PMID- 24692796
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140402
LR  - 20211021
IS  - 0011-393X (Print)
IS  - 0011-393X (Linking)
VI  - 69
IP  - 2
DP  - 2008 Apr
TI  - Genistin-rich soy isoflavone extract in substrate reduction therapy for 
      Sanfilippo syndrome: An open-label, pilot study in 10 pediatric patients.
PG  - 166-79
LID - 10.1016/j.curtheres.2008.04.002 [doi]
AB  - BACKGROUND: Mucopolysaccharidoses (MPSs) are a group of severe metabolic 
      disorders caused by deficiencies in enzymes involved in the degradation of 
      glycosaminoglycans (GAGs)-long chains of sugar carbohydrates in cells that help 
      build bone, cartilage, tendons, corneas, skin, and connective tissue. Although 
      enzyme replacement therapy has become available for the treatment of some types 
      of MPS, effective treatment of neurodegenerative forms of MPS has yet to be 
      determined. Recently, genistein (4',5,7-trihydroxyisoflavone), a specific 
      inhibitor of protein tyrosine kinase, has been found to inhibit GAG synthesis and 
      to reduce GAG concentrations in cultures of fibroblasts of MPS patients. 
      Therefore, a potential substrate reduction therapy has been proposed. OBJECTIVE: 
      The aim of this study was to examine urinary GAG concentration, hair morphology, 
      and cognitive function in patients receiving genistin treatment for Sanfilippo 
      syndrome (MPS type III). METHODS: Patients aged 3 to 14 years with a 
      biochemically confirmed diagnosis of MPS IIIA or MPS IIIB were eligible to enroll 
      in this open-label, pilot study. Genistin-rich soy isoflavone extract 5 mg/kg/d 
      was administered PO for 12 months. Urinary GAG concentration, hair morphology,and 
      cognitive function (measured using a modified version of the Brief Assessment 
      Examination [BAE] and parent observations)were measured at baseline and after 12 
      months of treatment. RESULTS: Ten patients (6 girls, 4 boys; mean age, 8 years 
      [range,3\2-14 years];mean weight, 28 kg [range, 17\2-43 kg]) were included in the 
      study. All patients had Sanfilippo syndrome; 5 patients had MPS IIIA and 5 had 
      MPS IIIB. After 1 year, statistically significant improvement was found in 
      urinary GAG concentration, hair morphology, and cognitive function. Urinary GAG 
      concentration decreased significantly in all 5 patients with MPS IIIA and in 2 
      patients with MPS IIIB (P = 0.028). Hair morphology improved significantly in all 
      5 MPS IIIA patients and in 3 MPS IIIB patients (P = 0.012). A significant 
      increase in the BAE score (by 2-6 points) was noted in 8 patients, while the 
      scores of 2 patients did not change after 12 months of treatment (P = 0.012). No 
      adverse events (AEs) considered related to treatment were reported. Moreover, no 
      AEs not related to the treatment (apart from classical symptoms of MPS III) were 
      noted. CONCLUSIONS: 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.
FAU - Piotrowska, Ewa
AU  - Piotrowska E
AD  - Department of Molecular Biology, University of Gdansk, Gdansk, Poland.
FAU - Jakobkiewicz-Banecka, Joanna
AU  - Jakobkiewicz-Banecka J
AD  - Department of Molecular Biology, University of Gdansk, Gdansk, Poland ; 
      Laboratory of Molecular Biology, Institute of Biochemistry and Biophysics, Polish 
      Academy of Sciences, Gdansk, Poland.
FAU - Tylki-Szymanska, Anna
AU  - Tylki-Szymanska A
AD  - The Children's Memorial Health Institute, Warsaw, Poland.
FAU - Liberek, Anna
AU  - Liberek A
AD  - Department of Pediatrics, Children's Gastroenterology and Oncology, Medical 
      University of Gdansk, Gdansk, Poland.
FAU - Maryniak, Agnieszka
AU  - Maryniak A
AD  - The Children's Memorial Health Institute, Warsaw, Poland.
FAU - Malinowska, Marcelina
AU  - Malinowska M
AD  - Department of Molecular Biology, University of Gdansk, Gdansk, Poland.
FAU - Czartoryska, Barbara
AU  - Czartoryska B
AD  - Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland.
FAU - Puk, Ewa
AU  - Puk E
AD  - Biofarm, Poznan, Poland.
FAU - Kloska, Anna
AU  - Kloska A
AD  - Department of Molecular Biology, University of Gdansk, Gdansk, Poland.
FAU - Liberek, Tomasz
AU  - Liberek T
AD  - Department of Nephrology, Transplantation, and Internal Medicine, Medical 
      University of Gdansk, Gdansk, Poland.
FAU - Baranska, Sylwia
AU  - Baranska S
AD  - Department of Molecular Biology, University of Gdansk, Gdansk, Poland.
FAU - Wegrzyn, Alicja
AU  - Wegrzyn A
AD  - Laboratory of Molecular Biology, Institute of Biochemistry and Biophysics, Polish 
      Academy of Sciences, Gdansk, Poland.
FAU - Wegrzyn, Grzegorz
AU  - Wegrzyn G
AD  - Department of Molecular Biology, University of Gdansk, Gdansk, Poland.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Curr Ther Res Clin Exp
JT  - Current therapeutic research, clinical and experimental
JID - 0372621
PMC - PMC3969963
OTO - NOTNLM
OT  - gene expression
OT  - genistein
OT  - genistin
OT  - mucopolysaccharidosis
OT  - substrate reduction therapy
EDAT- 2008/04/01 00:00
MHDA- 2008/04/01 00:01
PMCR- 2008/04/01
CRDT- 2014/04/03 06:00
PHST- 2008/01/04 00:00 [accepted]
PHST- 2014/04/03 06:00 [entrez]
PHST- 2008/04/01 00:00 [pubmed]
PHST- 2008/04/01 00:01 [medline]
PHST- 2008/04/01 00:00 [pmc-release]
AID - S0011-393X(08)00036-2 [pii]
AID - 10.1016/j.curtheres.2008.04.002 [doi]
PST - ppublish
SO  - Curr Ther Res Clin Exp. 2008 Apr;69(2):166-79. doi: 
      10.1016/j.curtheres.2008.04.002.