Question about myasthenia gravis?

In the disease myasthenia gravis, the immune system attacks the receptors for the neurotransmitter acetylcholine. A drug is used to inhibit the enzyme acetylcholinesterase which normally removes the neurotransmitter. This improves the condition of the patient. How does this work?

Myasthenia gravis means 鈥渟erious muscle weakness,鈥?which indicates this condition鈥檚 essential symptoms: weakness of the voluntary muscles and muscular fatigue.

The neurotransmitter acetylcholine acts very quickly on its receptor and is then rapidly broken down by an enzyme, as mentioned above. That enzyme is acetylcholinesterase. Drugs that cut back on the acetylcholinesterase in a person鈥檚 body allow the existing acetylcholine to interact repeatedly with the receptors. In other words, the muscle receives multiple signals from a single neurotransmitter molecule. This partially improves muscle strength and function but is only a temporary measure.

the inhibitors raise the level of acetylcholine(ACh) available to bind with the still functional receptors.

Myasthenia gravis (literally "serious muscle-weakness"; from Greek 渭蠉蟼 "muscle", 峒€蟽胃苇谓蔚喂伪 "weakness", and Latin gravis "serious"; abbreviated MG) is a neuromuscular disease leading to fluctuating muscle weakness and fatiguability. At 20 cases per 100,000 (in the U.S.),[1] it is one of the lesser known autoimmune disorders. Weakness is typically caused by circulating antibodies that block acetylcholine receptors at the post-synaptic neuromuscular junction,[2] inhibiting the stimulative effect of the neurotransmitter acetylcholine. Myasthenia is treated with immunosuppressants, cholinesterase inhibitors and, in selected cases, thymectomy.

http://en.wikipedia.org/wiki/Myasthenia_...
Tests on New Drug for MG
Ester Neuroscience Gets FDA Orphan Drug Status for Myasthenia Gravis

Herzlia, Israel
Ester Neurosciences announced today that the U.S. Food and Drug Administration has granted the company Orphan Drug Designation status for Monarsen, (formerly known as EN101), for the treatment of myasthenia gravis (MG).

Orphan Drug Designation status gives Ester, upon marketing approval, the exclusive right to market a drug of this kind for MG in the US for seven years. In addition to marketing exclusivity, the advantages of the designation include eligibility for research grants to conduct clinical trials, certain tax benefits, and an exemption from certain user fees at the time of submission for marketing approval of a new drug application. A similar Orphan Drug application has been made to European regulatory authorities.

"Obtaining orphan drug designation marks an important step in our regulatory strategy for Monarsen," said Dr. Eli Hazum, CEO of Ester Neurosciences.
"Current MG treatments which include anti-cholinesterases, steroids and immunosuppressants, offer limited efficacy and often cause unpleasant and sometimes dangerous side effects. Monarsen offers the prospect of an efficacious and safe product that can address a very large market," added Dr. Hazum.

The results of a successful Phase Ib trial for Monarsen were presented at a special Late Breaking Science session of the National Academy of Neurology earlier this year.
The breakthrough study was the first demonstration of the safe and effective use of an orally-administered anti-sense therapy for a neurological disease.

This study, where sixteen patients received oral liquid Monarsen, demonstrated significant improvement in MG symptom severity, with no cholinergic effects, nor significant adverse events. Fourteen out of sixteen patients had better scores on the Quantitative Myasthenia Gravis (QMG) scale on the last day of dosing as compared to the initial baseline. Improvement of total QMG score for these days ranged from 27.8% to 53.4% (p<0.01). The Phase Ib trial results showed that Monarsen appears to have superior efficacy, longer duration of action and a more favorable side effects profile than currently used medications. Patient recruitment for extended clinical trials with Monarsen is underway.

Monarsen is based on pioneering research carried out by Prof. Hermona Soreq of the Hebrew University, who serves as Ester's Chief Scientific Advisor. Monarsen offers a novel mechanism of action for the control of an isoform of the acetylcholinesterase enzyme that is believed to play a key role in the onset and progression of MG.

Myasthenia gravis is a chronic and debilitating autoimmune disease in which the body's immune system attacks acetylcholine receptors at the neuromuscular junction, interfering with normal muscular function. MG is characterized by general muscle weakness and excessive fatigue. In severe cases the disease can involve the respiratory muscles, causing potentially life-threatening respiratory failure.

Ester Neurosciences Ltd. is a clinical stage biotech company committed to the discovery and development of novel therapeutic products for the treatment of neurological disorders.



New MG Clinic in Sydney
A speciality clinic for Myasthenia Gravis and Myasthenic Syndromes has recently been established at Concord Repatriation and General Hospital, Sydney. This is one of several specialty neuromuscular disorders clinics run by the Department of Neurology. The Clinic can be contact on ph 02 97676416 and fax 02 97677807.

Particular aspects that this clinic is focused on are:

Ensuring that the diagnosis is secure, given that the treatments used in MG can have significant side effects.

The diagnosis of variants of MG, including anti-Musk MG, seronegative MG and Congenital Myasthenic Syndromes.

Treating the disorder while minimising side effects, especially as MG treatment is for the long term.

There are several treatment questions that need to be answered in international treatment trials and interested patients who are willing could participate through the clinic.


http://www.myasthenia.org.au/html/news.a...

You are probably refering to the drug neostigmine (Tensilon). Acetylcholinesterase typically breaks down the nuerotrasmitter acetylcholine. Acetylcholine is the neurotransmitter responsible for muscle contraction. A definiciency in acetylcholine causes muscle weakness or, in severe cases, paralysis (although usuall temporary). Neostigmine (Tensilon) stops acethylcholinesterase from breaking down acetylcholine thereby indirectly allowing a greater amount of acetylcholine to accumulate.

Acetylcholinesterase------------->Brea... down acetylcholine
Acetylcholinesterase------/TENSILON/--... Breaks down acetylcholine