Researchers at SGH and Duke-NUS a step closer to finding treatment for dengue fever

There have been several news reports that the world's first dengue vaccine will be available next year. However, the latest clinical trials show that the vaccine only provides a protection of around 50 per cent for DENV-2 and DENV-1, which are commonly found in Singapore.

DENV-1 accounts for 90 per cent of infections locally as a large population lacks the immunity against this particular dengue virus serotype. Until a vaccine that can offer higher protection becomes available, it is crucial to find a suitable treatment for dengue fever, as there is presently none available world-wide.

The good news is that a team of Singapore General Hospital (SGH) and Duke-NUS Graduate Medical School (Duke-NUS) researchers are now a step closer to finding a treatment for dengue fever. In the CELADEN study completed last year, the team found that Celgosivir, a medicine derived from a naturally occurring compound found in the seeds of the Moreton Bay Chestnut tree, is generally safe and well-tolerated by patients affected with the dengue virus.

Participants recruited for the study were admitted to SGH for five days, during which time they received either the placebo or Celgosivir. They continued to be followed up on days 7, 10 and 15 at the outpatient clinics where clinical histories and blood were taken. A physical examination of the patient was also done during these sessions.

"We found that the drug regimen in our CELADEN study was well-tolerated. And because dengue virus is cleared from the blood within three to five days and fever subsides in the same period, a regimen with more frequent dosing will be tested in the next phase of our trial to see its therapeutic effect," said Dr Jenny Low, Senior Consultant, Department of Infectious Diseases, SGH, and Principal Investigator of the study.

"Prior work conducted at Duke-NUS has demonstrated that dose regimen is an important factor in mediating the antiviral effects of Celgosivir," said Professor Subhash Vasudevan, Emerging Infectious Diseases Program at Duke-NUS.

The findings of the study were published in Lancet Infectious Diseases, a world-leading peer-reviewed scientific medical journal, on 28 May 2014.

Moving to the next phase of the study, SingHealth and Duke-NUS have signed an exclusive licensing agreement with 60 Degrees Pharmaceuticals to evaluate the efficacy and safety of an alternate dosing regimen as well as combination drug treatments in dengue patients. The NUS Industry Liaison Office, which is part of NUS Enterprise, took the lead in coordinating and facilitating this multi-party collaboration and the license negotiation.

"Other viral diseases such as hepatitis C and HIV required combination regimens to demonstrate clinical benefit. This may also be the case for dengue. To that end, 60P has also entered into a collaboration agreement with NUS earlier in March 2014 to investigate the utility of drug combinations in animal models. This agreement builds on prior collaborations between the parties to evaluate the antiviral effects of other approved drugs," said Mr Geoff Dow, CEO, 60P.

Dengue fever is an acute febrile illness transmitted by mosquitoes, which affects half the world's population. There are 96 million symptomatic infections, 500,0000 hospitalisations and 25,000 deaths per year attributed to the disease. The economic burden is $12 billion. In Singapore, as elsewhere, the incidence of the disease has continued to increase despite aggressive control measures.

Singapore General Hospital, a member of Singapore Health Services, is the public sector's flagship hospital. Established in 1821, SGH is Singapore's largest acute tertiary hospital with 1,700 beds and national referral centre offering a comprehensive range of 36 clinical specialties on its campus. Every year, about 1 million Singaporeans benefit from advanced medical care delivered by its 800 specialists. As an academic healthcare institution and the bedrock of medical education, SGH plays a key role in nurturing doctors, nurses and allied health professionals, and is committed to innovative translational and clinical research in her continual strive to provide the best care and outcomes to her patients.

http://www.sgh.com.sg

The Duke-NUS Graduate Medical School Singapore (Duke-NUS) was established in 2005 as a strategic collaboration between the Duke University School of Medicine, located in North Carolina, USA and the National University of Singapore (NUS). Duke-NUS offers a graduate entry, 4-year M.D. (Doctor of Medicine) training program based on the unique Duke model of education, with one year dedicated to independent study and research projects of a basic science or clinical nature. Duke-NUS also offers M.D/PhD and PhD programs. Duke-NUS has five Signature Research Programs: Cancer & Stem Cell Biology, Neuroscience and Behavioural Disorders, Emerging Infectious Diseases, Cardiovascular & Metabolic Disorders, and Health Services and Systems Research.

Duke-NUS and SingHealth, Singapore's largest public healthcare group, have established a strategic partnership in academic medicine. This initiative will guide and promote the future of medicine, tapping on and combining the collective strengths of SingHealth's clinical expertise and Duke-NUS' biomedical sciences research and medical education capabilities.

For more information, please visit http://www.duke-nus.edu.sg

60 Degrees Pharmaceuticals (60P) was founded in 2010 with a mission to discover and develop new medicines for treatment of tropical diseases. Initially 60P has focused on small molecules therapeutics for dengue fever, and plans to develop a portfolio of projects across several disease areas. The company sources intellectual property from, and collaborates with, academic and public research institutions in Singapore, Australia, the United States to commercialise new molecules with established safety profiles. 60P, together with its Singaporean and Australian collaborator, plans to initiate a Phase II study in dengue patients in 2015.

http://www.60degreespharma.com