Theragnostic Technologies Inc. — Department of Health and Human Services SBIR Phase II: 400

Description

DESCRIPTION provided by applicant This SBIR phase project focuses on preclinical investigational new drug IND enabling studies of a novel high performance carbon nanostructure based magnetic resonance imaging MRI contrast agent CA to be used to diagnose and monitor patients with renal failure Every year in the US approximately million people are treated for mild to severe renal failure A significant number of cases greater than related to renal failure are at an advanced stage and lead to incidences of morbidity mortality and increase burden on health care resources and costs Non invasive imaging of renal injury or disease especially at advanced stages and or other pathologies lesions in patients with renal failure is still a major challenge in clinic X ray computed tomography CT and MRI are routinely used in clinic to image the anatomy of kidneys and other organs Exogenous chemicals called contrast agents CAs synthesized using the elements iodine and gadolinium has been widely employed to improve the diagnostic confidence of CT and MRI respectively However in patients with advanced renal failure these CAs have been linked to the onset of nephrotoxicity or the rare but potentially fatal disease nephrogenic systemic fibrosis NSF We have recently developed a novel carbon nanostructure based MRI CA that comprises of high quality graphene single sheet of graphite nanoparticles GNPs intercalated chemical species inserted and trapped in the voids between two graphene sheets and coordinated with graphene trace amounts of manganese and coated with natural biocompatible FDA approved polymer dextran hereafter called GNP Dex Our in vitro and in vivo normal rats and rat model of chronic kidney disease safety and efficacy studies pre phase and during phase of this novel MRI CA showed good hemodynamic characteristics increased in vivo circulation time blood half life of hour low acute toxicity lethal dose LD value andgt mg kg no chronic toxicity at therapeutic doses no acute or chronic nephrotoxicity including no NSF like indicators and greater contrast enhancement times greater compared to clinical Gd based MRI CAs These formed the basis of our recent request for an initial pre IND meeting with the FDA August Based on feedback from regulatory experts and FDA the overall objective of SBIR phase proposal is to scale up the manufacturing for GNP Dex using GMPs practices for use in preclinical studies and to conduct of preclinical GLP safety and non GLP efficacy studies in small and large animals Successful completion of these aims will represent a critical step in accelerating the translation of this technology to the clinic we anticipate that following completion of these aims we will initiate te first in human trials The final commercial product s will the first FDA approved MRI CA for patients with renal failure GNP Dex will also prove useful as an alternative MRI CA to currently existing clinical first pass and blood pool T MRI CAs PUBLIC HEALTH RELEVANCE Every year in the US approximately million people are treated for mild to severe clinical cases of kidney disease or injury also known as renal failure A significant number of these clinical cases greater than million involve advanced stage renal failure and lead to incidences of morbidity mortality and increase burden on health care resources and costs Non invasive imaging and monitoring of the kidneys during renal failure especially at these advanced stages is still a major challenge in clinic X ray computed tomography CT and magnetic resonance imaging MRI are routinely used in clinic for this purpose Exogenous chemicals called contrast agents CAs synthesized using the elements iodine and gadolinium has been employed to improve the diagnostic confidence of CT and MRI respectively However use of these CAs in patients with renal failure have been associated with nephrotoxicity and in some rare cases can lead to death This proposal describes the pre clinical development of a novel high performance carbon nanoparticle based MRI CA that comprises of high quality graphene single sheet of graphite nanoparticles disk shaped diameter nm thickness nm sheets of graphene also called graphene nanoplatelets or GNPs intercalated chemical species inserted and trapped in the voids between two graphene sheets and coordinated with graphene trace amounts of manganese w w w weight that can achieve times greater contrast enhancement at clinical dosages compared to current clinical MRI CAs and is not nephrotoxic for the imaging and monitoring of patients with renal failure