Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Novel proteins designed that block inflammation regulator associated with rheumatoid arthritis

26.09.2003


Researchers at UT Southwestern Medical Center at Dallas have tested and validated novel proteins, created by California-based Xencor, that block activity of a major molecule involved in the onset of inflammation, an innovation that may translate into new therapeutic options for people with rheumatoid arthritis.



Researchers at both institutions report in today’s issue of Science that blocking the activation of a regulator of inflammation called tumor necrosis factor (TNF) decreased swelling by 25 percent in a rodent model of the human disease rheumatoid arthritis. Elevated TNF levels are associated with the onset of rheumatoid arthritis.

The uniqueness of the new inhibitors, the scientific team reports, lies in their design and mode of action. Unlike the drugs that are currently available, the structure and sequence of these newly designed molecules are similar to naturally produced proteins, making it less likely that the body will elicit an immune response to fight off foreign agents.


"What we’ve engineered are variant proteins that are very similar to the protein that the body expresses on its own, which makes it less likely that the body will see it as foreign," said Dr. Malú Tansey, a lead author of the study and assistant professor of physiology at UT Southwestern, where some of the in vivo testing and validation was completed and where work will continue on these TNF inhibitors.

"The inhibitors are actually modified versions of the TNF protein that is naturally found in the body, but with a few mutations that prevent them from binding to receptors but still allow the proteins to bind TNF. The end result is sequestration of active TNF away from the receptors that mediate inflammatory responses implicated in rheumatoid arthritis and several other autoimmune diseases," said Dr. Tansey, former member of the Xencor team.

These findings provide a "promising new avenue" for physicians who treat the 2.1 million Americans with rheumatoid arthritis, said Dr. David Karp, chief of rheumatic diseases and associate director of the Harold C. Simmons Arthritis Research Center.

"This is a very novel approach; one that has not been looked at by other investigators," he said. "This family of proteins is not only implicated in the painful inflammation of rheumatoid arthritis, but also the joint destruction that accompanies the disease. These proteins also may be critical for other autoimmune diseases like multiple sclerosis and systemic lupus erythematosis."

Rheumatoid arthritis is an autoimmune disease in which the body’s immune system attacks its own tissues, mistaking them for foreign substances like bacteria or viruses. This disease is characterized by redness, swelling, loss of joint function and deterioration of cartilage and bone in the joints.

There is no cure for the disease, but there are currently three drugs that specifically target TNF inhibition. Although these drugs have been shown to be effective in decreasing the pain associated with the disease and in some cases joint destruction, some patients develop antibodies against the drugs, which may require the administration of higher doses.

"This side effect may lower the effectiveness of these drugs," Dr. Tansey said. "Our prediction is that because these TNF variants are virtually identical to native TNF, the body will not form antibodies against them, but this will have to be tested."

The TNF variants are currently in preclinical development at Xencor.

Anti-TNF therapy may also be useful in blocking inflammation in neurodegenerative diseases like Alzheimer’s and Parkinson’s disease, Dr. Tansey said.

Dr. Tansey recently received a $200,000 grant from the Michael J. Fox Foundation to examine the role that elevated levels of TNF play in the loss of dopamine-producing neurons, which lead to Parkinson’s disease.

Other researchers who contributed to this study include Sabrina Martinez, a research technician II in physiology at UT Southwestern.

The study was funded by Xencor, a private biotechnology company founded in 1997.

Amy Shields | EurekAlert!
Further information:
http://www.swmed.edu/

More articles from Studies and Analyses:

nachricht Drone vs. truck deliveries: Which create less carbon pollution?
31.05.2017 | University of Washington

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making Waves

Computer scientists use wave packet theory to develop realistic, detailed water wave simulations in real time. Their results will be presented at this year’s SIGGRAPH conference.

Think about the last time you were at a lake, river, or the ocean. Remember the ripples of the water, the waves crashing against the rocks, the wake following...

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Nanostructures taste the rainbow

29.06.2017 | Physics and Astronomy

New technique unveils 'matrix' inside tissues and tumors

29.06.2017 | Life Sciences

Cystic fibrosis alters the structure of mucus in airways

29.06.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>