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!
The first genome of a coral reef fish
29.09.2016 | King Abdullah University of Science and Technology
New switch decides between genome repair and death of cells
27.09.2016 | University of Cologne - Universität zu Köln
Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of light metals.
Scientists at the University of Stuttgart have now developed two new process variants that will considerably expand the areas of application for friction stir welding.
Technologie-Lizenz-Büro (TLB) GmbH supports the University of Stuttgart in patenting and marketing its innovations.
Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of...
Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.
Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...
The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.
“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...
With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.
Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...
For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.
Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...
29.09.2016 | Event News
28.09.2016 | Event News
27.09.2016 | Event News
29.09.2016 | Materials Sciences
29.09.2016 | Materials Sciences
29.09.2016 | Interdisciplinary Research