Researchers have found that the drug albuterol appears to be beneficial in two forms of congenital myasthenic syndrome (CMS)— CMS related to mutations in the collagen Q (colQ) gene and CMS related to mutations in the DOK7 gene.
MDA funded Andrew Engel, professor of neurology at the Mayo Clinic in Rochester, Minn., for this work. The findings were published in the November 2011 issue of Muscle & Nerve. (See Beneficial effects of albuterol in congenital endplate acetylcholinesterase deficiency and Dok-7 myasthenia.)
The results are from an open-label trial in which all participants knew they were taking albuterol, a drug approved for the treatment of asthma and other respiratory disorders. Although placebo-controlled trial results are considered more conclusive, until such a trial can be conducted, Engel says he would "not withhold albuterol from seriously ill patients" with DOK7-related or colQ-related myasthenic syndromes.
Eighteen trial participants ages 5 to 58 received albuterol by mouth for periods ranging from one month to two years. Median treatment time was four months.
Response to albuterol was evaluated by questionnaires about functional abilities given to participants or their parents.
All except one of the participants reported an increase in quality of life with this medication, which has U.S. Food and Drug Administration approval as a treatment to dilate air passages in asthma and other lung disorders. It isn't clear why the drug helps in CMS.
Some trial participants were able to return to work or school, some no longer required a wheelchair, one no longer needed nighttime ventilation, and one became nearly symptom-free.
Only one person (a different participant from the one who didn't respond to albuterol) had an adverse effect that was significant enough to warrant stopping albuterol. This person experienced an abnormal heart rhythm, and the medication was stopped after two weeks.
Congenital myasthenic syndromes are genetic conditions that result in defective nerve-to-muscle signal transmission, with resulting weakness. Nerve-to-muscle signal transmission takes place at neuromuscular junctions, places where nerve fibers activate muscle fibers. They do this via a chemical neurotransmitter called acetylcholine, which lands on docking sites on muscle fibers called acetylcholine receptors.
There are many types of CMS, and most of them respond well to medications, such as pyridostigmine, that increase the amount of acetylcholine at the neuromuscular junction. DOK7-related CMS and colQ-related CMS, however, do not respond to this type of treatment, and some people with DOK7-related CMS are worsened by it.
Of the 18 people in this study, 15 had DOK7gene mutations, which result in structural abnormalities at the neuromuscular junction.
Three had COLQ gene mutations that adversely affect an enzyme called acetylcholinesterase. This enzyme normally breaks down acetylcholine at the neuromuscular junction, after the neurotransmitter has activated a muscle fiber. This inactivation is necessary for continued neuromuscular signal transmission.
Other types of myasthenia, including myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS), are not genetic, but are autoimmune. They result from an attack of the immune system on various parts of the neuromuscular junction and are treated with immunosuppressants and other medications.
For more about congenital myasthenic syndromes, read the June 2001 Quest story on CMS.
In the open-label albuterol trial, there was no placebo group and participants knew when they were on and off albuterol. The gold standard for evaluating safety and effectiveness of a drug is a double-blind placebo-controlled trial, in which neither participants nor investigators know who is receiving the experimental treatment or placebo (fake treatment).
However, that type of trial is difficult to conduct when a disease is rare and affected people live far apart from each other.