Early treatment with enzyme replacement therapies targeting the underlying cause of Fabry disease may help delay cardiac manifestations and heart disease progression in Fabry patients, according to Japanese researchers.
Their study, “The beneficial effects of long-term enzyme replacement therapy on cardiac involvement in Japanese Fabry patients,” was published in the journal Molecular Genetics and Metabolism.
Farby disease is an inherited disorder caused by the accumulation of fatty molecules called globotriaosylceramides (Gb3) in various organs. As the disease progresses, patients can experience serious kidney problems, as well as heart and brain complications.
Treatment with enzyme replacement therapies (ERTs) such as Replagal (agalsidase alpha) and Fabrazyme (agalsidase beta) have been shown to effectively reduce Gb3 levels and prevent disease progression.
But these therapies have only recently been approved, and there is little information on possible long-term effects.
Researchers reviewed the clinical records of 42 patients with Fabry disease who were followed at Jikei University Hospital in Tokyo. The team focused on the long-term impact of ERTs for heart involvement because cardiac disease is the leading cause of death in Fabry patients.
Patients were followed for a mean period of 9.1 years after enzyme replace therapy was started. During this period, several changes in cardiac parameters were found, more significantly in male than in female patients.
The values of left ventricular mass index (LVMI), a measure of risk for heart impairment and disease, tended to gradually increase during long-term treatment. However, this change was not statistically significant in either men or women.
Female patients who had left ventricular hypertrophy — a thicker wall of the heart’s main pumping chamber — experienced faster LVMI progression than patients who did not have this heart abnormality.
In male patients, left ventricular hypertrophy did not change the progression rate of LVMI during ERT treatment.
Collectively, the researchers failed to find “any initial [cardiac function] improvement within a few years after the initiation of ERT.” Instead, “a gradual increase in the LVMI was observed over long-term ERT,” they wrote.
Importantly, patients who had worse kidney function were also those with worse LVMI progression during ERT treatment.
European and United States guidelines recommend that ERT treatment in males should be started as soon as possible. But in female patients, ERTs are commonly indicated only if serious complications occur.
Based on the study’s findings and the prevalence of cardiac manifestations in Japanese female patients, the researchers suggest that ERT should be initiated “when female Fabry patients are in their 30s or younger, in order to prevent the onset of serious complications.”
However, “the optimal timing for the start of ERT remains controversial, both from the viewpoint of cost-effectiveness and due to social issues, and it should be systematically verified in the future,” they wrote.
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