A Review of Fabry Disease

Brandon Chan; David N. Adam, MD, FRCPC, DABD


Skin Therapy Letter. 2018;23(2):4-6. 

In This Article

Enzyme Replacement Therapy

Standard treatment for FD is enzyme replacement therapy (ERT). Currently, there are two forms of recombinant alpha-galactosidase A: agalsidase alfa, which is produced by continuous human cell lines, and agalsidase beta, which has been produced by Chinese hamster ovary cells transduced with the AGAL gene. According to a 2016 Cochrane Review, ERT has been shown to significantly alleviate the cardiac, renal, and neuropathic effects of FD.[15] The US FDA has only approved agalsidase beta for FD,[15] whereas both agalsidase alfa and beta are approved for FD in Canada. The Canadian Fabry Disease Initiative is a nation-wide study that is currently comparing the efficacy of the two ERT treatments.[16] The recommended dose is 0.2 mg/kg of body weight administered every 2 weeks for agalsidase alfa and 1 mg/kg of body weight every 2 weeks for agalsidase beta.[15]

Six randomized controlled trials (RCT) examining the effect of agalsidase beta on skin GL3 deposition have been performed. A 20-week long RCT in 1999 involving 58 patients with skin-GL3 deposits as a secondary endpoint found significantly lower GL3 deposits in skin, kidney, and heart biopsies, with 20 of 29 patients who received treatment experiencing clearance of renal capillary endothelial GL3 deposits (a score of 0 on a scale of 0–3).[17] In the subsequent 6-month open-label study, all patients in the former placebo group and 98% of patients in the former treatment group had scores of 0.[18] In the same cohort of patients enrolled in an open-label trial, complete clearance of GL3 skin deposits was reported in 98% of patients at 30 months and 86% of patients at 54 months.[19] Another RCT involving the same cohort examined dermatologic biopsies and found similar results, with scores of 0 (GL3 clearance) in superficial dermal capillary endothelial cells in 100% of adult patients, in deep dermal vascular endothelial cells in 85%, in vascular smooth muscle cells in 33%, and in the perineurium in 4%.[20] A 48-week open-label study from 2002 to 2005 with patients aged 8 to 16 years found clearance of GL3 deposits in superficial dermal capillary endothelial cells at 24 and 48 weeks, and a reduction from moderate/severe GL3 accumulation to mild/cleared GL3 accumulation in deep dermal capillary endothelial cells at 24 and 48 weeks.[21] Another openlabel study from 2003 to 2006 examining skin and kidney GL3 deposits administered the standard dose of 1 mg/kg every 2 weeks of agalsidase beta to 21 adult patients for 6 months, and then a reduced dose of 0.3 mg/kg every 2 weeks for 18 months. Ninety-five percent of patients had a score of 0 (no GL3 skin deposits) at week 24, compared to 24% at baseline. During the low dose period, only 70–80% of patients had scores of 0, with seven patients experiencing increasing scores and two patients experiencing new spontaneous AGK.[22]

A retrospective analysis involving 134 adult patients investigated the effects of immunoglobulin G (IgG) antibodies against agalsidase beta during treatment. No correlation was found between IgG titers and the onset of clinical events, renal function, or plasma GL3. However, a correlation was found between IgG titers and GL3 deposits in dermal capillary endothelial cells, with a larger proportion of patients with GL3 deposits in the highest titer subgroup.[23] The clinical significance of the possible effect of these antibodies is still unknown.