Thursday, October 29, 2015

Why Myasthenia Gravis An Autoimmune Disorder?

Artem is a doctor of veterinary medicine and has taught science and medicine at the college level.
This lesson will go over a condition called myasthenia gravis. We’ll talk about why it occurs, how your immune system is involved, how it can be treated, if it’s curable, and what typical signs it produces in a person.
 autoimmune-disorders-2-728

Autoimmune Disease

Most every one of us has played a game called ‘monkey in the middle’, or something along those lines. It’s basically where at least one person stands in between at least two other people who throw or kick an object like a ball to one another. The role of the monkey in the middle is to block the ball from getting through to the other person. Typically, as was the case when I was the monkey in the middle, the person in the middle has a hard time intercepting the ball.
But in some cases of autoimmune diseases, diseases where your own body attacks itself, the monkey in the middle is devastatingly effective. So effective, in fact, that it causes serious problems, as this lesson will address.

What is Myasthenia Gravis?

The terrible game that our body plays with us isn’t called monkey in the middle, it’s called myasthenia gravis. This is an incurable autoimmune disease that leads a person to develop severe muscle weakness and fatigue.
Although, as with many diseases, myasthenia gravis can occur at almost any age, it seems to affect more women under 40 and more men over 60 years of age, and in the United States affects about 20 individuals for every 100,000 members of the population.
Some of the most famous people in the world have suffered from this terrible disease, such as Aristotle Onassis, the billionaire Greek shipping magnate who married Jackie Kennedy after JFK’s assassination.

Why Does Myasthenia Gravis Occur?

Scientists are still working out the details of why myasthenia gravis may occur. We know that everything from genetics to immune reactions to drugs may increase the likelihood of developing this condition. Some researchers also believe the thymus , an organ located underneath your breastbone that is responsible for the proper development of the immune system, may play a role in the aberrations that occur in this disease. It has been noted that certain individuals with myasthenia gravis have a thymoma, or a tumor of the thymus.

What we do understand a bit better is the end result of most cases of myasthenia gravis. In this condition, your own body produces little proteins called autoantibodies, which are antibodies that target an individual’s own body, organs, cells, and receptors for destruction or inactivation.
Normally, antibodies are supposed to target foreign invaders such as bacteria and viruses for destruction or inactivation. But in an autoimmune condition such as myasthenia gravis, the antibodies become directed against auto, or self.
Specifically, these autoantibodies attach themselves to the receptors on the skeletal muscles of your body; these are the muscles responsible for locomotion. By doing so, the antibodies prohibit the receptors on the muscles from receiving a specific signal or destroy the receptors outright. Namely, this signal comes from nerves innervating the skeletal muscles. These nerves release a neurotransmitter that activates muscles of locomotion, called acetylcholine.
Under normal conditions, the nerves release this acetylcholine and it lands on its receptor on the muscle the nerve innervates. Once it lands on the receptor on this muscle, the muscle gets all excited, contracts, and allows you to move. The release of acetylcholine occurs at the neuromuscular junction, the place where nerves meet the muscles they innervate. The space between the nerve ending and the muscle it controls is known as the synaptic cleft.
That’s what happens normally. However, in people with myasthenia gravis the autoantibodies bind to the receptors on the muscle cells and thereby destroy or inactivate them.
You can liken the autoantibodies to our monkey in the middle, the nerve and muscle to our two players, the space between the two players as the synaptic cleft, the acetylcholine to our ball, and the receptors on the muscle cells to the hands of our player called ‘the muscle.’
The nerve player wants to pass the ball to the muscle player, but the monkey latches onto the hands of the muscle player and blocks the muscle player from ever catching the ball. If the ball can’t pass from one end to the other and can’t land in the muscle’s hands because those hands are blocked by the monkey, then the muscle player cannot become all excited about catching the ball, becomes depressed instead, and refuses to move because the game is no fun anymore.

Clinical Signs, Symptoms, and Diagnostics

Since the muscles are no longer excited to move, you shouldn’t be shocked by the typical signs and symptoms associated with myasthenia gravis, which means ‘grave muscle weakness’ through its ancient Latin and Greek roots. These signs include:
  • Difficulty walking, eating, speaking, smiling, and swallowing
  • Droopy eyelids and double vision
  • In serious cases, respiratory failure, when the muscles of respiration can no longer work.

Thursday, October 22, 2015

What is it like to have Myasthenia Gravis?

What is Myasthenia Gravis?

Myasthenia gravis is a neuromuscular disorder characterized by variable weakness of voluntary muscles, which often improves with rest and worsens with activity. The condition is caused by an abnormal immune response.

What is it like to have Myasthenia Gravis?


Common symptoms
What people are taking for it
Pregabalin, Hydrocodone-Acetaminophen, Codeine-Acetaminophen

Zolpidem, Clonazepam, Gabapentin
Amphetamine-Dextroamphetamine, Wheelchair (powered), Amantadine
Alprazolam, Paroxetine, Lorazepam
Bupropion, Diet and exercise, Escitalopram


What do patients take to treat Myasthenia Gravis and its symptoms?


Treatments reported by members


(Kalymin 60N, Mestinon)


(Pulmison, Pronizon, Deltasone, Encorton)



(Carimune, Privigen, Pentaglobin, Sandoglobuline)



(Imurek, Azasan, Azapress, Imurel)






These charts show data from Myasthenia Gravis patients’ latest treatment evaluations
Last updated:

  • Major
  • Moderate
  • Slight
  • None
  • Can't tell
  • Severe
  • Moderate
  • Mild
  • None


Who has Myasthenia Gravis on PatientsLikeMe?


  • 266 patients have this condition
  • 3 new patients joined this month
  • 192 say Myasthenia Gravis is their primary condition

Age
Age Proportion # of patients
<20 3
20s 12
30s 36
40s 58
50s 75
60s 34
70+ 15

Gender

Distribution of females vs. males
74% Females
26% Males
Age at first symptom
Age at first symptom Proportion # of patients
0-19 years 17
20-29

Thursday, October 15, 2015

Genetic Research Reveals Possible New Targets For Treatment Of Myasthenia Gravis October 15, 2015 Smith

NEW YORK – A new genome-wide association study suggests that immunomodulating drugs already approved by the U.S. Food and Drug Administration (FDA) could benefit patients with myasthenia gravis.
Dr. Bryan Traynor, chief of the Neuromuscular Diseases Research Section at the National Institutes of Health in Bethesda, Maryland, and colleagues, found three different disease-associated loci in myasthenia gravis patients. One locus was at CTLA4, and the FDA has approved two CTLA4-targeting treatments, abatacept and belatacept, for treating rheumatoid arthritis and renal transplant patients, respectively.
The findings also showed two distinct, but overlapping, disease-associated loci for the early- and late-onset forms of the illness
 ACh illustration
“The discovery of a genetic locus is always an exciting thing, but often times it can take 10 to 15 years between the discovery of a particular locus and a first-in-humans clinical trial,” Dr. Traynor told Reuters Health in a telephone interview. The fact that drugs targeting CTLA4 are already FDA approved should accelerate that timeline, he added.
In their study, published online February 2 in JAMA Neurology, Dr. Traynor and his colleagues looked at DNA from more than 1,000 white, North American patients with acetylcholine-receptor antibody positive myasthenia gravis and nearly 2,000 controls.
They investigated associations between more than 8 million variants and myasthenia gravis risk. Significant association signals were found at CTLA4 (odds ratio, 1.37); HLA-DQA1 (OR, 2.31) and TNFRSF11A (OR, 1.31).
The CTLA4 and HLA-DQA1 associations were replicated in a cohort of 423 myasthenia gravis patients and 467 controls from Italy.
The analysis also confirmed past observations that myasthenia gravis strikes younger patients, who are usually female, as well as patients 60 and older who are usually male.
We were able to find different genetic loci that drive genetic susceptibility in each case,” Dr. Traynor said. “We genetically proved that they are two fundamentally different conditions, but overlapping conditions as well.”myasthenia-gravis-18-638
The CTLA4 associations were seen in both early- and late-onset patients, the researcher noted. It’s likely, he added, that clinical trials testing CTLA4-targeting drugs in myasthenia gravis would enroll all patients with the illness, regardless of their genotype.
Even in patients who don’t have the CTLA4 variants he and his colleagues identified, Dr. Traynor noted, “it’s possible that in the other patients there are other variants in that region that are altering CTLA4 function, but we are not powered to pick it up.”
While effective therapy for myasthenia gravis is available, the researcher added, some patients with the disease do wind up having significant problems. “I think there is considerable room to grow new treatments,” Dr. Traynor said.
Dr. Robert Lisak of Wayne State University School of Medicine in Detroit co-authored an editorial accompanying the study.
“As in other complex immune-mediated disorders, there is an important influence of minor changes in multiple genes, likely interacting with the environment and with one another and their protein products, in the pathogenesis of myasthenia gravis,” Dr. Lisak told Reuters Health by email. “And in an autoimmune disease it is not surprising that the minor changes occur in genes for proteins that are critical in the immune response.”
“Identifying changes in genes in patients with different types of myasthenia gravis has the potential to help us understand which molecules and pathways in the immune system are the most important in development of disease,” he added. “In theory that might help in development of more-focused treatments for patients with myasthenia gravis. Only time will tell if this ultimately happens.”