SBIR-STTR Award

Human Ghrelin as an Effective Mitigator of Acute Radiation Injury
Award last edited on: 9/26/2017

Sponsored Program
SBIR
Awarding Agency
NIH : NIAID
Total Award Amount
$3,551,800
Award Phase
2
Solicitation Topic Code
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Principal Investigator
Weng-Lang Yang

Company Information

TheraSource LLC

350 Community Drive
Manhasset, NY 11030
   (516) 562-1370
   info@therasourcellc.com
   www.therasourcellc.com
Location: Single
Congr. District: 03
County: Nassau

Phase I

Contract Number: 1R43AI096777-01
Start Date: 7/20/2011    Completed: 6/30/2013
Phase I year
2011
Phase I Amount
$297,826
This SBIR Phase I proposal is intended to demonstrate the feasibility of developing a novel and effective therapeutic approach that can save lives of people with radiation injury. Acute radiation injury may occur in various incidents as well as the terrorist radiation exposure scenario. Acute radiation syndrome develops after whole-body or a partial-body irradiation with a high dose of radiation. Despite advances in our understanding of the pathophysiology of acute radiation injury, the management of acute radiation syndrome is mainly supportive. Very little information is available on the specific treatment approaches to acute radiation injury. As such, there is an urgent unmet medical need for an effective novel mitigator for patients with acute radiation injury. Ghrelin, a gastrointestinal peptide, was first identified as an endogenous ligand for the growth hormone secretagogue receptor type 1a (i.e., ghrelin receptor). Ghrelin was originally reported to induce growth hormone release through stimulation of ghrelin receptors in the central nervous system. A large body of evidence has indicated other physiological properties of ghrelin mediated by the central and peripheral ghrelin receptors. Although human ghrelin has been shown to be beneficial in certain disease conditions, it remains unknown whether this peptide can mitigate acute radiation syndrome. To study this, adult male rats were exposed to 10-Gy total body irradiation (TBI). Our preliminary data have shown that administration of human ghrelin 6 h after TBI (i.e., very early treatment) reduced mortality. However, it remains unknown whether delayed administration of human ghrelin (which is more clinically relevant) reduces TBI-induced mortality as well. We, therefore, hypothesize that delayed administration of human ghrelin after TBI attenuates tissue injury and improves survival. The primary objective of this SBIR Phase I project is targeted towards demonstrating the feasibility of the development and commercialization of human ghrelin as an effective mitigator (24 h post-radiation or later) in reducing the massive mortality after acute radiation exposure scenario. The optimal dosage(s) of human ghrelin (delayed treatment) will be determined by assessing 1) the dose-response effect of ghrelin tissue injury after TBI;2) the dose-response effect and time-course of human ghrelin on TBI-induced mortality;and 3) the pharmacokinetics of human ghrelin in healthy and irradiated animals. Our ultimate goal (SBIR Phase II and beyond) is to obtain commercial utilization of human ghrelin as a safe and effective mitigator for people with acute radiation injury.

Public Health Relevance:
In the wake of the September 11, 2001 terrorist attacks, the misuse of ionizing radiation or nuclear devices as weapons of terrorism has been recognized as a major public health threat. Despite advances in our understanding of the pathophysiology of acute radiation injury, the management of acute radiation syndrome is mainly supportive. Very little information is available on the specific therapeutic approaches to radiation injury. Thus, there is an urgent unmet medical need for a novel and effective mitigator for people with acute radiation injury.

Thesaurus Terms:
2-Amino-1,5-Dihydro-1-Methyl-4h-Imidazol-4-One;21+ Years Old;Acute;Adult;Adult Human;After Care;After-Treatment;Aftercare;Animals;Apopain;Apoptosis;Apoptosis Pathway;Apoptosis-Related Cysteine Protease Caspase 3;Area Under Curve;Attenuated;Autopsy;B Cell Differentiation Factor;B Cell Stimulating Factor 2;B-Cell Differentiation Factor;B-Cell Differentiation Factor-2;B-Cell Stimulatory Factor-2;Bcdf;Bsf-2;Bsf2;Bsf2 (B Cell Stimulating Factor 2);Bizzozero's Corpuscle/Cell;Blood Coagulation Disorders;Blood Plasma;Blood Platelets;Blood Serum;Blood Erythrocyte;Blood Leukocyte;Blood Normocyte;Body Tissues;Body Weight;Casp-3;Casp3;Cns Nervous System;Cpp-32;Cpp32;Cpp32 Protein;Cpp32b;Cpp32beta;Central Nervous System;Cleaved Cell;Clinical Trials;Clotting;Coagulation;Coagulation Disorder;Coagulation Process;Coagulopathy;Common Rat Strains;Complete Blood Count;Creatinine;Cysteine Protease Cpp32;Dif;Data;Deetjeen's Body;Development;Devices;Disease;Disorder;Dose;Drug Kinetics;Drugs;Dysfunction;Early Treatment;Enzymes;Erythrocytes;Erythrocytes Reticuloendothelial System;Erythrocytic;Functional Disorder;Future;Ghs-R Type 1a;Ghs-R1a;Goals;Growth Hormone;Growth Hormone 1;H And E;Hmg-1/-2;Hmg-B;Hmg-Box Proteins;Hmgb;Hmgb Family Protein;Hmgb Proteins;Hpgf;Half-Life;Hayem's Elementary Corpuscle;Heart;Hematoxylin And Eosin;Hematoxylin And Eosin Staining Method;Hepatocyte-Stimulating Factor;High Mobility Group Box Proteins;Hybridoma Growth Factor;Ifn-Beta 2;Ifnb2;Il-6;Il6 Protein;Inflammatory Response;Injury;Interleukin 6 (Interferon, Beta 2);Interleukin-6;Ionizing Electromagnetic Radiation;Ionizing Radiation;Kidney;Kidney Urinary System;Loinc Axis 2 Property;Label;Leukocytes;Leukocytes Reticuloendothelial System;Ligands;Liver;Lung;Lung Respiratory System;Mgi-2;Marrow Erythrocyte;Marrow Leukocyte;Marrow Platelet;Measurement;Measures;Mediating;Medical;Medication;Monitor;Mortality;Mortality Vital Statistics;Myeloid Differentiation-Inducing Protein;Neuraxis;Nuclear;Parp Cleavage Protease;Patients;Peptides;Peripheral;Pharmaceutic Preparations;Pharmaceutical Preparations;Pharmacokinetics;Phase;Physiologic;Physiological;Physiopathology;Pituitary Growth Hormone;Plasma;Plasma Serum;Plasmacytoma Growth Factor;Platelets;Platelets Reticuloendothelial System;Programmed Cell Death;Property;Public Health;Radiation;Radiation Injuries;Radiation Syndromes;Radiation-Ionizing Total;Rat;Rats Mammals;Rattus;Red Blood Cells;Red Cell;Red Blood Corpuscule;Reporting;Reticuloendothelial System, Serum, Plasma;Risk;Sbir;Sbirs (R43/44);Sca-1;Srebp Cleavage Activity 1;Serum;Small Business Innovation Research;Small Business Innovation Research Grant;Small Intestines;Somatotropin;Spleen;Spleen Reticuloendothelial System;Staining Method;Stainings;Stains;Tnf;Tnf A;Tnf Gene;Tnfsf2;Tunel Assay;Tdt-Mediated Dutp Nick End Labeling Assay;Terrorism;Testing;Therapeutic;Thrombocytes;Time;Tissues;Total Body Irradiation;Tumor Necrosis Factor Gene;Western Blotting;Western Immunoblotting;White Blood Cells;White Cell;Whole-Body Irradiation;Whole-Body Radiation;Yama;Yama Protein;Adult Human (21+);Adulthood;Blood Corpuscles;Caspase-3;Cleaved;Clinical Investigation;Clinical Relevance;Clinically Relevant;Clotting Disorder;Commercialization;Cysteine Protease P32;Cytokine;Developmental;Disease/Disorder;Dosage;Drug Clearance;Drug/Agent;Early Intervention;Early Therapy;Gastrointestinal;Ghrelin;Ghrelin Receptor;Growth Hormone Secretagogue 1a Receptor;Growth Hormone Secretagogue Receptor Type 1a;Hepatic Body System;Hepatic Organ System;Human Ghrelin;Improved;Interferon Beta 2;Irradiation;Male;Necropsy;Novel;Pathophysiology;Phase 2 Study;Phase Ii Study;Post Treatment;Postmortem;Pre-Clinical Study;Pre-Clinical Trial;Preclinical Study;Preclinical Trial;Protein Blotting;Public Health Medicine (Field);Pulmonary;Ray (Radiation);Renal;Response;Small Bowel;Somatotropic Hormone;Thrombocyte/Platelet;Weapons;White Blood Cell;White Blood Corpuscle

Phase II

Contract Number: 5R43AI096777-02
Start Date: 00/00/00    Completed: 00/00/00
Phase II year
2012
(last award dollars: 2018)
Phase II Amount
$3,253,974

This SBIR Phase I proposal is intended to demonstrate the feasibility of developing a novel and effective therapeutic approach that can save lives of people with radiation injury. Acute radiation injury may occur in various incidents as well as the terrorist radiation exposure scenario. Acute radiation syndrome develops after whole-body or a partial-body irradiation with a high dose of radiation. Despite advances in our understanding of the pathophysiology of acute radiation injury, the management of acute radiation syndrome is mainly supportive. Very little information is available on the specific treatment approaches to acute radiation injury. As such, there is an urgent unmet medical need for an effective novel mitigator for patients with acute radiation injury. Ghrelin, a gastrointestinal peptide, was first identified as an endogenous ligand for the growth hormone secretagogue receptor type 1a (i.e., ghrelin receptor). Ghrelin was originally reported to induce growth hormone release through stimulation of ghrelin receptors in the central nervous system. A large body of evidence has indicated other physiological properties of ghrelin mediated by the central and peripheral ghrelin receptors. Although human ghrelin has been shown to be beneficial in certain disease conditions, it remains unknown whether this peptide can mitigate acute radiation syndrome. To study this, adult male rats were exposed to 10-Gy total body irradiation (TBI). Our preliminary data have shown that administration of human ghrelin 6 h after TBI (i.e., very early treatment) reduced mortality. However, it remains unknown whether delayed administration of human ghrelin (which is more clinically relevant) reduces TBI-induced mortality as well. We, therefore, hypothesize that delayed administration of human ghrelin after TBI attenuates tissue injury and improves survival. The primary objective of this SBIR Phase I project is targeted towards demonstrating the feasibility of the development and commercialization of human ghrelin as an effective mitigator (24 h post-radiation or later) in reducing the massive mortality after acute radiation exposure scenario. The optimal dosage(s) of human ghrelin (delayed treatment) will be determined by assessing 1) the dose-response effect of ghrelin tissue injury after TBI; 2) the dose-response effect and time-course of human ghrelin on TBI-induced mortality; and 3) the pharmacokinetics of human ghrelin in healthy and irradiated animals. Our ultimate goal (SBIR Phase II and beyond) is to obtain commercial utilization of human ghrelin as a safe and effective mitigator for people with acute radiation injury.

Public Health Relevance Statement:
In the wake of the September 11, 2001 terrorist attacks, the misuse of ionizing radiation or nuclear devices as weapons of terrorism has been recognized as a major public health threat. Despite advances in our understanding of the pathophysiology of acute radiation injury, the management of acute radiation syndrome is mainly supportive. Very little information is available on the specific therapeutic approaches to radiation injury. Thus, there is an urgent unmet medical need for a novel and effective mitigator for people with acute radiation injury.

Project Terms:
Acute; Adult; Aftercare; Animals; Apoptosis; Area Under Curve; Attenuated; Autopsy; Blood Coagulation Disorders; Blood Platelets; Body Weight; caspase-3; Cleaved cell; Clinical Trials; clinically relevant; Coagulation Process; commercialization; Complete Blood Count; Creatinine; cytokine; Data; Development; Devices; Disease; dosage; Dose; drug clearance; Drug Kinetics; Early treatment; Enzymes; Erythrocytes; Functional disorder; Future; gastrointestinal; ghrelin; ghrelin receptor; GHS-R1a; Goals; Half-Life; Heart; Hematoxylin and Eosin Staining Method; HMGB Proteins; human ghrelin; improved; Inflammatory Response; Injury; Interleukin-6; Ionizing radiation; irradiation; Kidney; Label; Leukocytes; Ligands; Liver; Lung; male; Measurement; Measures; Mediating; Medical; Monitor; Mortality Vital Statistics; Neuraxis; novel; Nuclear; Patients; Peptides; Peripheral; Pharmaceutical Preparations; Phase; phase 2 study; Physiological; Plasma; preclinical study; Property; public health medicine (field); Radiation; Radiation Injuries; Radiation Syndromes; Rattus; Reporting; response; Risk; Serum; Small Business Innovation Research Grant; Small Intestines; Somatotropin; Spleen; Staining method; Stains; TdT-Mediated dUTP Nick End Labeling Assay; Terrorism; Testing; Therapeutic; Time; Tissues; TNF gene; weapons; Western Blotting; Whole-Body Irradiation