Very compelling data are available to suggest oxidative stress is an underlying component of many significant human diseases such as diabetes, heart disease, cerebrovascular disease (eg, stroke), peripheral vascular disease, neurodegeneration (Alzheimer's, Parkinson's, ALS and Huntington's disease) as well as aging. However, results to date with antioxidant treatments to mitigate human diseases with oxygen stress as an underlying component of the pathology have been disappointing. Tosk, Inc. has successfully designed an agent to irreversibly bind a traditional antioxidant to an enzyme located in the region where reactive oxygen species are formed. This was done to make the traditional antioxidant more effective. Now Tosk requests Phase I SBIR funding to further explore this approach to produce even more active antioxidants. A total of 15 novel antioxidants will be synthesized and tested in the same animal model used originally to discover the activity of the new antioxidant designed at Tosk. Three of the synthesized molecules will also be tested in one additional animal model of human disease associated with excess oxidative stress as a significant part of the condition's underlying pathology.
Public Health Relevance: Results to date with antioxidant treatments to mitigate human diseases having oxygen stress as an underlying component of the pathology have been disappointing. Tosk, Inc. has successfully designed an agent to irreversibly bind a traditional antioxidant to an enzyme located in the region where reactive oxygen species are formed. This was done to make the traditional antioxidant more effective. Now Tosk requests Phase I SBIR funding to further explore this approach to produce more active antioxidants as well as to evaluate the approach in one additional animal model of human disease associated with excess oxidative stress as a significant part of the conditions underlying the pathology.
Thesaurus Terms: "(8s-Cis)-10-[(3-Amino-2,3,6-Trideoxy-Alpha-L-Lyxo-Hexopyranosyl)Oxy]-7,8,9,10-Tetrahydro-6,8,11-Trihydroxy-8-(Hydroacetyl)-1-Methoxy-5,12-Naphthacenedione; 14-Hydroxydaunomycin; 5,12-Naphthacenedione, 10-((3-Amino-2,3,6-Trideoxy-Alpha-L-Lyxo-Hexopyranosyl)Oxy)-7,8,9,10-Tetrahydro-6,8,11-Trihydroxy-8-(Hydroxyacetyl)-1-Methoxy-, (8s-Cis)-; Active Oxygen; Adriamycine; Affect; Affinity; Aging; Alzheimer; Alzheimer Disease; Alzheimer Sclerosis; Alzheimer Syndrome; Alzheimer's; Alzheimer's Disease; Alzheimers Dementia; Alzheimers Disease; Animal Model; Animal Models And Related Studies; Anthracycline Antibiotics; Antioxidants; Apoplexy; Applications Grants; Area; Assay; Binding; Binding (Molecular Function); Bioassay; Biologic Assays; Biological; Biological Assay; Blood Plasma; Brain Vascular Disorders; Cancer Patient; Cancer Cell Line; Cancers; Cardiac; Cardiac Diseases; Cardiac Disorders; Cardiolipins; Cardiomyopathies; Causality; Cerebral Stroke; Cerebrovascular Apoplexy; Cerebrovascular Disease; Cerebrovascular Disorders; Cerebrovascular Stroke; Cerebrovascular Accident; Chemotherapy, Cancer, Anthracyclines; Clinical; Common Rat Strains; Dox; Data; Dementia, Alzheimer Type; Dementia, Primary Senile Degenerative; Dementia, Senile; Development; Diabetes Mellitus; Disease; Disorder; Dose; Doxorubicin; Doxorubicina; Elements; Enzymes; Etiology; Evaluation; Funding; Goals; Grant Proposals; Grants, Applications; Half-Life; Half-Lifes; Heart; Heart Diseases; Hematologic Cancer; Hematologic Malignancies; Hematologic Neoplasms; Hematological Malignancies; Hematological Neoplasms; Hematological Tumor; Hematopoietic Cancer; History; Hour; Human; Human, General; Huntington Chorea; Huntington Disease; Huntington's; Huntington's Disease; Huntington's Disease Pathway; Huntingtons Disease; Hydroxyl Daunorubicin; Hydroxyldaunorubicin; Idiopathic Parkinson Disease; In Vitro; Intracranial Vascular Disorders; Lead; Lewy Body Parkinson Disease; Life; Lytotoxicity; Malignant Hematologic Neoplasm; Malignant Neoplasms; Malignant Tumor; Mammals, Mice; Mammals, Rats; Man (Taxonomy); Man, Modern; Measurable; Measures; Mediator; Mediator Of Activation; Mediator Of Activation Protein; Membrane; Mice; Middle Cerebral Artery Occlusion; Mitochondria; Modeling; Molecular Interaction; Murine; Mus; Mycocardium Disease; Myocardial Diseases; Myocardial Disorder; Myocardiopathies; Noael; Nerve Degeneration; Neuron Degeneration; No-Observed-Adverse-Effect Level; O Element; O2 Element; Organelles; Oxidative Stress; Oxygen; Oxygen Radicals; Paralysis Agitans; Parkinson; Parkinson Disease; Parkinson's; Parkinson's Disease; Parkinsons Disease; Pathologic; Pathology; Patients; Pb Element; Peripheral Angiopathies; Peripheral Vascular Diseases; Peripheral Vascular Disorder; Phase; Plasma; Primary Parkinsonism; Primary Senile Degenerative Dementia; Pro-Oxidants; Production; Progressive Chorea, Hereditary, Chronic (Huntington); Rat; Rattus; Reactive Oxygen Species; Recording Of Previous Events; Regimen; Research; Reticuloendothelial System, Serum, Plasma; Sbir; Sbirs (R43/44); Senescence; Serum, Plasma; Small Business Innovation Research; Small Business Innovation Research Grant; Solid; Stress; Stroke; Test Result; Testing; Therapeutic; Thioredoxin-2; Tni; Troponin I; Vascular Accident, Brain; Vascular Diseases, Intracranial; Anthracycline; Anti-Oxidant; Base; Brain Attack; Cerebral Vascular Accident; Cytotoxicity; Dementia Of The Alzheimer Type; Design; Designing; Diabetes; Disease Causation; Disease Etiology; Disease/Disorder; Disease/Disorder Etiology; Disorder Etiology; Drug Candidate; Heart Disorder; Heavy Metal Pb; Heavy Metal Lead; Human Disease; Improved; In Vivo; Inhibitory Troponin I; Malignancy; Membrane Structure; Mitochondrial; Mitochondrial Membrane; Model Organism; Myocardium Disorder; Neoplasm/Cancer; Neural Degeneration; Neurodegeneration; Neuronal Degeneration; Novel; Peripheral Blood Vessel Disorder; Pre-Clinical; Preclinical; Primary Degenerative Dementia; Protective Effect; Prototype; Public Health Relevance; Safety Study; Senescent; Senile Dementia Of The Alzheimer Type; Stroke"
