ERT Prevents Lung Health Decline With Classic Fabry, Study Suggests
People with classic Fabry disease due to a common disease-causing mutation who don’t smoke can still have poorer lung health and symptoms like dry cough and shortness of breath, but these symptoms can stabilize with enzyme replacement therapy (ERT), a small study in Finland suggests.
These findings, in a group of adult classic Fabry patients followed for about five years, suggest that ERT works to preserve pulmonary function in addition to its well-established benefits for kidney and heart health.
The study “Pulmonary manifestations and the effectiveness of enzyme replacement therapy in Fabry Disease with the p. Arg227Ter (p.R227*) mutation” was published in the journal Molecular Genetics & Genomic Medicine.
Fabry disease is caused by no or little alpha-galactosidase A (Gal A) enzyme activity due to mutations in the GLA gene, with the subsequent lack of Gal A causing a toxic accumulation of fatty molecules in tissues and organs.
While the hallmark symptoms of classic Fabry — a more severe disease form — typically affect the skin, kidney, heart, and nervous system, the lungs can also be involved.
Previous studies, its researchers wrote, “demonstrated that pulmonary symptoms in [Fabry disease] can be independent of cardiac disease and the airway obstruction is disproportionate to smoking status.”
Lung symptoms of classic Fabry “include mild expiratory wheezing, dyspnea [shortness of breath], and dry cough,” with validated tests showing “mild, irreversible [airway] obstruction,” they added.
ERT, a mainstay Fabry treatment, involves the delivery of a lab-made version of the Gal A enzyme directly to a patient’s bloodstream, restoring its function. Two versions of this treatment are available commercially — Fabrazyme (agalsidase beta) and Replagal (agalsidase alfa). Fabrazyme is approved in the U.S., the European Union, and many other countries; Replagal is not approved in the U.S.
Both treatments’ ability to preserve kidney, heart, and neurological function have been widely studied, but less is known about ERT’s potential benefits for lung health.
Researchers in Finland evaluated lung function in 12 people (four males and eight females; all members of two different families) with classic Fabry associated with the common c.679C>T mutation. They also looked at the effects of ERT on pulmonary health, examined using validated measures before and after ERT initiation, with patients tested annually for a mean of 5.1 years.
This analysis was part of a larger study — called the Fabry follow‐up single mutation study in Finland (FAST) — to better understand the link between the c.679C>T mutation and disease symptoms, and to assess ERT in both men and women.
One of this study’s 12 patients had also been diagnosed with asthma, and one was a current smoker.
ERT was initiated at a mean age of 30 among the males (age range, 15–39) and at mean age of 52 among females (range, 25–66). Nine patients started on Fabrazyme and three on Replagal. Over the study follow-up years, two Replagal-treated patients were switched to Fabrazyme and one moved from Fabrazyme to Replagal.
Pulmonary function values from tests like forced vital capacity — the amount of air forcibly exhaled after a deep breath — before starting on ERT were available for nine patients. They showed airway obstruction in three people (33.3%; two women and one male), and borderline obstruction one male (11.1%).
Cardiopulmonary exercise tests given six of patients, including five women, showed normal maximal oxygen consumption during exercise in all but one person.
Airway obstruction was detected in two additional patients over the study’s five years, and by its end, four of these five patients were reported to have mild lung obstruction.
Measures of lung function remained generally unchanged over the study’s course in these patients, but treatment did not “reverse” the evident airway obstruction.
Thorax region computerized tomography available for six patients showed no changes in lung tissue. Overall disease severity, as assessed with the Mainz Severity Score Index, a validated test of disease progression, also remained unchanged over the study’s roughly five years.
About one-third of patients in a “predominantly nonsmoking” group with classic Fabry and the c.679C>T mutation in this study showed poorer lung function prior to starting on ERT, and all “remained stable during ERT,” the researchers wrote.
This finding, they added,”suggests that ERT stabilizes pulmonary function.”
Larger studies that include patients from other countries and those carrying other disease-causing mutations, the researchers wrote, are needed to more fully determine “pulmonary function course and the role of ERT” in people with classic Fabry.