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 Statistical method developed at TU Dresden allows the detection of higher order dependencies
07.02.2020 | Technische Universität Dresden

nachricht Novel study underscores microbial individuality
13.12.2019 | Bigelow Laboratory for Ocean Sciences

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: High-pressure scientists in Bayreuth discover promising material for information technology

Researchers at the University of Bayreuth have discovered an unusual material: When cooled down to two degrees Celsius, its crystal structure and electronic properties change abruptly and significantly. In this new state, the distances between iron atoms can be tailored with the help of light beams. This opens up intriguing possibilities for application in the field of information technology. The scientists have presented their discovery in the journal "Angewandte Chemie - International Edition". The new findings are the result of close cooperation with partnering facilities in Augsburg, Dresden, Hamburg, and Moscow.

The material is an unusual form of iron oxide with the formula Fe₅O₆. The researchers produced it at a pressure of 15 gigapascals in a high-pressure laboratory...

Im Focus: From China to the South Pole: Joining forces to solve the neutrino mass puzzle

Study by Mainz physicists indicates that the next generation of neutrino experiments may well find the answer to one of the most pressing issues in neutrino physics

Among the most exciting challenges in modern physics is the identification of the neutrino mass ordering. Physicists from the Cluster of Excellence PRISMA+ at...

Im Focus: Therapies without drugs

Fraunhofer researchers are investigating the potential of microimplants to stimulate nerve cells and treat chronic conditions like asthma, diabetes, or Parkinson’s disease. Find out what makes this form of treatment so appealing and which challenges the researchers still have to master.

A study by the Robert Koch Institute has found that one in four women will suffer from weak bladders at some point in their lives. Treatments of this condition...

Im Focus: A step towards controlling spin-dependent petahertz electronics by material defects

The operational speed of semiconductors in various electronic and optoelectronic devices is limited to several gigahertz (a billion oscillations per second). This constrains the upper limit of the operational speed of computing. Now researchers from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and the Indian Institute of Technology in Bombay have explained how these processes can be sped up through the use of light waves and defected solid materials.

Light waves perform several hundred trillion oscillations per second. Hence, it is natural to envision employing light oscillations to drive the electronic...

Im Focus: Freiburg researcher investigate the origins of surface texture

Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.

Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

70th Lindau Nobel Laureate Meeting: Around 70 Laureates set to meet with young scientists from approx. 100 countries

12.02.2020 | Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

 
Latest News

Turbomachine expander offers efficient, safe strategy for heating, cooling

25.02.2020 | Power and Electrical Engineering

The seismicity of Mars

25.02.2020 | Earth Sciences

Cancer cachexia: Extracellular ligand helps to prevent muscle loss

25.02.2020 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>