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!
Fish Oil-Diet Benefits May be Mediated by Gut Microbes
28.08.2015 | University of Gothenburg
Bio-fabrication of Artificial Blood Vessels with Laser Light
28.08.2015 | Fraunhofer-Institut für Lasertechnik ILT
A University of Oklahoma astrophysicist and his Chinese collaborator have found two supermassive black holes in Markarian 231, the nearest quasar to Earth, using observations from NASA's Hubble Space Telescope.
The discovery of two supermassive black holes--one larger one and a second, smaller one--are evidence of a binary black hole and suggests that supermassive...
A team of European researchers have developed a model to simulate the impact of tsunamis generated by earthquakes and applied it to the Eastern Mediterranean. The results show how tsunami waves could hit and inundate coastal areas in southern Italy and Greece. The study is published today (27 August) in Ocean Science, an open access journal of the European Geosciences Union (EGU).
Though not as frequent as in the Pacific and Indian oceans, tsunamis also occur in the Mediterranean, mainly due to earthquakes generated when the African...
In mountainous regions earthquakes often cause strong landslides, which can be exacerbated by heavy rain. However, after an initial increase, the frequency of these mass wasting events, often enormous and dangerous, declines, in fact independently of meteorological events and aftershocks.
These new findings are presented by a German-Franco-Japanese team of geoscientists in the current issue of the journal Geology, under the lead of the GFZ...
Bacteria do not cease to amaze us with their survival strategies. A research team from the University of Basel's Biozentrum has now discovered how bacteria enter a sleep mode using a so-called FIC toxin. In the current issue of “Cell Reports”, the scientists describe the mechanism of action and also explain why their discovery provides new insights into the evolution of pathogens.
For many poisons there are antidotes which neutralize their toxic effect. Toxin-antitoxin systems in bacteria work in a similar manner: As long as a cell...
It comes when called, bringing care utensils with it and recording how they are used: Fraunhofer IPA is developing an intelligent care cart that provides care staff with physical and informational support in their day-to-day work. The scientists at Fraunhofer IPA have now completed a first prototype. In doing so, they are continuing in their efforts to improve working conditions in the care sector and are developing solutions designed to address the challenges of demographic change.
Technical assistance systems can improve the difficult working conditions in residential nursing homes and hospitals by helping the staff in their work and...
20.08.2015 | Event News
20.08.2015 | Event News
19.08.2015 | Event News
31.08.2015 | Earth Sciences
28.08.2015 | Physics and Astronomy
28.08.2015 | Health and Medicine