Type 1 myotonic dystrophy (MMD1, or DM1) and type 2 myotonic dystrophy (MMD2, or DM2) are complex, multisystem disorders caused by similar genetic flaws on chromosome 19 (MMD1) and chromosome 3 (MMD2). Treatments that target the underlying molecular causes of MMD1 and MMD2 are in development. In the meantime, there are therapies that target the symptoms — such as excessive sleepiness — of these disorders.
Biotech companies team up to develop antisense for MMD1
The companies announced the collaboration June 29, 2012.
Antisense oligonucleotides are a leading experimental therapeutic strategy for MMD1, in which the goal is either to destroy toxic genetic material or block its harmful interactions with cellular proteins. Since MMD2 is caused by a genetic defect similar to that seen in type 1, the strategy has been proposed as a potential MMD2 treatment as well.
See MMD Research: Seeking to Free Proteins from a 'Toxic Web' to learn more about treatment-related research in MMD.
UK survey finds most MMD1 patients, caregivers like modafinil
Recently, a concerned group of U.K. physicians, in conjunction with an MMD patient support group, sent questionnaires about modafinil (Provigil, Nuvigil) to 1,736 recipients of the group's newsletter — people with MMD1 and other interested parties, such as family members. Responses to the survey were received from 145 people with MMD1 and 146 of their relatives, friends or caregivers.
The impetus for conducting the survey was a recent recommendation by the European Medicines Agency (EMA) that the use of modafinil be restricted to people with the brain disorder narcolepsy, which causes people to fall asleep suddenly and unexpectedly. The drug is taken by people with MMD1 to treat excessive daytime sleepiness. (Read Excessive Daytime Sleepiness Can Be 'Debilitating' in MMD1 and MMD2 to learn more about the effects of MMD on the brain's sleep-wake cycles and on respiratory muscles.)
The EMA report said the potential for serious side effects, including severe skin reactions and abnormal heart rhythms, outweighed the potential benefits of modafinil for conditions other than narcolepsy.
In the United States, modafinil is approved for use in narcolepsy, shift work disorder and obstructive sleep apnea. However, in both countries, the drug has been prescribed "off label" (for treating a condition other than those approved by a regulatory agency) for people with MMD1, and many physicians and patients have found it to be beneficial in this complex disorder.
The U.K. physicians found that, out of the 145 people with MMD1 who answered the survey, 118 were taking the drug. Of those, 114 found it had either "marked benefit" or "dramatic benefit" with respect to daytime sleepiness and fatigue; and 110 said they would be "very disappointed" or "devastated" if it were no longer available.
Only one person with MMD1 taking modafinil reported "chest pain," without further detail, and there were no other reports of cardiac symptoms. Two people reported skin problems, without indicating that these were serious.
Of the 145 people with MMD1 returning the survey, 27 said they were no longer taking modafinil — 20 because of side effects and seven because they did not perceive a benefit from the drug. The two most commonly reported side effects were insomnia (eight people) and headaches (four people). Two people reported heart palpitations.
Of the 146 relatives, friends or caregivers who responded, 124 said modafinil had "marked benefit" or "dramatic benefit" with respect to sleepiness or fatigue for the patient. Only 26 people said they noticed side effects they attributed to modafinil, with eight reporting headaches and nine reporting insomnia. Two people reported skin problems, and two reported palpitations in the person with MMD1.
Those answering the survey who said they would be "very disappointed" or "devastated" if modafinil were no longer available numbered 120 out of 146.
Many people said that, without modafinil, life would be much more difficult. Several people offered comments such as "I feel without this drug my husband would not have his job, or much of a life."
In their paper Modafinil for Excessive Daytime Sleepiness in Myotonic Dystrophy Type 1 — The Patients' Perspective, published in the July issue of Neuromuscular Disorders, the authors conclude, "On the basis of our extensive clinical experience, supported by the findings of the present study, we believe that modafinil may have a marked beneficial effect for a significant minority of patients with DM1 [MMD1] for whom EDS [excessive daytime sleepiness] is a major intrusion into their daily activities."
The authors also list eight recommendations for the continued use of modafinil in MMD1, including careful monitoring of heart function and recording of any adverse events, even those not clearly related to the drug. (Readers must have a subscription or pay a one-time fee to access the complete paper.)