B-BIC supports three new technologies for commercial development.

Warren Zapol, MD, Director of the MGH Anesthesia Center for Critical Care Research at Massachusetts General Hospital, receives a DRIVE award to develop electric nitric oxide generation for medical purposes.  Inhaled nitric oxide (NO) was approved by the FDA in December, 1999 as a life saving therapy producing selective pulmonary vasodilation in neonates with persistent pulmonary hypertension of the newborn (PPHN). Inhaled NO has a remarkable safety profile with no major side effects reported after 25 years of clinical use in over 500,000 pediatric and adult patients. There is also limited but compelling evidence that many other patients, including those with chronic obstructive pulmonary disease (COPD – Vonbank et al., 2003), idiopathic pulmonary fibrosis (IPF – Blanco et al., 2011), chronic pulmonary arterial hypertension (PAH – Benza et al., 2015) and congestive heart failure (CHF – Semigran et al., 1994) might benefit from NO. However these patients are neither currently treated with NO nor systematically studied to demonstrate the potential benefits of breathing NO, because of NO’s high cost and lack of portability. The Zapol team believes patients need less expensive and easier access to inhaled NO and a user-friendly, lightweight and portable inhaled NO to address chronic indications. The team will develop and test a portable and affordable lightweight NO generator, building on our published benchtop device that uses pulsed electrical discharges to generate NO from air.  This NO generator will expand the population of patients around the world who could benefit from NO inhalation therapy in-hospital by providing a cost-effective point-of-care solution and will accelerate research into chronic indications.

John Connor, PhD, Associate Professor of Microbiology at Boston University receives a DRIVE award for the elimination of pathogenic IgE in cystic fibrosis.  Allergic bronchopulmonary aspergillosis (ABPA) causes worsening of the respiratory condition in patients with cystic fibrosis (CF) and leads to bronchiectasis, fibrosis and loss of lung function. Treatment of ABPA also carries risk, as it can result in steroid dependency and serious adverse events.  Reduction of pathogenic IgE has been shown to improve respiratory symptoms and lung function in ABPA.   The Connor team is developing a novel biologic drug that has a dual mechanism: reduction of systemic IgE and inhibition of IgE-mediated pathological responses.  The drug is expected to be highly efficacious in reducing lung damage in CF.

Leo Tsai, MD, PhD, Staff Radiologist, Beth Israel Deaconess Medical Center; Co-Founder & CTO, Agile Devices receives a Pilot award to develop a microcatheter with variable stiffness for navigation of tortuous vessels.  Endovascular procedures performed by interventional radiologists, cardiologists, neurologists, and vascular surgeons often require navigation across small tortuous vessels to access their target lesion. Microcatheters are required to deploy embolic agents, thrombolytics, medications, stents or retrieval devices, or diagnostic contrast agents. Navigation to the target is usually achieved with a combination of guidewires and microcatheter, and becomes difficult when the microcatheter encounters a sharp turn.. Operators need to torque and repeatedly slide back/forth their catheter across sharp turns and may sometimes need to exchange for another device with a different stiffness if unsuccessful. This contributes to delays that add to material costs (e.g., OR time, additional devices) and clinical costs (e.g., delay in treatment, additional radiation exposure). Since microvessels are highly variable from patient to patient, procedure times for complex endovascular procedures are often highly unpredictable, which in turn reduces efficiency of the OR workflow. Current actively steerable catheter designs cannot be practically scaled down to the microvascular (mm) scale and operators currently rely solely on microcatheters with no active adjustment capabilities.  This work uses existing microcatheter components to construct and integrate a suite of device architectures using proprietary designs, varying stiffness, tip length and curvature, and handle design.  The team will test access times and navigational ability of the prototypes, with attention to torqueability and pushability,, determine mechanical and operational failure points, and compatibility with existing equipment, including sheaths, wires, coils, balloons, and stents.

Aditya Kaza, MD, Associate in Cardiac Surgery, Boston Children’s Hospital, Assistant Professor of Surgery, Harvard Medical School receives a Pilot award to develop confocal microscopy for intraoperative discrimination of cardiac conduction tissue.  Approximately 32,000 new cases of congenital heart defects occur in the US per year and there are ~1.5 million new cases worldwide. More than 20,000 congenital cardiac operations are performed each year in the US. Advances in diagnostic technologies, refinement of surgical techniques, and improvements in postoperative care have all contributed to favorable outcomes in this complex group of patients. However, there are several complications associated with surgical intervention.  Many of these complications require chronic cardiac rhythm management using implantable pacemakers. Despite the significant improvement in surgical results, there is still a critical barrier that needs to be overcome, which is to avoid preventable causes of conduction defects. This work will bring recently developed microscopic imaging technology to the operating room. Using real-time and portable fiber-optics confocal microscopy (FCM), the Kaza team has developed a systematic methodology for intraoperative identification of conduction tissue. Refinement and validation of this technology could potentially decrease the incidence of preventable causes of conduction delays in the operating room. Intraoperative microscopic imaging has the potential to assist heart surgeons by discriminating tissue types based on underlying structural and functional differences.

Gary Gilbert, MD, Veterans Affairs Boston Healthcare System, Associate Professor of Medicine, Harvard Medical School, receives a Pilot award to develop an improved factor VIII assay for activated platelet time.  Factor VIII activity assays are necessary to diagnose patients who have hemophilia A, to monitor treatment dosing of these patients, to determine when inhibitory antibodies against factor VIII have developed, and to evaluate the activity of engineered pharmaceutical factor VIII products. Factor VIII activity has been measured with evolving one and two-stage assays for fifty years. However, all existing assays have major shortcomings recognized by the FDA, the International Society for Thrombosis and Haemostasis, and pharmaceutical companies. The major deficiencies are: 1) In the presence of inhibitory antibodies, factor VIII asssays do not predict the risk of bleeding. The degree of inhibition in assays is less than required to explain patient bleeding. 2) The assays are only accurate over a range of 1 – 100% of normal factor VIII activity, while values of 0.1 – 1% are also clinically important. 3) The different approved assays give discrepant values for recombinant pharmaceutical factor VIII products, with a range of 2-fold difference between assays. This can lead to clinically important differences in dosing of factor VIII products from one region to another with corresponding risk of thrombosis or bleeding.

The Gilbert team has identified a method of improving the existing assay so that it has an extended activity range and is much more sensitive to inhibitory antibodies. This work will standardize a prototype, platelet-based factor VIII activity assay that resolves the identified problems.  Approx. 130,000 factor VIII assays are performed in the U.S. each year. A validated, platelet-based factor VIII assay would likely replace the majority of these tests.