cellline;Cells;Cholinergic Receptors;Cholinoceptive Sites;Cholinoceptors;Cognition;Cognitive;Cognitive Disturbance;Cognitive Impairment;Cognitive Decline;Cognitive Deficits;Cognitive Function Abnormal;Complex;Conditioning, Classical;Conditionings, Classical;Coupled;Dementia, Alzheimer Type;Dementia, Primary Senile Degenerative;Dementia, Senile;Depression;Development;Disease;Disorder;Disturbance In Cognition;Dorsum;Encephalon;Encephalons;Environment;Fluorescence;Genes;Goals;Healthcare Systems;Hemato-Encephalic Barrier;Hyperactivity Disorder Nos;Hyperactivity Disorder, Predominantly Hyperactive-Impulsive Type;Hyperkinetic Syndrome;Idiopathic Parkinson Disease;Impaired Cognition;Investigation;Knock-Out;Knockout;Knockout Mice;Label;Lead;Learning;Lewy Body Parkinson Disease;Mammals, Mice;Marketing;Measures;Memory;Memory Deficit;Memory Impairment;Mental Depression;Mental Disorders;Mental Health Disorders;Methods;Methods And Techniques;Methods, Other;Mice;Mice, Knock-Out;Mice, Knockout;Molecular Interaction;Monitor;Murine;Mus;Nerve Cells;Nerve Transmitter Substances;Nerve Unit;Nervous System Diseases;Nervous System, Brain;Neural Cell;Neurocyte;Neurologic Disorders;Neurological Disorders;Neurons;Neurotransmitters;Nicotinic Acetylcholine Receptors;Nicotinic Receptors;Null Mouse;Outcome;Paralysis Agitans;Parkinson;Parkinson Disease;Parkinson's;Parkinson's Disease;Parkinsons Disease;Patients;Pavlovian Conditioning;Pb Element;Peptides;Phase;Physiologic;Physiological;Post-Transcriptional Gene Silencing;Post-Transcriptional Gene Silencings;Posttranscriptional Gene Silencing;Posttranscriptional Gene Silencings;Primary Parkinsonism;Primary Senile Degenerative Dementia;Proteins;Psychiatric Disease;Psychiatric Disorder;Qol;Quality Of Life;Quelling;Rna Interference;Rna Silencing;Rna Silencings;Rna, Small Interfering;Rnai;Rt-Pcr;Rtpcr;Receptor Cell;Receptors, Ach;Receptors, Acetylcholine;Reticuloendothelial System, Blood;Reverse Transcriptase Polymerase Chain Reaction;Rewards;Schizophrenia;Schizophrenic Disorders;Sequence-Specific Posttranscriptional Gene Silencing;Small Interfering Rna;Specificity;Staging;System;System, Loinc Axis 4;Systems, Health Care;Techniques;Testing;Therapeutic;Therapeutic Intervention;Time;Toxic Effect;Toxicities;Toxin;Transgenic Mice;Translating;Translatings;Unspecified Mental Disorder;Western Blotting;Western Blottings;Western Immunoblotting;Work;Attention Deficit Hyperactive Disorder;Base;Behavior Test;Behavioral Test;Blood Brain Barrier;Cholinergic;Classical Conditioning;Cognitive Dysfunction;Cognitive Enhancement;Cognitive Function;Cognitive Loss;Cognitively Impaired;Cultured Cell Line;Dementia Of The Alzheimer Type;Dementia Praecox;Disease /Disorder;Disease/Disorder;Dosage;Effective Therapy;Efficacy Testing;Established Cell Line;Extracellular;Falls;Gene Product;Glycoprotein G, Rabies Virus;Heavy Metal Pb;Heavy Metal Lead;Immunogenicity;In Vivo;Intervention Therapy;Language Translation;Macromolecule;Member;Mental Illness;Mouse Model;Nervous System Disorder;Neurological Disease;Neuronal;Primary Degenerative Dementia;Protein Blotting;Psychological Disorder;Rabies Virus G Protein;Rabies Virus Glycoprotein;Rabies Virus Glycoprotein G;Receptor Function;Reverse Transcriptase Pcr;Schizophrenic;Senile Dementia Of The Alzheimer Type;Sirna;Small Interfering Rna;Therapeutic Target

Phase II

Contract Number: 5R43MH094004-02
Start Date: 00/00/00    Completed: 00/00/00
Phase II year
2012
Phase II Amount
$328,348
The proposed project details a biologic strategy for the therapeutic targeting of nicotinic receptors of the cholinergic system for the treatment of mental and neurological disorders. The cholinergic system is an important modulatory neurotransmitter system, regulating reward, learning and memory, attention, and cognitive functions. The nicotinic acetylcholine receptor, a major receptor of the cholinergic system, is regulated by modulatory accessory proteins which bind to nicotinic acetylcholine receptors and dampen their function. Biological proof of concept studies in our mouse models indicate that regulating cholinergic tone has a beneficial enhancement of complex circuits in the brain, leading to enhanced learning and memory function. In order to develop a therapeutic intervention recapitulating this cognitive enhancement, we propose to develop a biological therapeutic to enhance cholinergic tone in the brain through accessory molecules to nicotinic receptors. Because the blood brain barrier is the most challenging problem facing the delivery of the macromolecules to neurons in the brain, we propose several strategies for optimizing delivery based on peptides with demonstrated ability to deliver therapeutic candidates past the blood- brain barrier. We will couple the most efficient translocators. We will test the functional inhibition by therapeutic candidates on our established nicotinic receptor cell lines and assays. In addition, we will label potential carrier molecules to assess their blood-brain penetrability, and finally test the efficacy of candidates in vivo in our mouse models. If successful the outcome will lead to the development of a therapeutic candidate to treat cognitive and memory impairments associated with mental and neurological disorders, such as schizophrenia, Alzheimer's and Parkinson's disease, and depression.