Recommendations on Clinical Trial Design for Treatment of Mucopolysaccharidosis Type III

Overview

Journal Orphanet J Rare Dis

Publisher Biomed Central

Specialty General Medicine

Date 2017 Jun 28

PMID 28651568

Citations 14

Authors

Arunabha Ghosh

Elsa Shapiro

Stewart Rust

Kathleen Delaney

Samantha Parker

Adam J Shaywitz

Adelaida Morte

Gillian Bubb

Maureen Cleary

Tien Bo

Christine Lavery

Brian W Bigger

Simon A Jones

Affiliations

Soon will be listed here.

Abstract

Background: Mucopolysaccharidosis type III is a progressive, neurodegenerative lysosomal storage disorder for which there is currently no effective therapy. Though numerous potential therapies are in development, there are several challenges to conducting clinical research in this area. We seek to make recommendations on the approach to clinical research in MPS III, including the selection of outcome measures and trial endpoints, in order to improve the quality and impact of research in this area.

Results: An international workshop involving academic researchers, clinical experts and industry groups was held in June 2015, with presentations and discussions on disease pathophysiology, biomarkers, potential therapies and clinical outcome measures. A set of recommendations was subsequently prepared by a working group and reviewed by all delegates. We present a series of 11 recommendations regarding the conduct of clinical research, outcome measures and management of natural history data in Mucopolysaccharidosis type III.

Conclusions: Improving the quality of clinical research in Mucopolysaccharidosis type III will require an open, collaborative and systematic approach between academic researchers, clinicians and industry. Natural history data should be published as soon as possible and ideally collated in a central repository. There should be agreement on outcome measures and instruments for evaluation of clinical outcomes to maximise the effectiveness of current and future clinical research.

Citing Articles

Anakinra in Sanfilippo syndrome: a phase 1/2 trial.

Polgreen L, Chen A, Pak Y, Luzzi A, Morales Garval A, Acevedo J Nat Med. 2024; 30(9):2473-2479.

PMID: 38907160 PMC: 11405265. DOI: 10.1038/s41591-024-03079-3.

Intraparenchymal convection enhanced delivery of AAV in sheep to treat Mucopolysaccharidosis IIIC.

OLeary C, Forte G, Mitchell N, Youshani A, Dyer A, Wellby M J Transl Med. 2023; 21(1):437.

PMID: 37407981 PMC: 10320977. DOI: 10.1186/s12967-023-04208-1.

Economic Burden of Sanfilippo Syndrome in the United States.

Ashby F, Park H, Svensson M, Heldermon C Res Sq. 2023; .

PMID: 37398464 PMC: 10312916. DOI: 10.21203/rs.3.rs-3001450/v1.

GENE TARGET: A framework for evaluating Mendelian neurodevelopmental disorders for gene therapy.

Chopra M, Modi M, Dies K, Chamberlin N, Buttermore E, Brewster S Mol Ther Methods Clin Dev. 2022; 27:32-46.

PMID: 36156879 PMC: 9478871. DOI: 10.1016/j.omtm.2022.08.007.

Increasing precision in the measurement of change in pediatric neurodegenerative disease.

Eisengart J, Daniel M, Adams H, Williams P, Kuca B, Shapiro E Mol Genet Metab. 2022; 137(1-2):201-209.

PMID: 36115283 PMC: 9879307. DOI: 10.1016/j.ymgme.2022.09.001.

References

Fraser J, Gason A, Wraith J, Delatycki M . Sleep disturbance in Sanfilippo syndrome: a parental questionnaire study. Arch Dis Child. 2005; 90(12):1239-42. PMC: 1720229. DOI: 10.1136/adc.2004.065482. View

de Ruijter J, Maas M, Janssen A, Wijburg F . High prevalence of femoral head necrosis in Mucopolysaccharidosis type III (Sanfilippo disease): a national, observational, cross-sectional study. Mol Genet Metab. 2013; 109(1):49-53. DOI: 10.1016/j.ymgme.2013.03.004. View

Wynn R, Wraith J, Mercer J, OMeara A, Tylee K, Thornley M . Improved metabolic correction in patients with lysosomal storage disease treated with hematopoietic stem cell transplant compared with enzyme replacement therapy. J Pediatr. 2009; 154(4):609-11. DOI: 10.1016/j.jpeds.2008.11.005. View

Zhang H, Wood T, Young S, Millington D . A straightforward, quantitative ultra-performance liquid chromatography-tandem mass spectrometric method for heparan sulfate, dermatan sulfate and chondroitin sulfate in urine: an improved clinical screening test for the mucopolysaccharidoses. Mol Genet Metab. 2014; 114(2):123-8. DOI: 10.1016/j.ymgme.2014.09.009. View

Martin H, Poe M, Reinhartsen D, Pretzel R, Roush J, Rosenberg A . Methods for assessing neurodevelopment in lysosomal storage diseases and related disorders: a multidisciplinary perspective. Acta Paediatr. 2008; 97(457):69-75. DOI: 10.1111/j.1651-2227.2008.00651.x. View

Wilkinson F, Holley R, Langford-Smith K, Badrinath S, Liao A, Langford-Smith A . Neuropathology in mouse models of mucopolysaccharidosis type I, IIIA and IIIB. PLoS One. 2012; 7(4):e35787. PMC: 3338781. DOI: 10.1371/journal.pone.0035787. View

Naimy H, Powell K, Moriarity J, Wu J, McCauley T, Haslett P . A novel LC-MS/MS assay for heparan sulfate screening in the cerebrospinal fluid of mucopolysaccharidosis IIIA patients. Bioanalysis. 2016; 8(4):285-95. DOI: 10.4155/bio.15.243. View

Prinsen C, Vohra S, Rose M, King-Jones S, Ishaque S, Bhaloo Z . Core Outcome Measures in Effectiveness Trials (COMET) initiative: protocol for an international Delphi study to achieve consensus on how to select outcome measurement instruments for outcomes included in a 'core outcome set'. Trials. 2014; 15:247. PMC: 4082295. DOI: 10.1186/1745-6215-15-247. View

Zafeiriou D, Sewell A, Papadopoulou F, Badouraki M, Vargiami E, Gombakis N . Serial magnetic resonance imaging findings in mucopolysaccharidosis IIIB (Sanfilippo's syndrome B). Brain Dev. 2001; 23(6):385-9. DOI: 10.1016/s0387-7604(01)00242-x. View

10.

Grant S, Cross E, Wraith J, Jones S, Mahon L, Lomax M . Parental social support, coping strategies, resilience factors, stress, anxiety and depression levels in parents of children with MPS III (Sanfilippo syndrome) or children with intellectual disabilities (ID). J Inherit Metab Dis. 2012; 36(2):281-91. DOI: 10.1007/s10545-012-9558-y. View

11.

Delgadillo V, Del Mar OCallaghan M, Artuch R, Montero R, Pineda M . Genistein supplementation in patients affected by Sanfilippo disease. J Inherit Metab Dis. 2011; 34(5):1039-44. DOI: 10.1007/s10545-011-9342-4. View

12.

Verhoeven W, Csepan R, Marcelis C, Lefeber D, Egger J, Tuinier S . Sanfilippo B in an elderly female psychiatric patient: a rare but relevant diagnosis in presenile dementia. Acta Psychiatr Scand. 2009; 122(2):162-5. DOI: 10.1111/j.1600-0447.2009.01521.x. View

13.

Malinowska M, Wilkinson F, Langford-Smith K, Langford-Smith A, Brown J, Crawford B . Genistein improves neuropathology and corrects behaviour in a mouse model of neurodegenerative metabolic disease. PLoS One. 2010; 5(12):e14192. PMC: 2995736. DOI: 10.1371/journal.pone.0014192. View

14.

de Ru M, van der Tol L, van Vlies N, Bigger B, Hollak C, Ijlst L . Plasma and urinary levels of dermatan sulfate and heparan sulfate derived disaccharides after long-term enzyme replacement therapy (ERT) in MPS I: correlation with the timing of ERT and with total urinary excretion of glycosaminoglycans. J Inherit Metab Dis. 2012; 36(2):247-55. DOI: 10.1007/s10545-012-9538-2. View

15.

Heldermon C, Qin E, Ohlemiller K, Herzog E, Brown J, Vogler C . Disease correction by combined neonatal intracranial AAV and systemic lentiviral gene therapy in Sanfilippo Syndrome type B mice. Gene Ther. 2013; 20(9):913-21. PMC: 3701029. DOI: 10.1038/gt.2013.14. View

16.

Zhang H, Young S, Auray-Blais C, Orchard P, Tolar J, Millington D . Analysis of glycosaminoglycans in cerebrospinal fluid from patients with mucopolysaccharidoses by isotope-dilution ultra-performance liquid chromatography-tandem mass spectrometry. Clin Chem. 2011; 57(7):1005-12. DOI: 10.1373/clinchem.2010.161141. View

17.

Delaney K, Rudser K, Yund B, Whitley C, Haslett P, Shapiro E . Methods of neurodevelopmental assessment in children with neurodegenerative disease: Sanfilippo syndrome. JIMD Rep. 2013; 13:129-37. PMC: 4110329. DOI: 10.1007/8904_2013_269. View

18.

Dickson P, Pariser A, Groft S, Ishihara R, McNeil D, Tagle D . Research challenges in central nervous system manifestations of inborn errors of metabolism. Mol Genet Metab. 2010; 102(3):326-38. PMC: 3040279. DOI: 10.1016/j.ymgme.2010.11.164. View

19.

Emre S, Terzioglu M, Tokatli A, Coskun T, Ozalp I, Weber B . Sanfilippo syndrome in Turkey: Identification of novel mutations in subtypes A and B. Hum Mutat. 2002; 19(2):184-5. DOI: 10.1002/humu.9009. View

20.

Kim K, Dodsworth C, Paras A, Burton B . High dose genistein aglycone therapy is safe in patients with mucopolysaccharidoses involving the central nervous system. Mol Genet Metab. 2013; 109(4):382-5. DOI: 10.1016/j.ymgme.2013.06.012. View