This pilot study found some improvements in GAG concentration, hair morphology, and cognitive function in these pediatric patients with Sanfilippo syndrome treated with genistin-rich soy isoflavone extract for 1 year. Clinical trials are needed to evaluate the efficacy and safety of this potential treatment.

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SummaryBackgroundMucopolysaccharidoses (MPS) are inherited metabolic disorders caused by deficiencies in enzymes involved in degradation of glycosaminoglycans. MPS type III (Sanfilippo disease) is clinically characterized mainly by progressive and severe behavioral disturbances and cognitive dysfunction. Recent 1-year experimental treatment of 10 patients with a genistein (4′, 5, 7-trihydroxyisoflavone)-rich extract resulted in improvement of tested parameters, including cognitive and behavioral functions.Material/MethodsEight pediatric patients with Sanfilippo disease were enrolled into the study. The modified version of the Brief Assessment Examination was used to assess cognitive functions. Moreover, 18 different parameters concerning changes in conditions of patients were assessed by their parents.ResultsDuring the first year of the treatment, an improvement of cognitive functions in 7 patients and stabilization in 1 patient were assessed, while after the third year (2-year follow-up) further improvement was observed in 2 patients, stabilization in 3 patients and some deterioration in 3 patients. Monitoring of general and behavioral symptoms revealed improvement in all patients after the first year of the treatment, further improvement in 5 patients, and deterioration in 3 patients during the next 2 years.ConclusionsWe conclude that the treatment of Sanfilippo patients with a genistein-rich soy isoflavone extract (called gene expression-targeted isoflavone therapy [GET IT]) may be effective in either inhibition (in some patients) or slowing down (in other patients) of behavioral and cognitive problems over a longer period. An increased dose of genistein may improve the efficacy of the treatment.

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Mucopolysaccharidoses (MPS) are heritable, metabolic diseases caused by accumulation of mucopolysaccharides (glycosaminoglycans, GAGs) in lysosomes. This accumulation is due to a deficiency in one of several specific enzymes involved in the degradation of GAGs. MPS type I (MPS I) is caused by low or undetectable activity of alpha-L-iduronidase, an enzyme involved in removing the terminal iduronic acid residues from heparan and dermatan sulfate. Recently, an enzyme replacement therapy (ERT) for MPS I, based on administration of recombinant human alpha-L-iduronidase (laronidase, Aldurazyme), became available. The assessment of efficacy of ERT is especially important because MPS I is a highly variable and very rare disease, and the clinical trials involved relatively low number of patients. Among various significant clinical improvements during ERT, remarkable changes in hair morphology were noted. Detailed studies of hair samples from one patient, who did not have a hair cut from the beginning of ERT to the end of this study, and supported by results obtained for two other patients, revealed hair shaft structural abnormalities in MPS I hair. These hair abnormalities disappeared upon treatment with Aldurazyme. Although hair morphology is of limited clinical importance, the data suggest that changes in this parameter could be a useful, additional tool for a rapid, non-invasive, preliminary assessment of ERT efficacy.