Mucopolysaccharidoses (MPS) are severe, inherited metabolic disorders caused by storage of
glycosaminoglycans (GAGs). Sanfilippo disease (
mucopolysaccharidosis type III, MPS III) is described as severe neurological type of MPS, characterized by rapid deterioration of brain functions. No
therapy for Sanfilippo disease is approved to date, however, a specific substrate reduction
therapy (SRT), called gene expression-targeted
isoflavone therapy (GET IT), has been used as an
experimental therapy. In this report, we describe effects of treatment of six Sanfilippo disease patients with GET IT, in which the dose of
genistein (5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one), an active compound of GET IT present in the soy
isoflavone extract, has been increased to 10, and then to 15 mg/kg/day, contrary to the previously reported dose of 5 mg/kg/day. By measuring levels of urinary GAGs and assessing hair dysmorphology as
biomarkers, and by considering clinical symptoms of patients, we obtained results suggesting that elevated doses of
genistein may improve efficacy of GET IT for Sanfilippo disease.