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 Deep Brain Stimulation Provides Sustained Relief for Severe Depression
19.03.2019 | Universitätsklinikum Freiburg

nachricht AI study of risk factors in type 1 diabetes
06.03.2019 | University of Gothenburg

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 taming of the light screw

DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.

The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...

Im Focus: Magnetic micro-boats

Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.

The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...

Im Focus: Self-healing coating made of corn starch makes small scratches disappear through heat

Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.

Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...

Im Focus: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

Im Focus: Heading towards a tsunami of light

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.

"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Solving the efficiency of Gram-negative bacteria

22.03.2019 | Life Sciences

Bacteria bide their time when antibiotics attack

22.03.2019 | Life Sciences

Open source software helps researchers extract key insights from huge sensor datasets

22.03.2019 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>