An eNAMPT-neutralizing mAb reduces post-infarct myocardial fibrosis and left ventricular dysfunction

Saad Sammani, Christy J Barber, Joshua Strom, Carrie Kempf, Tadeo Bermudez, Sara M Camp, Vivian Reyes Herndon, Lars R Furenlid, Joe G.N. Garcia

Research output: Working paper


Chronic inflammatory responses following myocardial ischemia-reperfusion injury (IRI) may lead to ventricular remodeling and heart failure. We hypothesize that a novel theranostic target, extracellular nicotinamide phosphoribosyl-transferase (eNAMPT), can afford specific detection and treatment of the inflammation-mediated adverse ventricular remodeling using an eNAMPT-neutralizing humanized monoclonal antibody (mAb). Methods: ALT-100 and ALT-300 mAb were derived from anti-human eNAMPT mAb-producing murine hybridomas. The ALT-300 mAb was 99mTc-labeled to generate 99mTc-ALT-300 as an imaging biomarker of myocardial eNAMPT expression by IV administration. Rat hearts with IRI were prepared by ligation of the left coronary artery (LCA) for 45-min followed by reperfusion. 99mTc-ALT-300 myocardial images were collected in the rat hearts with IRI at 2 h (n=1), 1 week (n=5), and 4 weeks (n=5) post LCA reflow. ALT-100 (0.8 mg/kg) (n=11) and carrier vehicle saline as control (n=11) were IV administered at 60 min and 24 h of reperfusion, respectively. Additional treatment doses were given by IP injection twice a week for 4 weeks. Cardiac function changes were determined by echocardiography. Results: 99mTc-ALT-300 imaging showed “hot-spot” radioactive uptake in the ischemic myocardium. The distribution of 99mTc-ALT-300 spread beyond the ischemic margins, extending substantially to non-ischemic myocardial areas, from 2 h to 4 weeks post-reperfusion. The uptake (%ID/g) of 99mTc-ALT-300 in the ischemic myocardium was significantly increased from 1 week to 4 weeks (0.54± 0.07 vs. 0.78 ± 0.07, P
Original languageEnglish (US)
StateSubmitted - 2022


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