Enzyme Replacement Therapy Improves Outcomes In Fabry's Disease

Main Category: Biology / Biochemistry
Article Date: 02 Dec 2009 - 0:00 PDT

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A five-year study has shown that enzyme replacement therapy improves clinical outcome, including reducing pain and improving quality of life, in patients with Fabry's Disease. This is the conclusion of an Article in this week's edition of The Lancet, written by Dr Atul Mehta, Royal Free Hospital, London, UK, and colleagues.

Fabry's disease is a rare progressive multisystem disorder resulting from lack of an enzyme (?-galactosidase A), which is essential in various metabolic pathways. Kidney failure, cardiomyopathy (a disease of the heart muscle, making it abnormal with no obvious cause), and cerebrovascular disease (disease of the blood vessels supplying the brain) are the main causes of disease and premature death. In this study, the authors assessed the effect of an enzyme replacement therapy (agalsidase alfa) on heart mass and function, renal function, pain, and quality of life. Data from the Fabry Outcome Survey observational database was used for the study. The Fabry outcome survey is international, comprising data from Europe, North America, and South America.

The research team found that In patients with baseline cardiac hypertrophy (oversized heart), treatment resulted in a sustained reduction in left ventricular mass (LVM) index after 5 years of around 10%; and a significant increase in midwall fractional shortening (MFS) (Q: please explain in lay terms what MFS is) from 14•3% to 16•0% after 3 years. In patients without baseline hypertrophy, LVM index and MFS remained stable. Kidney function was assessed using mean yearly fall in estimated glomerular filtration rate versus baseline after 5 years of enzyme replacement therapy, and this was found to be -3•17 mL/min per 1•73 m² for men and -0•89 mL/min per 1•73 m² for women (Q: why more for men than women). Average pain, measured by Brief Pain Inventory score, improved significantly, from 3•7 (2•3) at baseline to 2•5 (2•4) after 5 years. Quality of life scores also improved in patients given replacement therapy.

The authors say: "Our results show sustained benefits of agalsidase alfa during 5 years of treatment."

Dr Mehta adds: "These long term 'real life' registry data confirm the hopes raised by short term clinical trials, commenced over 10 years ago. ERT has the potential to prolong quality life in this often fatal illness. "

In an accompanying Comment, Dr Ravi Thadhani, Renal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA, and colleagues say: Enzyme-replacement therapy has only been available typically since 2001 and, thus, duration of exposure might be too short to assess whether this strategy prolongs life. Keeping the high cost of this lifelong treatment front and centre, we await confirmatory evidence of a reduction of clinical events with an extension of life."

They conclude: "We are registered for success, and confirmation of this achievement will hopefully follow."

Source
The Lancet

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