Randomized, double-blind, placebo-controlled trial of hydroxyurea in spinal muscular atrophy

Neurology

Volumn 75, Issue 24, 2010, Pages 2190-2197

  Chen, T H ^a,b,c   Chang, J G ^b,d   Yang, Y H ^e   Mai, H H ^a   Liang, W C ^a   Wu, Y C ^f   Wang, H Y ^f   Huang, Y B ^g   Wu, S M ^g   Chen, Y C ^c   Yang, S N ^a,c   Jong, Y J ^a,b,c  

^a Department of Emergency   (Taiwan)

^b KAOHSIUNG MEDICAL UNIVERSITY HOSPITAL   (Taiwan)

^c Graduate Institute of Medicine   (Taiwan)

^d Institute of Clinical Pharmacy and Pharmaceutical Sciences   (Taiwan)

^e Faculty of Dentistry   (Taiwan)

^f Department of Physical Therapy   (Taiwan)

^g KAOHSIUNG MEDICAL UNIVERSITY   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

HYDROXYUREA; MESSENGER RNA; PLACEBO;

ADOLESCENT; ADULT; AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; ASTHMA; CHILD; CLINICAL ARTICLE; DOUBLE BLIND PROCEDURE; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG ERUPTION; DRUG SAFETY; FEMALE; FORCED VITAL CAPACITY; GASTROINTESTINAL DISEASE; GASTROINTESTINAL INFECTION; GROSS MOTOR FUNCTION MEASURE; HUMAN; MALE; MOTOR PERFORMANCE; NEUROLOGIC DISEASE; NEUTROPENIA; PHASE 2 CLINICAL TRIAL; PHASE 3 CLINICAL TRIAL; PNEUMONIA; PRESCHOOL CHILD; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RESPIRATORY FAILURE; RESPIRATORY TRACT DISEASE; SCHOOL CHILD; SIDE EFFECT; SPINAL MUSCULAR ATROPHY; THROMBOCYTOPENIA; TREATMENT OUTCOME; UNSPECIFIED SIDE EFFECT; URINARY TRACT INFECTION;

ADOLESCENT; ADULT; CHILD; CHILD, PRESCHOOL; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; FOLLOW-UP STUDIES; HUMANS; HYDROXYUREA; MALE; MOTOR ACTIVITY; MOTOR NEURONS; MUSCULAR ATROPHY, SPINAL; NEUTROPENIA; NUCLEIC ACID SYNTHESIS INHIBITORS; RNA, MESSENGER; TREATMENT FAILURE; VITAL CAPACITY; YOUNG ADULT;

EID: 78650809695     PISSN: 00283878     EISSN: 1526632X     Source Type: Journal    
DOI: 10.1212/WNL.0b013e3182020332     Document Type: Article

References (33)

1. Crawford TO, Pardo CA. The neurobiology of childhood spinal muscular atrophy. Neurobiol Dis 1996;3:97-110.
2. Lunn MR, Wang CH. Spinal muscular atrophy. Lancet 2008;371:2120-2133.
3. Lefebvre S, Burglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell 1995;80:155-165.
4. Lorson CL, Hahnen E, Androphy EJ, Wirth B. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc Natl Acad Sci USA 1999;96:6307-6311.
5. Campbell L, Potter A, Ignatius J, et al. Genomic variation and gene conversion in spinal muscular atrophy: implications for disease process and clinical phenotype. Am J Hum Genet 1997;61:40-50.
6. Hsieh-Li HM, Chang JG, Jong YJ, et al. A mouse model for spinal muscular atrophy. Nat Genet 2000;24:66-70.
7. Chang JG, Hsieh-Li HM, Jong YJ, et al. Treatment of spinal muscular atrophy by sodium butyrate. Proc Natl Acad Sci USA 2001;98:9808-9813.
8. Hirtz D, Iannaccone S, Heemskerk J, et al. Challenges and opportunities in clinical trials for spinal muscular atrophy. Neurology 2005;65:1352-1357.
9. Burnett BG, Crawford TO, Sumner CJ. Emerging treatment options for spinal muscular atrophy. Curr Treat Options Neurol 2009;11:90-101.
10. Steinberg MH, Barton F, Castro O, et al. Effect of hy-droxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment. JAMA 2003;289:1645-1651.
11. Platt OS. Hydroxyurea for the treatment of sickle cell anemia. N Engl J Med 2008;358:1362-1369.
12. Chang JG, Jong YJ, Tsai FJ, inventors; China Medical College Hospital, assignee. Hydroxyurea treatment for spinal muscular atrophy. US Patent 6,573,300. June 3, 2003.
13. Beckloff GL, Lerner HJ, Frost D, et al. Hydroxyurea (NSC-32065) in biologic fluids: dose-concentration relationship. Cancer Chemother Rep 1965;48:57-58.
14. Strouse JJ, Lanzkron S, Beach MC, et al. Hydroxyurea for sickle cell disease: a systematic review for efficacy and tox-icity in children. Pediatrics 2008;122:1332-1342.
15. Liang WC, Yuo CY, Chang JG, et al. The effect of hy-droxyurea in spinal muscular atrophy cells and patients. J Neurol Sci 2008;268:87-94.
16. Munsat TL, Davies KE. International SMA Consortium meeting. (26-28 June 1992, Bonn, Germany). Neuro-muscul Disod 1992;2:423-428.
17. Zimmerman SA, Schultz WH, Davis JS, et al. Sustained long-term hematologic efficacy of hydroxyurea at maximum tolerated dose in children with sickle cell disease. Blood 2004;103:2039-2045.
18. Nelson L, Owens H, Hynan LS, Iannaccone ST. The gross motor function measure is a valid and sensitive outcome measure for spinal muscular atrophy. Neuromuscul Disord 2006;16:374-380.
19. Wang HY, Yang YH, Jong YJ. Evaluation of muscle strength in patients with spinal muscular atrophy. Kaohsi-ung J Med Sci 2002;18:241-247.
20. Krosschell KJ, Maczulski JA, Crawford TO, et al. A modified Hammersmith functional motor scale for use in multi-center research on spinal muscular atrophy. Neuromuscul Disord 2006;16:417-426.
21. Simard LR, Belanger MC, Morissette S, et al. Preclinical validation of a multiplex real-time assay to quantify SMN mRNA in patients with SMA. Neurology 2007;68:451-456.
22. Jong YJ, Hsu HO, Wu HL, et al. Analysis of hydroxyurea in human plasma by high performance liquid chromatog-raphy with electrochemical detection. Anal Chim Acta 2003;488:223-230.
23. Grzeschik SM, Ganta M, Prior TW, et al. Hydroxyurea enhances SMN2 gene expression in spinal muscular atrophy cells. Ann Neurol 2005;58:194-202.
24. Tsai LK, Yang CC, Ting CH, et al. Correlation of survival motor neuron expression in leukocytes and spinal cord in spinal muscular atrophy. J Pediatr 2009;154:303-305.
25. Brahe C, Vitali T, Tiziano FD, et al. Phenylbutyrate increases SMN gene expression in spinal muscular atrophy patients. Eur J Hum Genet 2005;13:256-259.
26. Swoboda KJ, Scott CB, Reyna SP, et al. Phase II open label study of valproic acid in spinal muscular atrophy. PLoS ONE 2009;4:e5268.
27. Gwilt PR, Tracewell WG. Pharmacokinetics and pharmacody-namics of hydroxyurea. Clin Pharmacokinet 1998;34:347-358.
28. Ware RE, Eggleston B, Redding-Lallinger R, et al. Predictors of fetal hemoglobin response in children with sickle cell anemia receiving hydroxyurea therapy. Blood 2002;99:10-14.
29. Mercuri E, Bertini E, Messina S, et al. Randomized, double-blind, placebo-controlled trial of phenylbutyrate in spinal muscular atrophy. Neurology 2007;68:51-55.
30. Swoboda KJ, Kissel JT, Crawford TO, et al. Perspectives on clinical trials in spinal muscular atrophy. J Child Neu-rol 2007;22:957-966.
31. Iannaccone ST, Russman BS, Browne RH, et al. Prospective analysis of strength in spinal muscular atrophy: DCN/ Spinal Muscular Atrophy Group. J Child Neurol 2000;15: 97-101.
32. Schroth MK. Special considerations in the respiratory management of spinal muscular atrophy. Pediatrics 2009; 123:S245-S249.
33. Steffensen BF, Lyager S, Werge B, et al. Physical capacity in non-ambulatory people with Duchenne muscular dystrophy or spinal muscular atrophy: a longitudinal study. Dev Med Child Neurol 2002;44:623-632.