Researchers from Singapore and the United States are focused on a novel drug candidate with marine origins as a new method to prevent or treat vision loss.
SINGAPORE, 08 AUGUST 2019 – Researchers from Singapore and the United States are focused on a novel drug candidate with marine origins as a new method to prevent or treat vision loss.
According to the Singapore National Eye Centre, Singapore’s population is uniquely vulnerable to eye diseases and disorders at every life stage, and the risk of blindness increases fifteen-fold for Singaporeans aged 50 to 80 and above[1][1]. Abnormal blood vessel formation is a defining feature of many eye diseases, including neovascular age-related macular degeneration, neovascular glaucoma and advanced diabetic retinopathy. A protein called vascular endothelial growth factor, or VEGF, was previously identified as a key regulator of new blood vessel formation in health and diseases.
“Therapies that inhibit VEGF have revolutionised the treatment of many retinal diseases, such as age-related macular degeneration and diabetic retinopathy, over the last decade,” said Tien Y Wong, M.D., Ph.D., a professor and chair of ophthalmology at the Singapore National Eye Centre and Singapore Eye Research Institute, or SERI. “Despite this progress, for some of these diseases, up to 30-40% of patients do not respond to treatment, may develop resistance over time or require long-term maintenance therapy.”
University of Florida (UF) College of Pharmacy researchers teamed with collaborators at SERI and at A*STAR’s Institute of Molecular and Cell Biology (IMCB) in Singapore, to see whether Apratoxin S4, a novel molecule based on marine cyanobacteria, could be an effective therapy in restricting abnormal blood vessel formation in the eye, which may be a potential treatment for these retinal diseases in the future.
Apratoxin S4 originates from a family of molecules known as apratoxins, which are found in select areas of the world’s oceans. Years of medicinal chemistry refinements have yielded several potential cancer therapies from apratoxins, and scientists are beginning to explore the molecule’s potential in treating other health conditions, such as eye diseases.
The research team discovered in laboratory testing that Apratoxin S4 inhibited the development of abnormal blood vessels in the eye but left normal blood vessel formation untouched. They found multiple methods of delivering the therapy proved effective, including systemic drug delivery into the bloodstream or local drug delivery into the back of the eye. Finally, they determined Apratoxin S4 can be an effective therapy on its own, or work in combination with VEGF-inhibiting drugs to stop the growth of abnormal blood vessels.
“Apratoxin S4 could potentially address the resistance problem to standard-of-care VEGF therapy by inhibiting multiple new blood vessel forming pathways,” said Hendrik Luesch, Ph.D., a professor and chair of medicinal chemistry and the Debbie and Sylvia DeSantis Chair in Natural Products Drug Discovery and Development in the University of Florida’s College of Pharmacy. “Our colleagues in Singapore showed in various models the efficacy and potency of the compound,” he said, “and it acts through a mechanism that is distinct, yet partially overlapping, with VEGF therapy. This is consistent with our original hypothesis based on years of studying the mechanism of action.”
Xiaomeng Wang, Ph.D., an Associate Professor at the Lee Kong Chian School of Medicine, Nanyang Technological University Singapore and A*STAR’s IMCB, led the biological studies. “Angiogenesis is a complex process involving coordinated interactions between different types of cells,” Wang said. “Pericyte-covered vessels are believed to be protected from anti-VEGF drugs. Apratoxin S4 has unique features in that it affects the signalling and function of retinal microvascular endothelial cells and pericytes, which is likely to be more effective than drugs targeting a single type of vascular cells.”
Professor Wanjin Hong, Ph.D., Executive Director of A*STAR’s IMCB, noted the growing need for treatment options for eye diseases. “The burden of eye diseases in Singapore is expected to increase in the future, with the population being vulnerable at every stage of life,” he said. “Therefore, an urgent need exists to develop such novel approaches to addressing vision loss for those afflicted or at risk.”
UF’s Luesch said researchers increasingly are looking for answers to vexing questions in every corner of the globe, including under the sea. “The biodiversity of organisms in the world’s oceans offers vast potential for discovering promising drug candidates from cyanobacteria and other sources,” he said. “The apratoxin family of molecules have produced another novel drug candidate that has the potential to treat eye diseases and improve the eyesight for many people around the world struggling with vision loss.”
The worldwide commercial rights to the apratoxin family of molecules are exclusively licensed to Oceanyx Pharmaceuticals Inc., a novel drug discovery and development company that leverages marine biology-based, natural product research.
The study, “Apratoxin S4 inspired by a marine natural product, a new treatment option for ocular angiogenic diseases” was published in the journal Investigative Ophthalmology & Visual Science — an online journal published by the Association for Research in Vision and Ophthalmology. It was supported by the SERI-IMCB Programme In Retinal Angiogenic Diseases (SIPRAD) and Oceanyx Pharmaceuticals Inc.
Link to online version:
https://iovs.arvojournals.org/
The vision of Institute of Molecular and Cell Biology (IMCB) is to be a premier cell and molecular biology institute which addresses the mechanistic basis of human diseases and its mission is to conduct cutting-edge discovery research in disease pathways; to groom early career researchers to be future leaders in research; and to collaborate with medical and industry communities for research impact. IMCB plays an important role training and recruiting scientific talents, and has contributed to the development of other research entities in Singapore. Its success in fostering a biomedical research culture in Singapore has catalysed Singapore’s transformation into an international hub for biomedical research, development and innovation.
Funded by A*STAR, IMCB’s Discovery research comprises 5 major programmes: Cancer Cell Signalling, Multi-Modal Molecular (M3) Biology, Epigenetics and Diseases, iPS cell and Regenerative Medicine, and Technology and Translation. IMCB’s technologies and platforms focus on Genome-wide RNAi, Humanised Mouse Models, Proteomics and Protein Engineering, Gene Therapy and Gene Editing, and Molecular Histopathology.
For more information about IMCB, please visit www.imcb.a-star.edu.sg.
About the Agency for Science, Technology and Research (A*STAR)
The Agency for Science, Technology and Research (A*STAR) is Singapore’s lead public sector agency that spearheads economic oriented research to advance scientific discovery and develop innovative technology. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit society.
As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by contributing to societal benefits such as improving outcomes in healthcare, urban living, and sustainability.
We play a key role in nurturing and developing a diversity of talent and leaders in our Agency and research entities, the wider research community and industry. A*STAR’s R&D activities span biomedical sciences and physical sciences and engineering, with research entities primarily located in Biopolis and Fusionopolis. For ongoing news, visit www.a-star.edu.sg.
About Singapore Eye Research Institute (SERI)
Established in 1997, SERI is Singapore’s national research institute for ophthalmic and vision research and is the research centre of the Singapore National Eye Centre. With a mission to conduct high-impact eye research that prevents blindness, low vision and major eye diseases common to Singapore and Asia, SERI has over the years, conducted landmark research projects that have led to tangible outcomes, patient benefits and success stories. The research conducted has translated into effective clinical care and better outcomes for patients suffering from conditions such as corneal diseases, myopia, age-related macular degeneration and glaucoma. The institute is also at the forefront of developing natural anti-microbial drugs that will see potential benefit going beyond treating eye conditions.
With a faculty of more than 196 staff, encompassing clinician scientists, scientists, research fellows, PhD students and support staff, SERI is the largest eye research institute in the Asia Pacific region. With direct affiliations to and several adjunct faculties from various eye departments, medical schools, biomedical institutes and tertiary centres, it undertakes vision research in collaboration with local as well as major eye centres and research institutes throughout the world. SERI ranks first globally in terms of eye publications per capita, far ahead of several developed countries.
For more insights into the institute, visit www.snec.com.sg/research-
[1][1] Source: Singapore National Eye Centre https://www.snec.com.sg/
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