Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Efficacy of potential therapy for autoimmune disorder of muscle weakness

08.10.2014

Nearly 60,000 Americans suffer from myasthenia gravis (MG), a non-inherited autoimmune form of muscle weakness. The disease has no cure, and the primary treatments are nonspecific immunosuppressants and inhibitors of the enzyme cholinesterase.

Now, a pair of researchers from the Perelman School of Medicine at the University of Pennsylvania have developed a fast-acting "vaccine" that can reverse the course of the disease in rats, and, they hope, in humans. Jon Lindstrom, PhD, a Trustee Professor in the department of Neuroscience led the study, published in the most recent issue of the Journal of Immunology, with senior research investigator Jie Luo, PhD.

Acetylcholine Receptor

Myasthenia gravis is caused by an autoimmune response to the acetylcholine receptor (pictured here), a muscle protein that translates nervous system signals into muscle contractions.

Credit: Drawing courtesy of Jon Lindstrom, PhD, Perelman School of Medicine, University of Pennsylvania

MG is caused by an autoimmune response to the acetylcholine receptor (AChR), a muscle protein that translates nervous system signals into muscle contractions. Autoantibodies target the part of these receptors found on the outer cell surface of muscle, leading to weakness.

Researchers can induce MG in rats by injecting the AChR protein, which produces an animal disease model called experimental autoimmune myasthenia gravis (EAMG). In this study, Lindstrom and Luo found that injecting rats with the part of the AChR found on the inside of the cell protects those animals from EAMG and reverses the course of the disease if administered after the EAMG has already been induced.

"We have an antigen-specific immunosuppressive therapy that works on the animal model and should work on human MG," says Lindstrom, adding that such therapies are "rarer than hens' teeth."

A vaccine dose of 1 mg per week for six weeks, the team found, was sufficient to block development of chronic EAMG in rats. But significantly, the vaccine also worked after induction of chronic EAMG, and could block re-induction of disease months later, as well. The vaccine appears to work by preventing synthesis of pathological antibodies to the extracellular surface of the AChR protein.

Although called a "vaccine," Lindstrom's therapeutic is not like a vaccine for influenza or measles. In those cases, the idea is to raise immunity to disease antigens that can then attack the pathogen should it infect the body in the future. In the case of MG, the vaccine targets immune cells that recognize and target a self protein – the acetylcholine receptor, which helps transmit neural signals from cell to cell – and marks them for death.

"We are trying to modulate a deviant immune response," Lindstrom explains.

The trick here is that the vaccine is made not from the portion of the AChR protein that the immune system normally would see – that part that is exposed on the outer surface of cells. Instead, it is built using the protein's cytoplasmic, or inner, cell regions. This formulation induces a robust, antigen-specific suppression of the immune response without also inducing MG itself. This may involve inhibition of cells involved in making pathological antibodies and regulating that response, but the exact mechanisms have not yet been determined.

Lindstrom's lab first described the vaccine itself in a 2010 publication in the Annals of Neurology. But this earlier work didn't try to block or treat chronic disease, and injected the vaccine without the use of a chemical cocktail that amplifies the resulting immune response, called an adjuvant. The present study suggests that pairing the vaccine with an adjuvant is safe – that is, it doesn't cause MG – and effective.

Now, says Lindstrom, the goal is to test this approach in animals with EAMG and MG using other human adjuvants and then move to human clinical trials.

###

The research was funded by the Muscular Dystrophy Association.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 17 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2013 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2013, Penn Medicine provided $814 million to benefit our community.

Karen Kreeger | Eurek Alert!
Further information:
http://www.uphs.upenn.edu/news/

More articles from Health and Medicine:

nachricht On track to heal leukaemia
18.01.2017 | Universitätsspital Bern

nachricht Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>