6MWD Test Reliable Measure of Motor Decline in LOPD, Study Finds
The six-minute walk distance (6MWD) test is a reliable measure of declines in motor abilities in people with late-onset Pompe disease (LOPD), a two-year study that evaluated a series of such tests reported.
Other common measures of motor function and muscle strength failed to reliably detect such changes in ambulatory patients, the researchers noted.
“Our study showed that the 6MWD is a useful outcome measure to detect motor decline in treated LOPD patients,” the team wrote.
The study, “Six-Minute Walk Distance Is a Useful Outcome Measure to Detect Motor Decline in Treated Late-Onset Pompe Disease Patients,” was published in the journal Cells.
LOPD is a rare genetic disorder characterized by mutations that affect the acid alpha-glucosidase (GAA) enzyme and lead to the buildup of glycogen, a complex sugar, in cells.
Glycogen accumulation damages organs and tissues, especially muscles, leading to progressive muscle weakness and breathing difficulties. Depending on the mutations and how severely they affect GAA, disease onset can be in infancy, childhood, or adulthood.
LOPD is considered a less severe form of Pompe, with weakness generally affecting muscles in the torso and legs. A number of tests of motor function and muscle strength can be used to monitor its symptoms and progression.
These tests include the 6MWD, which assesses how far a person can walk in six minutes; the 10-meter walk test (10MWT), a timed test of walking speed; the timed up-and-go (TUG) test, evaluating mobility by how well and quickly a person can rise from a chair, walk a set distance and return to a seated position; and the hand grip and other tests of muscle strength.
A research team in Belgium evaluated these tests over two years to determine those most useful in identifying motor decline in patients. Their study enrolled 12 LOPD patients, five men and seven women, with a mean age of 51.3, and 12 healthy adults, matched by sex and age.
All patients were able to walk and being treated with Myozyme (alglucosidase alfa) — marketed as Lumizyme in the U.S. by Sanofi Genzyme — for a mean of 8.8 years at the study’s start (a baseline measure). Myozyme/Lumizyme is a GAA enzyme replacement therapy or ERT, a standard treatment for Pompe. Four of these 12 LOPD patients were using non-invasive ventilation at night.
Their motor symptom onset was at a mean age of 32.8, and they had a mean disease duration of 18.4 years.
Lung function, as assessed by the forced vital capacity (FVC) test, remained largely unchanged throughout the study.
The mean distance patients walked in six minutes, evaluated every six months, was seen to significantly decrease over the study, falling from 451.9 meters (about 1,480 feet) at baseline to 368.1 meters (1,207 feet) after two years, indicating a decline in walking abilities.
No differences in the 6MWD were observed between patients using nighttime ventilation and those who were not.
In contrast, distances achieved in 6MWD rose over the study’s time for healthy participants. At baseline, these people walked a mean of 661.3 meters (2,170 feet), increasing to 694.6 meters (2,279 feet) after two years. This increase did not reach significance, but came close and was “probably due to a training effect,” the researchers reported.
No significant changes in other measures of patients’ motor abilities, including the 10MWT and TUG, were seen at each measure assessed over the study’s course.
Muscle strength was evaluated with an instrument called a Biodex dynamometer. Significant declines only in the strength of leg muscles working as knee extensors were observed, in both patients and healthy controls, “at 12 months at both sides … at 18 months only at the right side … and at 24 months at both sides” relative to scores recorded at the study’s start, the researchers wrote.
Muscle strength in most other muscles assessed — those of the hips, shoulders, and elbows — showed no significant changes after two years.
Other measures, including the manual Medical Research Council sum score (MRC-SS) that evaluates global muscle strength and the hand grip test, also did not significantly change over two years in either group.
The lack of difference between patients and healthy controls could be explained in part by normal aging, the team noted.
“We conclude that the 6MWD is a useful outcome measure to detect motor changes in treated ambulatory late-onset Pompe disease patients and should be included as an endpoint in clinical trials in LOPD,” the researchers wrote.
The degree of decline recorded since the study’s start in patients, 83.8 meters, amounts to “about 18% of the initial mean value of 451.9 m[eters],” which “represents a clinically meaningful change,” they added.
The team noted, however, that other muscle strength tests, like those of quantitative isometric strength using the Biodex dynamometer, may be of use for longer-term studies. But its assessments and those of “hand grip strength, 10MWT and TUG proved not to be suitable outcome measure in this group of patients for a study duration of 2 years.”
Test advantages are that it is easy and inexpensive to perform, but it is limited by its inability to assess motor changes in patients who are not able to walk.
“Further studies are needed to … analyze the proper outcome measure for non-ambulatory LOPD patients,” the researchers wrote.