Delays in Enzyme Replacement Therapy Can Lead to Persistent Damage, Study Says

Delays in Enzyme Replacement Therapy Can Lead to Persistent Damage, Study Says

Delaying the start of enzyme replacement therapy (ERT) may lead to worse symptoms and, potentially, permanent damage in patients with Gaucher disease (GD).

The study, “Time of initiating enzyme replacement therapy affects immune abnormalities and disease severity in patients with Gaucher disease,” published in PLOS One, underscores the importance of early diagnosis and treatment in preventing persistent alterations to the immune system.

GD patients often show abnormalities in immune response that may be the result of alterations in cellular and/or humoral immunity. It is important to explore how these systems are affected by the disease, its clinical features and its treatment.

Enzyme replacement therapy (ERT) is the most accepted form of treatment for GD, and has well-established therapeutic goals (changes in liver and spleen size, improvement in blood parameters, bone pain and bone crises). It is given by intravenous infusion to supplement the enzyme glucocerebrosidase, which is deficient in people with GD, leading to toxic accumulation of a fatty substance (glucocerebroside) in various organ systems.

Less than half of GD patients on ERT achieve those treatment goals, however, and ERT influence on their immunological status remains unclear.

Researchers, to better understand why, investigated the immune profile of 26 GD patients who had participated in an ERT study. The onset of GD symptoms, duration of ERT therapy, and treatment outcomes were evaluated. Patients were diagnosed with mild, moderate, or severe GD using disease severity scoring system criteria (DS3).

Results showed that GD patients displayed multiple types of immune abnormalities, including alterations in levels of immune system cells, such as T-cells and B-cells. Interestingly, those immune alterations did not correlate with GD type or biomarker levels. Instead, more persistent alterations were related to the timing of therapy initiation.

Those patients with more severe symptoms started ERT at a later stage than those with mild to moderate symptoms, clearly showing that a delayed onset of therapy resulted in more severe and persistent symptoms.

“[W]hile ERT may reverse some of these immune abnormalities, the immune cell alterations become persistent if therapy is further delayed,” the researchers concluded. “These findings have important implications in understanding the immune disruptions before and after treatment of GD patients.”

In other words, an early diagnosis is critical for initiating treatment early, to minimize the risk of permanent damage. Testing for Gaucher disease involves a diagnostic blood test to measure beta-glucosidase leukocyte (BGL) activity, and screening for genetic mutations.

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