Genetic material offers potential SARS treatment
Monday, August 22nd 2005, 10:01 am
By: News On 6
WASHINGTON (AP) _ Small fragments of genetic material that can silence specific genes are showing promise in battling the deadly severe acute respiratory syndrome.
SARS, first recognized in 2002, killed 774 people worldwide before it was brought under control by quarantine, isolating patients and restricting travel.
Since then, researchers have struggled to find a treatment or vaccine before a new outbreak occurs.
Researchers reported Sunday that snippets called interfering RNA can reduce an existing infection in monkeys and help protect them from new ones.
RNA, or ribonucleic acid, transmits information from the DNA that carries the blueprint of life in cells. The small fragments, called siRNA, can be tailored to silence specific genes. Scientists are investigating this use of RNA in hopes it can help with a variety of medical conditions.
A team led by Patrick Y. Lu of Intradigm Corp. in Rockville, Md., said in the online edition of the journal Nature Medicine that researchers in China and the United States tested two types of siRNA that target different parts of the genome of the SARS virus.
They used five groups, each with four monkeys _ specifically, macaques.
Two were control groups that did not receive treatment. Of the three other groups, one was treated with siRNA before being exposed to SARS; the second was treated at the same time as exposure to the disease; the third got the siRNA following infection.
Both the SARS virus and the siRNA were delivered by nasal sprays.
All the infected animals developed some symptoms. But there was much less lung damage in the animals treated with the RNA fragments, and their body temperature increases were smaller.
A characteristic of SARS is severe, often fatal, damage to the tiny air sacs in the lungs that exchange oxygen for carbon dioxide. Severe damage to those sacs was found in the control animals, while injury in the treated macaques was relatively mild, the researchers said.
Throat samples taken four days after infection found evidence of the SARS virus in just 25 percent of the animals treated with siRNA.
The monkeys that got siRNA before infection had the fewest symptoms, the smallest increase in body temperature and the least lung damage.
Just how the treatment deals with SARS remains to be determined.
Scientists said the siRNA may block the virus from infecting cells, it may prevent the virus from making damaging proteins after it enters cells or it may prevent the virus from reproducing.
Dr. Rajnish S. Dave of Thomas Jefferson University Medical College in Philadelphia said the study is significant for all siRNA-based treatment of viruses. It's also a step closer to translating these technologies to regular use.
Dave said, however, the use of siRNA-based technologies is limited in fighting respiratory viruses.
Dr. Krishan K. Pandey of the University of Minnesota said other studies involving siRNA have produced good results in mice.
``The unique point of this report is the usage of ... macaques, which is surely closer to humans than mice, and also that the study is aimed toward a very recently identified virus SARS,'' Pandey said.
``Another strong point of this study is the successful use of siRNA in prophylactic treatment of SARS, which is surely a great thing if it is successful in humans,'' Pandey said.
He said the move to human trials will involve different challenges.
Neither Pandey nor Dave was part of Lu's research team.
Several of the team authors, including Lu, disclosed being either consultants for or employees of Intradigm or Top Genomics, Ltd., of Guangzhou, China. Both biopharmaceutical companies are developing RNA therapies for the treatment of human disease.
Additional financial support for the research came from agencies of the Guangzhou provincial government and the China World Trade Corporation.
In a separate Nature Medicine report, also published online on Sunday, researchers said they had found an experimental vaccine that can prime the immune system to help fight an aggressive form of lymphoma.
That study was done by scientists at The University of Texas M. D. Anderson Cancer Center and the National Cancer Institute.
Many scientists have thought two types of immune cell produced in the bone marrow _ B cells and T cells _ are needed to prime the immune system.
The cancer researchers found that after a treatment that depletes B cells, they could follow with an experimental vaccine that boosts T-cell immune response. The treatment produced an 89 percent survival rate at 46 months in 26 patients with mantle cell lymphoma, which is difficult to control.
``This paves the way to use vaccines in a number of hematological cancers that are treated by eliminating diseased B cells,'' Dr. Sattva Neelapu, lead author of the study, said in a statement.