DAS-MG (GTP-004) is an investigational medication originally developed by GT Biopharma to treat muscle weakness associated with myasthenia gravis. In September 2010, the treatment was acquired by Das Therapeutics, which is continuing its clinical development.
What is myasthenia gravis?
Myasthenia gravis is an autoimmune disease in which the immune system (that normally helps fight infections) mistakenly attack healthy cells and tissues in the body.
In the case of myasthenia gravis, these antibodies are directed against the acetylcholine receptor found on muscle cells. Nerve cell endings release a signaling molecule called acetylcholine, which normally binds to these receptors, thereby transmitting the nerve signal to the muscle and ensuring that it contracts.
When the acetylcholine receptors are damaged by the immune system, acetylcholine cannot bind to the receptors and is destroyed by an enzyme called acetylcholinesterase. This results in a lack of communication between nerve and muscle cells, leading to muscle weakness and fatigue.
How does DAS-MG work?
Pyridostigmine, sold under the brand name Mestinon for the treatment of myasthenia gravis, is an acetylcholinesterase inhibitor, meaning that it works by blocking the enzyme that degrades acetylcholine. The medication ensures there is more acetylcholine available in the space between nerve and muscle cells, and the acetylcholine can then bind to any remaining receptors on the muscle cells. In this way, Mestinon helps to improve muscle strength and reduce the weakness and fatigue seen in people with myasthenia gravis.
However, Mestinon can also cause severe gastrointestinal side effects, such as diarrhea, nausea, and vomiting. Therefore, DAS-MG combines Mestinon with ondansetron, which blocks the action of chemicals in the body that can trigger nausea and vomiting.
By blocking the adverse effects of Mestinon while maintaining its effectiveness, DAS-MG may help improve patients’ comfort and enhance their compliance to treatment.
DAS-MG in clinical trials
The efficacy of DAS-MG has been evaluated in a Phase 1 proof-of-concept clinical trial in five healthy volunteers. The trial’s primary objective was to test whether DAS-MG can lead to a reduction in gastrointestinal side effects.
During the trial, participants received single doses of Mestinon (ranging from 30 to 120 mg) until they reached the first intolerable dose (FID). They then stopped taking Mestinon for two to seven days. The same process was repeated, but with participants receiving DAS-MG.
According to the results announced in March 2018, three people reached FID, which occurred at 60 mg for two people and 90 mg for the third person. When patients received DAS-MG, the gastrointestinal side effects were substantially reduced or completely eliminated, and all participants tolerated doses as high as 120 mg — the maximum allowed by the protocol.
Researchers also measured the blood concentrations of DAS-MG and Mestinon and saw nearly identical levels of Mestinon in the blood of the participants. This led the researchers to conclude that the reduced side effects were due to DAS-MG, rather than a decreased absorption of Mestinon when given in combination with ondansetron.
Last updated: Sept. 30, 2019
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