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 The personality factor: How to foster the sharing of research data
06.09.2017 | ZBW – Leibniz-Informationszentrum Wirtschaft

nachricht Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung

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: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>