Hospital Community
Technologies Under Development
2009 Technology Development Fund Awarded Projects
A Topical, Slow-Release Anti-Angiogenic Drug for Treating Eye Diseases
(Ofra Benny, PhD and Robert D'Amato, MD, PhD, Vascular Biology)
Project summary:
This projects aim is to develop a “ready-to use” antiangiogenic drug-delivery product for ophthamology uses. This project describes a method for treating ocular angiogenesis related diseases, comprising topical administration of Lodamin™ as an antiangiogenic polymeric drug. For this specific application, Lodamin, which was originally developed for oral anti-cancer therapy, will be reformulated in solution and optimized. Angiogenesis related eye diseases, such as retinal/choroidal neovascularization that includes diabetic retinopathy, macular degeneration, chronic uveitis/vitritis, infections, autoimmune diseases and retinopathy of prematurity are common. Effective anti-angiogenic therapies aim to delay the progression of some of these ophthalmic diseases and prevent vision loss. Currently there are no antiangiogenic drugs for corneal neovascularization but only indirect angiogenesis inhibitors such as steroids and immunosuppressants. For retinal angiogenesis-related diseases, such as Age-Related Macular Degeneration (AMD), the only antiangiogenic therapies available are based on targeting a single growth factor: Vascular Endothelial Growth Factor (VEGF). However, those therapies work mainly by decreasing vessel permeability, rather than inhibiting vessel growth, as does Lodamin. In addition, targeting a single growth factor can lead to either a resistance to the treatment over time or reduced efficacy over time, as other growth factors other than VEGF start playing a significant role in the progression of the disease. [more]
A Topical Treatment for Peripheral Neuropathies
(Gabriel Corfas, PhD, Neurobiology Program)
Project Summary:
Peripheral neuropathies, i.e. disorders of peripheral nerve function and structure, are commonly associated with diseases such as diabetes, HIV infection, and alcoholism. Current treatments for peripheral neuropathies are mostly targeted to eliminate symptoms such as pain. The goal is to develop new therapies to treat peripheral neuropathies. Dr. Corfas’ team has found that topical application of a small molecule acting on neurotrophic receptors is an effective therapeutic strategy, as demonstrated in two mouse models of small fiber peripheral neuropathy. The award will support studies to define key physical properties and biodistribution of the lead compound. Dr. Corfas believes that these studies will significantly clarify, and likely substantiate the commercial viability of this type of compound. The work is expected to enhance its potential for licensing and expedite its subsequent development as a therapeutic. [more]
Fetal Tissue Engineering to Repair Congenital Diaphragmatic Hernia
(Dario Fauza, MD, Surgery)
Project summary:
Congenital diaphragmatic hernia (CDH) is among the most common major structural congenital anomalies, occurring in approximately 1:2,200 births. It encompasses a defect in the diaphragm, allowing for herniation of abdominal organs into the chest. This project is aimed at the eventual approval of the first human trial of neonatal diaphragmatic repair with a mesenchymal amniocyte-based, autologous engineered graft. The team hopes to fulfill definite pending requirements, as specified by the FDA authorities governing such processes, and eventually bring this concept to clinical fruition. The precise strategy and experiments to be performed will depend on the FDA’s review of the latest data, early next fall. Two project scenarios can be foreseen. In the first, the FDA is satisfied with the current pre-clinical data and approves the first clinical trial. In that case, this award would be used to fund such a trial. In the second, the FDA requires additional pre-clinical large animal and cell manufacturing data before allowing the first clinical trial. In this case, this award would be used to accomplish such new demands. [more]
Semaphorin 3F as a Treatment for Prostate Cancer
(Elena Geretti, PhD and Michael Klagsbrun, PhD, Vascular Biology Program)
Project Summary:
Prostate cancer is the second most common diagnosed cancer type (preceded only by skin cancer) in American men and the second leading cause of cancer death, only behind lung cancer. Class-3 semaphorins were originally described in the neuronal system as axon guidance molecules; however their contribution to vascular/tumor biology is becoming evident. The goal of this project is to secure funds for producing recombinant SEMA3F, and for assessing their activity in in vivo studies in the TRAMP model of spontaneous mouse prostate tumor progression and metastasis. The overall goal is to develop SEMA3F as a novel cancer therapeutic. SEMA3F is a strong candidate as a new therapeutic because there is evidence that it is a robust inhibitor of both angiogenesis and, importantly, metastasis. [more]
A Pediatric Vision Scanner
(David Hunter, MD, PhD, Ophthalmology)
Project Summary:
Amblyopia ("lazy eye") and strabismus are two eye conditions that can blind an eye if left untreated. When a child has strabismus, the eyes are misaligned, and to prevent double vision, the child's brain suppresses the weaker one, eventually blinding it. Physicians have struggled to consistently detect and diagnose strabismus and amblyopia because the signs cannot always be detected by a competent primary care doctor. Dr. Hunter has developed the Pediatric Vision Scanner (PVS), a device that in a quick 2.5 second scan of the eyes can automatically detect strabismus, amblyopia, and other serious eye conditions in children as young as two years of age. In 2008, a pilot study of the PVS prototype involving over 200 subjects (article submitted for publication) showed unprecedented accuracy, with a sensitivity and specificity both exceeding 97 percent. There is only one existing current version of the PVS prototype, and that device contains extra components and circuitry that were required for initial development. Several lighter, easier-to-use prototypes are needed to allow for independent IRB-approved clinical trials at other institutions to assess its feasibility in the field and generate widespread acceptance of its effectiveness. [more]
Urine Diagnostic Markers of Acute Appendicitis
(Alex Kentsis, MD, Division of Hematology/Oncology, Richard Bachur, MD, Emergency Medicine, and Hanno Steen, PhD, Proteomics)
Project Summary:
Acute appendicitis is the most common surgical emergency, with the life time personal risk of nearly one in ten. Even with modern ultrasound and computed tomography imaging, accurate diagnosis of appendicitis is challenging, with as many as 10-30 percent of patients undergoing unnecessary surgeries, and as many as 30-45 percent of patients having delayed diagnosis, with associated increased mortality, morbidity, and cost. This team recently completed a study of discovery and validation of urine markers of acute pediatric appendicitis by using high accuracy mass spectrometry. They discovered several novel urine markers of acute appendicitis, with improved diagnostic performance as compared to ultrasound and CT imaging, as well as to known laboratory markers of acute appendicitis. Among these markers is the leucine-rich alpha-2-glycoprotein (LRG) that is enriched by several orders of magnitude in diseased appendices and in the urine of patients with appendicitis, and exhibits superior diagnostic performance, as assessed using receiver operating characteristic (ROC) area under the curve value of 0.97. This technology development award will fund the translation of the LRG test to an antibody based platform, and will further validate this biomarker for appendicitis. [more]
I.V. Oxygen Using Injectable Microbubbles
(John Kheir, MD, Anesthesia, Perioperative and Pain Medicine)
Project Summary:
The goal of this project is to package oxygen in such a way that it can be administered intravenously. Low oxygen levels are a final common pathway which causes death or severe disability in a variety of diseases affecting both adults and children. To address this, Dr. Kheir has developed a liquid suspension containing very high concentrations of oxygen gas packaged into microbubbles designed for intravenous injection. In this project, his team will expand the body of evidence in support of I.V. oxygen as a therapy. Specifically, they will test the efficacy of I.V. oxygen to improve outcomes during airway obstruction and during cardiac arrest. During the period of the study, they will utilize matching funds which have been awarded to this project from the Massachusetts Medical Device Development (M2D2) Center to fund improvements in manufacturing techniques, most specifically the creation of a sterile, continuous manufacturing system. [more]
A Novel Pneumococcal Vaccine
(Ying-Jie Lu, PhD, and Richard Malley, MD, Infectious Diseases)
Project Summary:
Dr. Malley and Dr. Lu have developed a new technology platform, to create new vaccines that elicit potent immunity to pneumococcus and other targets. Unlike current vaccines, a pneumococcal vaccine based on this technology will be effective in both developing and developed countries because it will include the coverage of all strains, induce both antibody and T cell responses to the organism, generate immunity to protect against invasive disease and mucosal carriage, and carry with it a lower cost and ease of manufacture. Because the vaccine elicits not only antibody, but also T cell immunity, which is quite different between mice and primates, this study is designed to confirm vaccine immunogenicity and safety in nonhuman primates. The main goal of this project is to evaluate the novel vaccine against pneumococcal colonization and disease in nonhuman primates. [more]
Development of Chemical Chaperones to Treat Obesity and Type 2 Diabetes
(Umut Ozcan, MD, Endocrinology)
Project Summary:
The discovery of leptin more than a decade ago heralded a potential therapeutic for the treatment of obesity; however, the enthusiasm surrounding leptin as a therapeutic agent diminished rapidly with the findings that both diet-induced rodent models of obesity and obese humans are minimally responsive to leptin due to development of leptin resistance in the brain. Dr. Ozcan’s team team has shown that drugs that alleviate ER stress can re-sensitize the brains of the obese mice to leptin and act as leptin sensitizers.
Dr. Ozcan’s and collaborators have discovered several new chemical chaperones, which have the ability to decrease ER stress at very low doses compared to previous agents. These have shown promising results in in vivo mouse models of obesity. This project builds on this recent data and aims to perform pharmacokinetics (PK) and toxicology studies for the three most powerful compounds. [more]
Development of Saposin A as a Cancer Therapeutic
(Randolph Watnick, PhD, Vascular Biology Program)
Project Summary:
Dr. Watnick identified an endogenous protein, saposin A, which is secreted by weakly aggressive human breast and prostate cancer cells, and has demonstrated that it inhibits metastasis in a prostate cancer model in vivo. One major advantage that saposin A, and its derivatives, would have over traditional therapies is the fact that its mode of action is directed toward the normal cells that make up the stroma of primary tumors and the parenchyma of normal organs. These cells are genetically stable and unlikely to develop mutations that would confer resistance to saposin A treatment. For this grant, Dr. Watnick will perform pre-clinical studies in murine xenograft and spontaneous tumor models. The goal is to confirm the efficacy of saposin A, and derivatives thereof, against tumor growth and determine specificity against several types of cancer. [more]
Hand-Held Solution to Improve Communication, Coordinate Emergency Department Care
(Debra Weiner, MD, PhD, Emergency Medicine)
Project Summary:
Emergency care in this country and throughout the world is in crisis. Increasing patient volume and decreasing Emergency Department (ED) resources threaten patient care and safety, as well the survival of EDs themselves. Solutions to improve patient services, as well as to maximize efficiency and lower costs, are desperately needed. Efficient and timely communication is critical for meeting these challenge, however, at present, communication is part of the problem. The goal of this project is to develop a workflow integrated communication network that coordinates ED patient care between the multitude of providers, services and systems within the ED and throughout the hospital to impact patient care and the health of the ED healthcare system.
Externally Funded Projects
The Active Bottle (CMCC 670, 1426, 1014):
(Eugene Goldfield, PhD, Psychiatry)
Preterm babies are unable to coordinate sucking, swallowing and breathing. To teach babies to coordinate these efforts, Dr. Eugene Goldfield, assistant professor in Psychiatry and a researcher at Children's Hospital Boston developed and demonstrated a system comprised of a nipple that is modified to include pressure sensors, a respiration sensor, and software to measure, display, and report respiration, expression, and sucking behavior during infant oral feeding.
There are several potential applications for the Active Bottle. In one application, the system regulates the flow of milk through continuous monitoring of real-time data on the baby's breathing and sucking activity. If the baby's breathing pattern falls below a specified normal threshold, then the Active Bottle withholds milk. If breathing remains above this threshold, then milk flows according to the baby's level of demand based on sucking activity.
In another application, the bottle is used to compensate for swallowing disorders such as neurogenic dysphagia and swallowing problems due to perinatal brain injury. Care of neurogenic dysphagia, which can affect premature infants born before 33 weeks of gestational age or born at term with congenital heart disease, may require a feeding protocol that manipulates the properties of the fluids being fed to the infants. In this instance, the Active Bottle is used for dispensing either thin-consistency or nectar-thick fluids to dysphagic infants on the basis of sucking, swallowing, and respiration sensor signals.
Since 2003, Children's Hospital has been collaborating with Foster-Miller Inc. (FMI) and Infoscitex Corporation (IST) to develop working prototypes for the Active Bottle for testing in the neonatal intensive care unit (NICU) and for commercialization. Funded with Phase I and Phase II SBIR awards from the NIH, the project team has completed development and testing of a preliminary design and prototype. This prototype is currently being tested in the NICU at Children's Hospital and Beth Israel Deaconess Medical Center.
Intellectual property around the Active Bottle is covered by U.S. Patent 6,033,367 and a more recent U.S. application 11/575,602 was filed in March of 2007.
Beating Heart Cardiac Surgery Instruments:
(Pedro del Nido, MD, Cardiovascular Surgery)
Dr. Pedro del Nido, chief of Cardiac Surgery, and his colleagues at Children's Hospital Boston are developing surgical instruments to enable beating heart surgical repair of septal defects and mitral valve prolapse. These specialized devices will enable minimally invasive repairs inside the beating heart that are not possible with the current minimally invasive techniques and transcatheter procedures. The specialized instruments in development are:
- A cardioport that permits the safe introduction of surgical instruments into the cardiac chambers without the risk of significant blood loss or air emboli. It also provides optical visualization in the presence of blood. Initial prototyping has been done with funding from MTTC and CIMIT. The prototype has been tested in a porcine model.
- A deployment system for the introduction of bioprosthetic and synthetic patches to repair septal defects. The deployment system, developed with funding from the NIH, successfully delivers a polyester patch to close atrial and ventricular septal defects created in porcine septa.
- A fixation anchor with a customized delivery device to attach a patch to the septum once the patch has been delivered by the deployment system. Prototyping and animal testing have been funded by the NIH. Studies have demonstrated that the fixation anchor successfully penetrates the patch material and septum to hold the patch in place.
- A mitral clip with a customized delivery device for the treatment of mitral valve prolapse. Prototyping and testing have been done with funding from the NIH.