Pharmacological chaperone treatment with Cystadane in aspartylglucosaminuria: an open-label, phase Ib/II trial

Abstract This phase Ib/II investigator-initiated, open label trial aims to show the safety and efficacy of Cystadane (betaine) in aspartylglucosaminuria, a lysosomal storage disorder characterized by progressive cognitive decline, in Finnish patients homozygous for the Finnish major mutation, aged between 3 and 17 years at study begin (recruited: 25, analyzed: 21). Oral Cystadane efficacy and safety were studied over 48 months. The primary endpoint of the study, reduction of glycoasparagines in the urine, was quantitatively determined using liquid chromatography/mass spectrometry and normalized to urine creatinine. Urine glycoasparagines are significantly reduced upon Cystadane treatment (by 68.6% ±10.8%; p = 0.000), and the study thus meets its primary endpoint. Our data show that Cystadane/betaine efficiently improves the main disease biomarker, and it is safe to use in aspartylglucosaminuria. Further studies should be carried out in a larger patient population over a longer time to demonstrate the effects on disease progression. EudraCT registration number 2017-000645-48.