LOPD Patients Can Walk Farther After Enzyme Replacement Therapy

Walking distance improved in late-onset Pompe disease patients on enzyme replacement therapy (ERT), while their lung function and muscle strength remained unchanged, a meta-analysis has found.

More studies are, however, needed to confirm these findings and “to obtain more robust results about the clear clinical benefit of ERT,” the researchers wrote.  

The study, “Clinical efficacy of the enzyme replacement therapy in patients with late-onset Pompe disease: a systematic review and a meta-analysis,” was published in the Journal of Neurology.

In patients with Pompe disease, a deficiency of the enzyme acid alpha-glucosidase (GAA) results in a toxic accumulation of glycogen (a complex sugar molecule), primarily in muscle tissues. The first-line treatment for Pompe disease is Lumizyme, an ERT that uses a man-made version of GAA that mimics the activity of naturally occurring GAA in the body.

Now, researchers in Switzerland conducted a meta-analysis of published studies evaluating the efficacy of ERT in patients with late-onset Pompe disease (LOPD). The analysis focused on improvements in muscle strength, motor performance, and lung function measured by forced vital capacity — the amount of air a patient can forcibly exhale after a deep breath.

A total of 16 studies were included in the meta-analysis, with data from 589 patients with LOPD. The study follow-up times ranged from six months to seven years after treatment initiation.

Fourteen studies assessed motor performance in a total of 419 LOPD patients, 407 of whom received ERT. Their data showed that 18.75 months after starting ERT, patients showed an average increase of 32.2 meters in walking distance in the six-minute walk test (6MWT), compared with the distance walked at baseline.

In the 16 studies that assessed lung function in 563 LOPD patients (555 ERT-treated), forced vital capacity remained stable, with no significant change reported 20.75 months after treatment initiation. 

Similarly, in the 10 studies that evaluated muscle strength in 413 LOPD patients (388 ERT-treated), a slight increase in mean muscle strength was reported 19.5 months after treatment initiation but the change was not statistically significant.

“In conclusion, the available data showed that ERT has a significant beneficial efficacy in the improvement of walking distance in LOPD patients and a non-significant improvement of muscle strength,” the researchers wrote. “No improvement in respiratory capacity was found.”

According to the team, the study was limited by its small sample size, potential selection bias in patient inclusion, the variability of follow-up duration, and the exclusion of treatment efficacy measures other than 6MWT, forced vital capacity, and muscle strength.

Thus, further studies are needed to better characterize the therapeutic response to ERT in patients with LOPD “and, hence, patients who might benefit from the therapy,” the researchers wrote. “In fact, knowing which patients have a better response would allow a more efficient patient prioritizing and an optimizing of resources.”