Researchers halt autoimmune disease myasthenia gravis in mice
Working with mice, Johns Hopkins researchers say they have developed a gene-based therapy to stop the rodent equivalent of the autoimmune disease myasthenia gravis by specifically targeting the destructive immune response the disorder triggers in the body.
The technique, the result of more than 10 years of work, holds promise for a highly specific therapy for the progressively debilitating muscle-weakening human disorder, one that avoids the need for long-term, systemic immunosuppressant drugs that control the disease but may create unwanted side effects.
The research, if replicated in humans, could be a big leap in treating not only myasthenia gravis, but also other autoimmune disorders, the researchers say.
"To treat autoimmune diseases, we normally give drugs that suppress not only the specific antibodies and cells we want to inhibit, but that also broadly interfere with other functions of the immune system," says Daniel B. Drachman, M.D., a professor of neurology and neuroscience at the Johns Hopkins University School of Medicine and leader of the study published this month in the Journal of Neuroimmunology. "Our goal was to suppress only the abnormal response, without damaging the remainder of the immune system, and that's what we did in these mice."
A healthy immune system has the amazing ability to distinguish between the body's own cells, recognized as "self," and foreign proteins and other substances—including germs and tumors—to fight infections, cancer and other diseases. The body's immune defenses normally coexist peacefully with cells that carry distinctive "self" marker molecules. But when immune defenders encounter foreign molecules, they quickly launch an attack. Autoimmune disorders occur when the immune system makes a mistake, in which it confuses "self" with something foreign, and then launches an attack by immune cells and/or antibodies to seek out and damage the body's own cells.
Drachman, one of the world's leading authorities on myasthenia gravis and other neurologic autoimmune disorders, and his colleagues say they have found a way to create a "guided missile" approach as opposed to the "carpet bombing" of overall immunosuppression. Essentially, Drachman says, the method eliminates the cells of the immune system that are involved in the attack against self and leaves other cells alone.
The research team created the guided missiles by genetically engineering dendritic cells, which are the immune cells that specialize in presenting antigens to the immune system's T-cells. They extracted dendritic cells from mice with myasthenia gravis, purified them and inserted genes which direct these dendritic cells to target the auto-aggressive immune cells, and destroy them using a "warhead" known as Fas ligand. Then they injected back into the mice the genetically engineered cells, which homed in on the immune system's faulty T-cells. The newly introduced "guided missiles" then sought out and bound themselves to those T-cells, causing apoptosis, or cellular suicide, which halted the autoimmune attack before it could gain traction.
"This way, the autoantibodies were specifically reduced, a key step in treating myasthenia gravis," Drachman says.
The therapy dramatically reduced the autoantibodies responsible for myasthenia gravis, without affecting other responses of the immune system. However, the study was not carried out long enough to determine whether the mice were permanently cured of their disease. Theoretically, a similar approach to treatment could be translated to patients with myasthenia gravis, but so far it has not yet been tested in humans, and it is not yet known whether repeated courses of the therapy might be needed.
Myasthenia gravis, a condition found in an estimated one to seven per 10,000 people worldwide, occurs in individuals who appear to be genetically predisposed, though it is unclear exactly what triggers the disease. Overall, however, an estimated 80 to 100 known autoimmune disorders affect more than 23 million Americans.
Patients who take immunosuppressant drugs are more susceptible to infections and even some forms of cancer.
Provided by Johns Hopkins University School of Medicine
- Protein from tick saliva studied for potential myasthenia gravis treatment Mar 26, 2009 | not rated yet | 0
- Moving towards a better treatment for autoimmune diabetes Apr 09, 2012 | not rated yet | 0
- Skin sentry cells promote distinct immune responses Jul 21, 2011 | not rated yet | 0
- Immune cell death safeguards against autoimmune disease Sep 06, 2012 | not rated yet | 0
- Discovery could change the way doctors treat patients with cancer and autoimmune diseases Apr 27, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Force Between Two Concentric Solenoids
3 hours ago Imagine a finite length solenoid with outer radius R1 and inner radius R2. This solenoid has a time-varying current going though it. This solenoid is...
Synchrotron, question about insertion devices and electron velocity
3 hours ago When an electron enters an insertion device (wiggler and undulator) from the storage ring in a synchrotron the tangential velocity is equal to the...
Equating differentials => equating coefficients
4 hours ago Hi all, In thermodynamics one often has equations like A dx + B dy = ∂f/∂x dx + ∂f/∂y dy From which follows A = ∂f/∂x B = ∂f/∂y
The idea behind a reverse shock
10 hours ago So in a supernova explosion for example (5th slide) http://www.astro.princeton.edu/~burrows/classes/541/blastwavesChisari.pdf Ambient medium is...
Guass's Law for a charge distribution
10 hours ago First, this is not a homework question, just something I've been confused about for some time. I understand how to use Guass's law in many ways but...
11 hours ago Hello :) i'm new to this forum, so excuse me for my straightforwardness ;) I'm working on my bachelor work and i can't find a solution. I'm writing...
- More from Physics Forums - Classical Physics
More news stories
Kate O'Reilly's spring allergy survival kit includes the usual stuff - nasal sprays, allergy pills and a box of tissues. This season, she's added a new weapon to her line of defense: an app on her smartphone.
Immunology May 24, 2013 | not rated yet | 0
Biological processes are generally based on events at the molecular and cellular level. To understand what happens in the course of infections, diseases or normal bodily functions, scientists would need to ...
Immunology May 24, 2013 | 5 / 5 (5) | 0 |
(Medical Xpress)—Scientists at Emory Vaccine Center have shown that an immune regulatory molecule called IL-21 is needed for long-lasting antibody responses in mice against viral infections.
Immunology May 23, 2013 | 5 / 5 (2) | 0 |
Human breastmilk responds quickly to protect the child when there is an infection in mothers or babies, according to new international research led by The University of Western Australia.
Immunology May 23, 2013 | 5 / 5 (1) | 0
Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality ...
16 hours ago | 5 / 5 (2) | 5
(HealthDay)—Animals make great companions for senior citizens, but elderly people who always drive with a pet in the car are far more likely to crash than those who never drive with a pet, researchers have ...
8 hours ago | not rated yet | 1
Heart failure accelerates the aging process and brings on early andropausal syndrome (AS), according to research presented today at the Heart Failure Congress 2013. AS, also referred to as male 'menopause', was four times ...
16 hours ago | not rated yet | 1
Mortality and length of stay are highest in heart failure patients admitted in January, on Friday, and overnight, according to research presented today at the Heart Failure Congress 2013. The analysis of nearly 1 million ...
16 hours ago | not rated yet | 0
(AP)—Department of Justice lawyers have again asked a federal appeals court in New York to delay lifting age restrictions and prescription requirements on an emergency contraceptive popularly known as the morning-after ...
16 hours ago | not rated yet | 0