Bioengineering a safe treatment for retinopathy, the leading cause of vision loss in Canada
A new drug approach has been developed for safer clean-up of deformed blood vessels in the eye by a research team at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital in Toronto.
The growth of malformed blood vessels that can burst is a leading cause of vision loss in North America. Retinopathy and retina degeneration are associated with premature birth, with diabetes, and with increasing age.
Research just published by Dr. Andras Nagy and co-authors shows both safety and effectiveness in their bioengineered compound when treating retinopathy in mice. The therapeutic, which they called "Sticky-trap," shuts down tiny deformed blood vessels in the eye without affecting healthy vessels in other sites of the body.
The research appears in EMBO Molecular Medicine, which published a separate editorial stating that the compound "holds great promise as a strategy that could be rapidly translated into clinical practice. […] We expect that Sticky-trap and future related molecules will have significant impact on the field of tumour biology in local control of recurrent disease. […]"
Dr. Nagy is a Senior Investigator at the Lunenfeld-Tanenbaum and holds a Canada Research Chair in Stem Cells and Regeneration. He is a Professor in the Department of Obstetrics and Gynacology at University of Toronto and an Investigator at the McEwen Centre for Regenerative Medicine. Co-authors include colleagues from University of California Los Angeles, The Scripps Research Institute (La Jolla CA), University of Toronto, and the Lunenfeld-Tanenbaum.
Selective action is key to safety
Like some other treatments for retinopathy, Sticky-trap is injected into the eye. The potential game-changer is Sticky-trap's safety profile. It is stable and long-lasting once in the eye. If the compound gets into the circulation, it quickly inactivates – ensuring that it does not affect other blood vessels, tissues, and organs.
A problem in this research arena – called antiangiogenesis – has been finding a compound that is selective, closing off abnormal blood vessels only in the diseased organ while leaving all others intact. "That's difficult, and it's what makes this research high-risk as well as high-impact," Dr. Nagy says.
Type 2 diabetes illustrates the challenge. "Patients with diabetic retinopathy are losing vision because blood vessels in their eyes overgrow, become deformed and burst, often tearing the retina in the process. Drugs that suppress the excess vessel formation in the eye could negatively affect healthy organs if they escape into the blood, causing kidney function problems, poor wound healing, and hypertension," Dr. Nagy adds. These side effects are serious health threats that the Sticky-trap approach can avoid.
Over the nine years it took to bring the project to fruition, Dr. Nagy's team used cutting-edge genetic and pharmacological techniques to engineer the new two-step biologics. Sticky-trap includes a binding component that attaches to the surface of cells, ensuring that it remains in place and is stable, as well as the biologically active component. "That's important when a treatment involves injection directly into a diseased tissue," says first author Dr. Iacovos Michael, a post-doctoral fellow in the Nagy lab. "The longer-acting it is, the fewer injections a patient will need." He adds that the project "is just the beginning for the establishment of a new class of pharmacological entity, 'sticky' biologics, characterized by localized, targeted activity. The same principle could be used to develop similar local-acting biologics for other conditions such as inflammatory and autoimmune diseases."
Dr. Nagy is renowned for his work in stem cells, blood vessel biology, and creating genetic tools in cancer cells, among other areas. His team is also working on applications of the two step Sticky-trap for solid tumours.
Upon publication on May 6, Sticky-trap became available to biotech and pharmaceutical companies to adapt and develop.
"The significant advance in this approach is its built-in precision guidance system," says Dr. Jim Woodgett, Director of the Lunenfeld-Tanenbaum. "Worldwide research efforts have developed powerful agents that can treat diseased tissues but if they cannot be steered to where they are needed, they can also cause collateral damage. The initial application to diabetic retinopathy shows proof-of-principle in a very important disease, but the approach can be adapted to other powerful drugs and diseases where localized activity is needed."
The research paper is "Local acting Sticky-trap inhibits vascular endothelial growth factor dependent pathological angiogenesis in the eye," on-line May 6 2014 in EMBO Molecular Medicine. Funding was supported by the Canadian Institutes for Health Research, McEwen Centre for Regenerative Medicine, Robert and Sheryl McEwen, Canadian Cancer Society Research Institute, Mount Sinai Hospital Foundation, National Eye Institute, and Lowy Medical Research Institute.
Lunenfeld-Tanenbaum Research Institute
Mount Sinai Hospital
(416) 586-4800 #2046
Polly Thompson | Eurek Alert!
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration
"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...
Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.
Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
16.01.2017 | Power and Electrical Engineering
16.01.2017 | Information Technology
16.01.2017 | Power and Electrical Engineering