GI Symptoms in LOPD Widespread, Study Finds
More attention should be given to evaluating the gastrointestinal symptoms of individuals with late-onset Pompe disease (LOPD) because they cause a significant disease burden, according to a recent study.
The results of that study highlight the need for more effective smooth muscle-targeted therapies in LOPD, as current treatments often provide insufficient relief.
The study, “New Insights into Gastrointestinal Involvement in Late-Onset Pompe Disease: Lessons Learned from Bench and Bedside,” was published in the Journal of Clinical Medicine.
Understanding of LOPD has evolved, from thinking of it mainly as a disorder affecting the lungs and the muscles of the limbs, to acknowledging the involvement of the smooth muscles of the gastrointestinal (GI) system, which includes the mouth, pharynx, esophagus, stomach, and intestines.
Relatively little remains known, however, regarding exactly how LOPD affects the GI system. This lack of understanding likely results in LOPD-related GI issues frequently going underreported or misdiagnosed.
To better understand the burden that GI problems place on individuals with LOPD, and the extent to which enzyme replacement therapy (ERT) helps with these issues, researchers affiliated with Duke University Medical Center in North Carolina surveyed LOPD patients regarding their GI symptoms. They also examined biological changes taking place in the GI systems of a mouse model of Pompe disease.
To get a sense of LOPD’s GI-related disease burden, the investigators administered the Patient-Reported Outcomes Measurements Information System (PROMIS)-GI symptom questionnaire to 58 adults living with the disorder. This group consisted of 35 women and 23 men, of median age 51.5 years. Of those, 53 were taking ERT, one had begun ERT but later discontinued it, and four had never taken ERT.
Thirty-eight participants had a GI-focused medical history, 32 of whom also completed the PROMIS-GI survey.
Overall, responses to PROMIS-GI indicated that GI problems were both prevalent and severe among those with LOPD.
Most participants with GI-focused medical history reported at least one GI issue (76%), the majority of whom did not change in response to ERT (82%).
Approximately 40% of these same participants reported their GI manifestations comprised one of the top three symptoms affecting their quality of life.
GI symptoms often preceded LOPD diagnosis (16 of 38 cases, or 42%). Age at onset of GI symptoms ranged from childhood to the 70s among the participants.
The researchers suggested that GI complications early in life could mean they form an early manifestation of LOPD, making their presence a consideration of Pompe and an indicator of disease progression.
“More than ever, monitoring disease manifestations and progression is important in LOPD with its inclusion in newborn screening programs, and with improved diagnostic criteria,” they wrote.
“The use of the PROMIS-GI measures in routine follow-ups could provide useful information about clinical progression of the disease and the effectiveness of emerging therapies,” they suggested.
Turning to mice, the scientists observed widespread physical evidence of GI involvement in Pompe-like disease, with glycogen — the complex sugar that the body fails to break down in the disorder — accumulating along the length of the GI tract.
“The current study showed that the GI tract is involved in its entirety, from the tongue and esophagus to the rectum,” they wrote.
The group tested the effect of short-term (five weeks) and long-term (six months) ERT on the signs of Pompe-like disease in the mice’s GI tracts, and found that long-term treatment more effectively cleared out glycogen than short-term ERT.
Starting therapy earlier in the course of the disease might be more effective than beginning later, they suggested. Yet, more research, following up older mice is needed to better understand the effectiveness of ERT on the gut when started later in life, the scientists said.
“GI manifestations cause a significant disease burden on adults with LOPD,” the researchers concluded, “and should be evaluated during routine clinical visits, using quantitative tools (PROMIS-GI measures). The study also highlights the need for next generation therapies for Pompe disease that target the smooth muscles.”
They said their study raises a question about the effectiveness of ERT in people with LOPD, but having only six patients in the untreated group precluded statistical comparisons with those on that form of therapy.