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Oral Zinc Sulphate Supplementation for Six Months in SCA2 Patients: A Randomized, Double-Blind, Placebo-Controlled Trial

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Abstract

Cuban patients with Spinocerebellar Ataxia type 2 (SCA2) have reduced concentrations of zinc in serum and cerebrospinal fluid (CSF). To assess the effect and safety of zinc supplementation, 36 Cuban SCA2 patients were randomly assigned to receive daily either 50 mg ZnSO4 or placebo, together with neurorehabilitation therapy in a randomized, double-blind, placebo-controlled clinical trial during 6 months. Outcome measures included the changes of zinc levels in CSF and serum, ataxia score, oxidative stress and saccadic eye movements. At the end of the study, the Zinc-treated group showed: (i) a significant increase of the Zn levels in the CSF, (ii) mild decrease in the ataxia scale subscores for gait, posture, stance and dysdiadochocinesia (iii) reduction of lipid’s oxidative damage, and (iv) reduction of saccadic latency when compared with the placebo group. The treatment was safe and well tolerated by all subjects. This study demonstrated the efficacy and safety of Zn supplementation, combined with neurorehabilitation for SCA2 patients and therefore it may encourage further studies on the clinical effect of zinc supplementation in SCA2 based in the conduction of future clinical trials with higher number of subjects.

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References

  1. Velázquez-Pérez L, Rodríguez-Labrada R, García-Rodríguez JC et al. (2011) Comprehensive review of spinocerebellar ataxia type 2. Cerebellum doi:10.1007/s12311-011-0265-2

  2. Velazquez Perez L, Cruz GS, Santos Falcon N et al (2009) Molecular epidemiology of spinocerebellar ataxias in Cuba: insights into SCA2 founder effect in Holguin. Neurosci Lett 454(2):157–160

    Article  PubMed  CAS  Google Scholar 

  3. Underwood BR, Rubinsztein DC (2008) Spinocerebellar ataxias caused by polyglutamine expansions: a review of therapeutic strategies. Cerebellum 7(2):215–221

    Article  PubMed  CAS  Google Scholar 

  4. Gonzalez C, Sánchez G, Quevedo AG et al (2005) Serum and cerebrospinal fluid levels of copper, iron and zinc in patiens with ataxia type SCA-2 from the province of Holguin in Cuba. Therapeutic Basic Dial Clin Neurosci 13(4):12–16

    Google Scholar 

  5. World Health Organization Committee (1996) Zinc. In: Trace elements in human nutrition and health. WHO, Geneva, pp 72–104

  6. Black MM (2003) The evidence linking zinc deficiency with children’s cognitive and motor functioning. J Nutr 133:1473S–1476S

    PubMed  CAS  Google Scholar 

  7. Wall MJ (2005) A role for zinc in cerebellar synaptic transmission? Cerebellum 4:224–229

    Article  PubMed  CAS  Google Scholar 

  8. Fosmire G (1990) Zn toxicity. Am J Clin Nutr 51:225–227

    PubMed  CAS  Google Scholar 

  9. Hooper PL, Visconti L, Garry PJ et al (1980) Zinc lowers high-density lipoprotein-cholesterol levels. J Am Med Assoc 244:1960–1961

    Article  CAS  Google Scholar 

  10. Haase H, Overbeck S, Rink L (2008) Zinc supplementation for the treatment or prevention of disease: Current status and future perspectives. Exp Gerontol 48:394–408

    Article  Google Scholar 

  11. Schmitz-Hubsch T, du Montcel ST, Baliko L et al (2006) Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology 66(11):1717–1720

    Article  PubMed  CAS  Google Scholar 

  12. Esterbaver H, Cheeseman K (1990) Determination of aldehydic lipid peroxidation product: Malondialdehyde and 4-hydroxynonenal. Meth Enzymol 186:407–421

    Article  Google Scholar 

  13. Erdelmeier I, Gerard D, Yadan J et al (1998) Reactions of N methyl-2-phenyl-indole with malondialdehyde and 4-hydroxialkenals. Mechanistic aspects of the colorimetric assay of lipid peroxidation. Chem Res Toxicol 11(10):1184–1194

    Article  PubMed  CAS  Google Scholar 

  14. Mannheim B (1987) Biochemica information. A revised biochemical reference source enzymes for routine, 1st edn. Boehringer Mannheim, Berlin, pp 15–16

    Google Scholar 

  15. Shukla G, Hussain T, Chandra S (1987) Possible role of superoxide dismutase activity and lipid peroxide levels in cadmium neurotoxicity: in vivo and in vitro studies in growing rats. Life Sci 14:2215–2225

    Article  Google Scholar 

  16. Witko-Sarsat V, Gausson V, Descamps-Latscha B (2003) Are advanced oxidation protein products potential uremic toxins? Kidney Int Suppl 84:S11–S14

    Article  PubMed  CAS  Google Scholar 

  17. Dvergsten CL, Fosmire GJ, Ollerich DA et al (1984) Alterations in the postnatal development of the cerebellar cortex due to zinc deficiency. II. Impaired maturation of Purkinje cells. Brain Res 318:11–20

    PubMed  CAS  Google Scholar 

  18. Dvergsten CL, Johnson LA, Sandstead HH (1984) Alterations in the postnatal development of the cerebellar cortex due to zinc deficiency. III. Impaired dendritic differentiation of basket and stellate cells. Brain Res 318:21–26

    PubMed  CAS  Google Scholar 

  19. Sensi SL, Paoletti P, Bush AI et al (2009) Zinc in the physiology and pathology of the CNS. Nat Rev Neurosci 10:780–791

    Article  PubMed  CAS  Google Scholar 

  20. Oteiza PI, Olin KL, Fraga CG et al (1995) Zinc deficiency causes oxidative damage to proteins, lipids and DNA in rat testes. J Nutr 125:823–829

    PubMed  CAS  Google Scholar 

  21. Mackenzie GG, Keen CL, Oteiza PI (2002) Zinc status of human IMR-32 neuroblastoma cells influences their susceptibility to iron-induced oxidative stress. Dev Neurosci 24:125–133

    Article  PubMed  CAS  Google Scholar 

  22. Mackenzie GG, Zago MP, Keen CL et al (2002) Low intracellular zinc impairs the translocation of activated NF-kB to the nuclei in human neuroblastoma IMR-32 cells. J Biol Chem 277:34610–34617

    Article  PubMed  CAS  Google Scholar 

  23. Bao B, Prasad A, Beck F et al (2010) Zinc decreases C-reactive protein, lipid peroxidation, and inflammatory cytokines in elderly subjects: a potential implication of zinc as an atheroprotective agent. Am J Clin Nutr 91(6):1634–1641

    Article  PubMed  CAS  Google Scholar 

  24. Farinati F, Cardin R, D’inca R et al (2003) Zinc treatment prevents lipid peroxidation and increases glutathione availability in Wilson’s disease. J Lab Clin Med 141(6):372–377

    Article  PubMed  CAS  Google Scholar 

  25. Marjani A (2005) Plasma lipid peroxidation zinc and erythrocyte Cu-Zn superoxide dismutase enzyme activity in patients with type 2 diabetes mellitus in Gorgan City (South East of the Caspian Sea). Internet J Endocrinol 2(1):1647–1648

    Google Scholar 

  26. Velazquez-Perez L, Seifried C, Santos-Falcon N et al (2004) Saccade velocity is controlled by polyglutamine size in spinocerebellar ataxia 2. Ann Neurol 56(3):444–447

    Article  PubMed  Google Scholar 

  27. Velazquez-Perez L, Seifried C, Abele M et al (2009) Saccade velocity is reduced in presymptomatic spinocerebellar ataxia type 2. Clin Neurophysiol 120(3):632–635

    Article  PubMed  CAS  Google Scholar 

  28. Buttner N, Geschwind D, Jen JC et al (1998) Oculomotor phenotypes in autosomal dominant ataxias. Arch Neurol 55(10):1353–1357

    Article  PubMed  CAS  Google Scholar 

  29. Rodríguez-Labrada R, Velázquez-Pérez L, Seigfried C et al. (2011) Saccadic latency is prolonged in spinocerebellar ataxia type 2 and correlates with the frontal-ecutive dysfunctions. J Neurol Sci doi:10.1016/j.jns.2011.03.033

  30. Hutton SB (2008) Cognitive control of saccadic eye movements. Brain Cogn 68(3):327–340

    Article  PubMed  CAS  Google Scholar 

  31. Agget P, Harries J (1979) Current status of zinc in health and disease states. Arch Dis Child 54:909–917

    Article  Google Scholar 

  32. Golub M, Takeuchi P, Keen C et al (1996) Activity and attention in zinc-deprived adolescent monkeys. Am J Clin Nutr 64(6):908–915

    PubMed  CAS  Google Scholar 

  33. Arnold LE, DiSilvestro RA (2005) Zinc in attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharm 15(4):619–627

    Article  Google Scholar 

Download references

Acknowledgment

We are grateful to the SCA2 patients, the Cuban Ministry of Health and the Iberoamerican multidisciplinary network for the movement disorders (RIBERMOV) for their cooperation.

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Authors and Affiliations

  1. Centro Para la Investigación y Rehabilitación de las Ataxias Hereditarias, Carretera Central Km 5 ½ Reparto Edecio Pérez, 80100, Holguín, Cuba

    Luis Velázquez-Pérez, Gilberto Sánchez-Cruz, Raúl Aguilera-Rodríguez, Roberto Rodríguez-Labrada, Julio Cesar Rodríguez-Díaz, Nalia Canales-Ochoa, Dennis Almaguer Gotay, Luis E. Almaguer Mederos, José M. Laffita Mesa & Consuelo González Triana

  2. Centro de Desarrollo e Investigación de Medicamentos, Habana, Cuba

    Jorge Rodríguez-Chanfrau, Marlene Porto-Verdecia, Orestes D. López-Hernandez & Iverlis Díaz Polanco

  3. Centro Para la Producción de Animales de Laboratorio, Habana, Cuba

    Julio Cesar García-Rodríguez

  4. Hospital Provincial de Medicina Natural y Tradicional, Holguín, Cuba

    Noemí Rodríguez Pupo

  5. Hospital Clínico-Quirúrgico “Lucia Iñiguez Landín”, Holguín, Cuba

    Idania Hidalgo Batista

  6. Instituto Nacional de Salud del Trabajo, Habana, Cuba

    Arelis Jayme Novas

Authors
  1. Luis Velázquez-Pérez
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  2. Jorge Rodríguez-Chanfrau
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  3. Julio Cesar García-Rodríguez
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  4. Gilberto Sánchez-Cruz
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  5. Raúl Aguilera-Rodríguez
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  6. Roberto Rodríguez-Labrada
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  7. Julio Cesar Rodríguez-Díaz
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  8. Nalia Canales-Ochoa
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  9. Dennis Almaguer Gotay
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  10. Luis E. Almaguer Mederos
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  11. José M. Laffita Mesa
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  12. Marlene Porto-Verdecia
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  13. Consuelo González Triana
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  14. Noemí Rodríguez Pupo
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  15. Idania Hidalgo Batista
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  16. Orestes D. López-Hernandez
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  17. Iverlis Díaz Polanco
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  18. Arelis Jayme Novas
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Corresponding author

Correspondence to Luis Velázquez-Pérez.

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Velázquez-Pérez, L., Rodríguez-Chanfrau, J., García-Rodríguez, J.C. et al. Oral Zinc Sulphate Supplementation for Six Months in SCA2 Patients: A Randomized, Double-Blind, Placebo-Controlled Trial. Neurochem Res 36, 1793–1800 (2011). https://doi.org/10.1007/s11064-011-0496-0

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  • DOI: https://doi.org/10.1007/s11064-011-0496-0

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