Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Heart Drug Effective for Treating Symptom of Muscular Dystrophy

05.05.2010
A medication most often used to treat heart arrhythmias also reduces a central symptom of myotonic dystrophy, the most common type of muscular dystrophy in adults.

The findings about the medication mexiletine – a chemical cousin of lidocaine – were published May 4 in the journal Neurology, a publication of the American Academy of Neurology.

Currently there is no drug approved to treat myotonic dystrophy, an inherited disease that is marked by progressive muscle weakness. While the course of the disease can vary dramatically from patient to patient, symptoms besides weakness can include muscle stiffness, difficulty speaking and swallowing, problems walking, and in some patients, heart problems and cataracts. Physicians estimate that approximately 40,000 Americans have the condition.

The researchers at the University of Rochester Medical Center found that mexiletine is effective at treating the myotonia – muscle stiffness – that is at the center of the disease. Turning a key in a lock, writing with a pen or pencil, picking up and setting down a pitcher of water – all are formidable tasks for patients with myotonia. Sometimes the symptom first occurs when a patient shakes someone’s hand, then cannot relax his or her grip for several seconds.

While several doctors have suspected that mexiletene helps relieve myotonia, this is the first placebo-controlled, double-blind study to show that it actually does so, said neurologist Richard Moxley III, M.D., an author of the study and an international expert on muscular dystrophy.

“It’s important for physicians who treat patients to know that mexiletine is an option,” said Moxley, who is director of the University’s Neuromuscular Disease Center and professor of Neurology. “Several physicians who specialize in treating patients with myotonic dystrophy have found it to be effective for their patients, but we really wanted to study the issue closely. The medication really addresses myotonia quite well, with no additional risk.”

The findings come from one of the world’s premier groups focusing on research and new treatments for muscular dystrophy. Ten years ago Moxley began the world’s first muscular dystrophy registry, which now includes more than 1,500 patients with either myotonic dystrophy or facioscapulohumeral dystrophy.

Moxley also heads the University’s Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, one of three research centers originally created in 2003 by the National Institutes of Health. The Rochester center is now one of six NIH Wellstone centers and most recently received $5 million in additional funding in September 2008 to continue its work for five more years.

In the trial of mexiletine, evaluators measured the amount of time it took patients to relax their grip after squeezing the handles of a computerized device that measures force. For most healthy people, that relaxation takes one-third of a second or less. But for people with myotonic dystrophy, that relaxation can take many seconds.

Scientists studied two groups of 20 patients who had myotonic dystrophy, all confirmed through genetic analysis. Each participant received either placebo, or 150 or 200 milligrams of mexiletine three times a day, for seven weeks. Then, after a period of several weeks where they received no drug, participants were switched to the other treatment for another seven weeks.

The team found that mexiletine at three daily doses of either 150 or 200 milligrams per dose does a great deal to alleviate myotonia. In their test of relaxation after grip, the team found that mexiletine reduces the abnormally long relaxation by 38 percent at the lower dose and 59 percent at the higher dose. No benefit at all was seen for participants on placebo.

Because the drug can affect the heart, participants in the study were admitted as inpatients and stayed several nights at the University’s Clinical Research Center, where their heart health could be monitored closely. The team found no adverse effects of mexiletine, including no effects on normal cardiac rhythms.

Mexiletine acts to help the muscle compensate for the ion channel abnormality that is at the core of the myotonia in this disease. The myotonia is caused by a sort of molecular stutter that causes electrical signaling in muscle cells to go awry, in effect making muscle stick in the “on” position. The mutation markedly reduces the number of functioning muscle chloride channels and causes decreased movement of the chloride ion across the muscle membrane, leading to excessive muscle irritability and repeated spontaneous activation of muscle fibers. This results in muscle stiffness and delayed relaxation after contraction. Mexiletine works through the sodium channel, which is functioning normally, to decrease muscle irritability.

The new research findings on the effectiveness of mexiletine come amid several exciting research finds by Moxley’s colleagues. In one line of research, led by Charles Thornton, M.D., researchers have discovered precisely how a faulty gene actually causes myotonic dystrophy by preventing normal proteins from doing their jobs. Thornton’s group then used experimental compounds to break up abnormal cellular deposits of toxic RNA in the nuclei of cells, eliminating myotonia in mice with myotonic dystrophy. Down the hall, a team led by Rabi Tawil, M.D., is part of an international study examining the genetic roots of the second most common form of muscular dystrophy in adults, facioscapulohumeral muscular dystrophy.

In addition to Moxley, authors of the paper include Neurology faculty members Eric Logigian, M.D., and Charles Thornton, M.D., and Biostatistics faculty member Michael McDermott, Ph.D. Also taking part from Rochester were William Martens, Richard Moxley IV, Nuran Dilek, A. T. Pearson, Cheryl Barbieri, and Christine Annis. Allen W. Wiegner, Ph.D., of Harvard also contributed.

The work was funded by the Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, the U.S. Food and Drug Administration, the National Institutes of Health, the Muscular Dystrophy Association of America, and the Saunders Family Neuromuscular Research Fund.

For Media Inquiries:
Tom Rickey
(585) 275-7954
Email Tom Rickey

Tom Rickey | EurekAlert!
Further information:
http://www.urmc.rochester.edu

More articles from Health and Medicine:

nachricht Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center

nachricht Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>