The Michael R Freeman Innovation Award Competition

The Michael R Freeman Innovation Award Competition

About the Award
In collaboration with the Heart and Stroke/Richard Lewar Centre of Excellence in Cardiovascular Research (HSRLCE), the academic/teaching hospitals from the Toronto Central Local Health Integration Network (i.e. The Hospital for Sick Children, St. Michael’s Hospital, Sunnybrook Health Sciences Centre, University Health Network, and Women’s College Hospital) hosted a Cardiac and Vascular Collaborative Innovation Competition. The goal is to spur innovation and collaboration between institutes with the aim of improving quality of care within cardiac and vascular programs. The purpose of the award is to provide seed funding for novel ideas aimed at cardiovascular disease management, emphasizing collaborative research and development at multiple sites within the TCLHIN and initiated by at least one investigator from within the LHIN. Priority will be given to ideas with a pathway toward commercialization within 5 years.

Funding Source/Details:
Each of the five participating sites (SickKids, SMH, SHSC, UHN & WCH) commit funds of $35,000 per site toward associated activities at their site. This is matched by a $75,000 support by HSRLCE, to provide a total award pool of $250K per year. The total funding available per year is $250,000. The maximum award per successful proposal is $150,000.

2018 RECIPIENTS:

Dr. Paul Dorian, Director, Division of Cardiology at St. Michael’s Hospital was awarded first place for the 2018 Dr. Michael R. Freeman Innovation Award in the amount of $115,000.

Co-Applicants: 
Paul Angaran, MD, Division of Cardiology, St Michael’s Hospital
Sheldon Cheskes, MD, Medical Director, Regions of Halton and Peel EMS, Sunnybrook Centre for Prehospital Medicine

Innovation Title
The “AED on the way” project: Getting automated external defibrillators to the scene of cardiac arrest

About the Innovation
Sudden cardiac death is common and survival rates are poor. Bystanders can save a life by applying a defibrillating shock through an automated external defibrillator (AED). AEDs are effective and lifesaving if applied quickly after collapse, with survival rates increasing from 10-15% without an AED to 40-50% if an AED is used effectively. Unfortunately, they are seldom used because bystanders cannot locate or retrieve the AED quickly enough. Even if bystanders know that an AED is required, locating and retrieving the AED is challenging.

Our invention is a product: it is a small portable attachment to an AED that “advertises itself’ and asks that the AED to be transported to the side of the victim. It is called “AED on the way”. 911 Dispatchers will remotely activate the device, which will visually and audibly announce itself to bystanders, and provide them with instructions, including a map, and ask to be transported to the side of the victim, whose location is known, The invention will work with any AED from any manufacturer. This will result in a substantial increase in the timely use of AEDs, a known life-saving technology.

————————————————————————————————————————————————

Dr. Robert Hamilton, Professor and Senior Associate Scientist at The Hospital for Sick Children has been awarded second place for the 2018 Dr. Michael R. Freeman Innovation Award in the amount of $112,500.

Co-Applicants:
Danna Spears, Clinical Director, Heritable Arrhythmia Program, University Health Network
Paul Dorian, Professor of Medicine and Department Director, Division of Cardiology, University of Toronto and St Michael’s Hospital

Innovation Title
Validation and application of a biomarker identifying arrhythmogenic right ventricular cardiomyopathy

About the Innovation

We have identified an excellent biomarker for Arrhythmogenic right ventricular cardiomyopathy (ARVC), a serious heart condition that causes sudden cardiac death in adolescents and young adults that has up until now been very difficult to diagnose.

ARVC is an inherited arrhythmia condition that begins to manifest just prior to adolescence, with mortality peaking at age 35 years, and thus is an excellent opportunity for collaboration between pediatric and adult cardiology. It contributes substantially to life-years lost from sudden cardiac death (SCD), yet is difficult to diagnose either clinically or genetically (gene-elusive in over half of cases). We noted that both ARVC and certain skin blistering diseases are disorders of desmosomes. While ARVC is a genetic desmosomal disease, skin blistering diseases can be caused either by genetic mutations of desmosomes or antibodies to them. We therefore investigated whether antibodies might also contribute to ARVC, and were astounded to find a specific autoantibody to the desmosomal protein Desmoglein-2 (anti-DSG2 Ab) was present in every case of definite ARVC (based on accepted 2010 ARVC Task Force criteria), no matter whether an ARVC gene mutation was identified, nor which mutation was present. Anti-DSG2 Ab was confirmed in an independent cohort, was absent in two sets of control sera, and absent in both hypertrophic and dilated cardiomyopathies. As an additional validation, anti-DSG2 Ab also identified all ARVC-affected Boxer dogs (a naturally occurring animal model of this disease) and was negative in healthy Boxer dogs whose pedigrees were free of ARVC.

We developed an enzyme-linked immune-sorbent assay (ELISA) measuring antibodies to DSG2 protein, and assessed our combined cohorts of borderline and definite ARVC (45 subjects) compared to combined normal control cohorts (32 controls). A receiver operator characteristic (ROC) curve identifies an ELISA optical density (O.D.) of 0.1060 as the best cut-point, with a sensitivity of 98%, specificity of 97% and an area under the curve of 0.99. Thus our test is an excellent marker for ARVC.

The level of antibody correlates with arrhythmia burden as a measure of disease activity. Since heterozygous ARVC mutations result in anti-DSG2 Ab against all desmosomes (mutated or wild-type), the result is a dominant negative effect. ARVC gene discovery is difficult due to incomplete penetrance and variable expression of disease. If anti-DSG2 Ab can identify pre-clinical disease, antibody status will also provide a quantitative trait for segregation analysis in gene-elusive families, providing for new gene discovery.

Our discovery of anti-DSG2 Ab in ARVC has received intellectual protection, but requires further development and assessment in a larger cohort of subjects, including those with earlier and pre-clinical stages of disease, before being ready for commercialization.

Liz ThuoThe Michael R Freeman Innovation Award Competition