Research Project
8918734
DESCRIPTION (provided by applicant): Coronary heart disease (CHD) accounts for every 1 of 6 deaths in the United States (US), with acute incidences estimated at 1.1M annually [1]. Of these, up to 40% are classified as ST-elevation myocardial infarction (STEMI) in which a clot blocks a coronary artery, leading to a change in the ECG ST wave [1] [5]. Because the heart muscle rapidly dies, time to reperfusion is critical [6] [7] [8]. While current CHD annual indirect costs are high, they are projected to further increase from $87B in 2013 to $130B by 2030 [9]. Early percutaneous coronary intervention (PCI) remains the standard of care in the US. However, PCI has not shown to be of benefit to STEMI patients living in rural communities due to increased transportation times. Efforts to expand PCI to rural communities have largely failed due to new PCI centers only being established in urban regions [10]. As a result, >80% of transferred STEMI patients do not receive PCI therapy within the recommended 120min from first medical contact, resulting in significantly higher mortality and greater patient costs [11] [2]. Given that over 60M people live in geographically remote or rural communities >60 miles from a PCI center, it is estimated that >175k STEMI victims will remain without timely access to PCI each year [3]. While clot-dissolving drugs are effective, most physicians remain uncomfortable with their elevated bleeding risk and sub-PCI recanalization rates [12] [3]. Fundamentally, thrombolytic drugs are limited in their effectiveness due to their inability to rapidly diffuse to clot in the occluded vessel due to poor fluid dynamics [13]. Pulse Therapeutics, Inc.'s (PTI's) patented and clinically-tested technology has overcome this limitation in a way that dramatically accelerates drug delivery to a clot by using non-drug attached magnetite particles controlled by a magnetic cart in the emergency department. However, by attaching the FDA-approved drug tenecteplase (TNK) to PTI's magnetite particles, the technology promises substantially faster clot lysis while eliminating associated bleeding risks, with therapy deliverable in both the community hospital and ambulance settings. Unfortunately, this strategy likely faces an expensive FDA combination-product regulatory pathway. PTI's objective is to demonstrate dramatic improvements in fibrinolysis by attaching TNK to magnetite particles. In Phase I, PTI will attempt to 1) develop a optimally-sized magnetite particle with the best- performing TNK coating conjugated to the magnetite surface, 2) collect data on candidate particle's clot lysis rates in vitro, 3) optimize a software algorithm for automated particle collection, 4) develop an ECG signal filtering system to enable the use of the technology without affecting electrocardiographic waveforms, and 5) conduct investigations evaluating lysis efficacy and hemorrhage risks in preclinical animal models. The proposed technology has dramatic implications for rural STEMI treatment and will address the American Heart Association's concern that Where you live should not determine whether you live. [14]
