MODERN APPROACHES TO THERAPY FOR CHILDREN WITH MUCOPOLYSACCHARIDOSIS

Mucopolysaccharidosis is the group of hereditary metabolic disorders; it is characterized by accumulation of glycosaminoglycans owing to storage of specific lysosomal enzymes. Background: Research objective was to study the influence of enzyme replacement therapy on a somatic state and psychomotor development of children with mucopolysaccharidosis type I and II of various severity in dynamics and to estimate its efficiency. Patients and methods: The data of five years' supervision over 13 patients with mucopolysaccharidosis type I and II is used in the research. During the work the therapy efficiency analysis is made by the following criteria: data of objective examinations, ultrasound investigation of liver, spleen and heart, quantitative determination of excretion of urine glycosaminoglycans, assessment of articular and abarticular affection by JADI scale, assessment of social age and social coefficient by Doll's scale. Results: The reliable distinctions in the contents of urine glycosaminoglycans and also by results of an objective assessment of the liver and spleen sizes and of ultrasonic research of the spleen area in 6 and 12 months of treatment in comparison with basic data are received. The reliable decrease in social coefficient indicator at the first stage of therapy is registered, and then distinctions have insignificant character. There was no essential dynamics of the articular status on treatment that is connected with process stabilization. There are no reliable evidences of both positive and negative dynamics on myocardium involvement, ultrasonic characteristics of the sizes of hepatic lobes. Conclusion: Enzyme replacement therapy is an effective method of treatment of somatic manifestations of various types of mucopolysaccharidosis.

1. Combination of enzyme replacement and hematopoietic stem cell transplantation as therapy for Hurler syndrome. Bone Marrow Transplant. 2008; 41: 531–535.

2. D’Aco K., Underhill L., Rangachari L., Arn P., Cox G. F., Giugliani R., Okuyama T., Wijburg F., Kaplan P. Diagnosis and treatment trends in mucopolysaccharidosis I: findings from the MPS I Registry. Eur. J. Pediatr. 2012; 171: 911–919.

3. Platt F. M., Neises G. R., Reinkensmeier G., Townsend M. J., Perry V. H., Proia R. L., Winchester B., Dwek R. A., Butters T. D. Prevention of lysosomal storage in Tay-Sachs mice treated with N-butyldeoxynojirimycin. Science. 1997; 276: 428–431.

4. Jeyakumar M., Butters T. D., Cortina-Borja M., Hunnam V., Proia R. L., Perry V. H., Dwek R. A., Platt F. M. Delayed symptom onset and increased life expectancy in Sandhoff disease mice treated with N-butyldeoxynojirimycin. Proceed. Nat. Acad. Sci. USA. 1999; 96: 6388– 6393.

5. Andersson U., Smith D., Jeyakumar M., Butters T. D., Borja M. C., Dwek R. A., Platt F. M. Improved outcome of N-butyldeoxyga lactonojirimycin-mediated substrate reduction therapy in a mouse model of Sandhoff disease. Neurobiol. Dis. 2004; 16: 506–515.

6. Cox T., Lachmann R., Hollak C., Aerts J., Van Weely S., Hrebi cek M., Platt F., Butters T., Dwek R., Moyses C., Gow I., Elstein D., Zimran A. Novel oral treatment of Gaucher’s disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis. Lancet. 2000; 355: 1481–1485.

7. Piotrowska E., Jakobkiewicz-Banecka J., Baranska S., Tylki-Szymanska A., Czartoryska B., Wegrzyn A., Wegrzyn G. Genisteinmediated inhibition of glycosaminoglycan synthesis as a basis for gene expression-targeted isoflavone therapy for mucopolysaccharidoses. Eur. J. Hum. Genet. 2006; 14 (7): 846–852.

8. Kingma S. P., Wagemans T., Lilst L., Wijburq F. A., van Vlies N. Genistein increases glycosaminoglycan levels in mucopoly saccha ridosis type I cell models. J. Inherit. Metab. Dis. 2014; in press.

9. Kim K. H., Dodsworth C., Paras A., Burton B. K. High dose genistein aglycone therapy is safe in patients with mucopoly saccharidoses involving the central nervous system. Mol. Genet. Metab. 2013; 109 (4): 382–385.

10. Di Ferrante N., Nichols B. L., Knudson A. G., McCredie K. B., Singh J., Donnelly P. V. Mucopolysaccharide-storage diseases: corrective activity of normal human serum and lymphocyte extracts. Birth Defects. Orig. Article Ser. 1973; 9: 31–40.

11. Fratantoni J. C., Hall C. W., Neufeld E. F. Hurler and Hunter syndromes: mutual correction of the defect in cultured fibroblasts. Science. 1968; 162: 570–572.

12. Wiesmann U. N., Rossi E. E., Herschkowitz N. N. Treatment of metachromatic leukodystrophy in fibroblasts by enzyme replacement. New Engl. J. Med. 1971; 284: 672–673.

13. Kihara H., Porter M. T., Fluharty A. L. Enzyme replacement in cultured fibroblasts from metachromatic leukodystrophy. Birth Defects. Orig. Article Ser. 1973; 9: 19–26.

14. Church H., Tylee K., Cooper A., Thornley M., Mercer J., Wraith E., Carr T., O'Meara A., Wynn R. F. Biochemical monitoring after haemopoietic stem cell transplant for Hurler syndrome (MPSIH): implications for functional outcome after transplant in metabolic disease. Bone Marrow Transplant. 2007; 39: 207–210.

15. Souillet G., Guffon N., Maire I., Pujol M., Taylor P., Sevin F., Bleyzac N., Mulier C., Durin A., Kebaili K., Galambrun C., Bertrand Y., Froissart R., Dorche C., Gebuhrer L., Garin C., Berard J., Guibaud P. Outcome of 27 patients with Hurler's syndrome transplanted from either related or unrelated haematopoietic stem cell sources. Bone Marrow Transplant. 2003; 31: 1105–1117.

16. Vellodi A., Young E. P., Cooper A., Wraith J. E., Winchester B., Meaney C., Ramaswami U., Will A. bone marrow transplantation for mucopolysaccharidosis type I: experience of two British centres. Arch. Dis. Childhood. 1997; 76: 92–99.

17. Peters C., Shapiro E. G., Anderson J., Henslee-Downey P. J., Klemperer M. R., Cowan M. J., Saunders E. F., deAlarcon P. A., Twist C., Nachman J. B., Hale G. A., Harris R. E., Rozans M. K., Kurtzberg J., Grayson G. H., Williams T. E., Lenarsky C., Wagner J. E., Krivit W. Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. The Storage Disease Collaborative Study Group. Blood. 1998; 91: 2601–2608.

18. Vellodi A., Young E., Cooper A., Lidchi V., Winchester B., Wraith J. E. Long-term followup following bone marrow transplantation for Hunter disease. J. Inherit. Metab. Dis. 1999; 22 (5): 638–648.

19. Valayannopoulos V., Wijburg F. A. Therapy for the mucopolysaccharidoses. Rheumatology (Oxford). 2011; 50 (Suppl. 5): 49–59.

20. O’Brien J. S., Miller A. L., Loverde A. W., Veath M. L. Sanfilippo disease type B: enzyme replacement and metabolic correction in cultured fibroblasts. Science. 1973; 181: 753–755.

21. Desnick R. J., Schuchman E. H. Enzyme replacement therapy for lysosomal diseases: lessons from 20 years of experience and remaining challenges. Annu Rev. Genomics Hum. Genet. 2012; 13: 307–335. Doi: 10.1146/annurev-genom-090711-163739.

22. Vera M., Le S., Kan S. H., Garban H., Naylor D., Mlikotic A., Kaitila I., Harmatz P., Chen A., Dickson P. Immune response to intrathecal enzyme replacement therapy in mucopolysaccharidosis I patients. Pediatr. Res. 2013; 74 (6): 712–720.

23. Ehlert K., Frosch M., Fehse N., Zander A., Roth J., Vormoor J. Farber disease: clinical presentation, pathogenesis and a new approach to treatment. Pediatr. Rheum. Online J. 2007; 5: 15.

24. Simonaro C., Frohberg M., Ge Y., Menq F., Schuchman E. A 63: treatment of arthritis in animal models of the mucopolysaccharidosis using a novel anti-inflammatory drug, pentosan polysulfate. Arthritis Rheum. 2014; 66 (Suppl. 11): 93.

25. Ortolano S., Vieitez I., Navarro C., Spuch C. Treatment of lysosomal storage diseases: recent patents and future strategies. Rec. Pat. Endocr. Metab. Immune Drug Discov. 2014; 8 (1): 9–25.

26. Baldo G., Giuqliani R., Matte U. Gene delivery strategies for the treatment of mucopolysaccharidoses. Exp. Opin. Deliv. 2014; 11 (3): 449–59.