Skip to main content
SpringerLink
Log in

Sulfamethoxazole-trimethoprim double-blind, placebo-controlled, crossover trial in Machado-Joseph disease: sulfamethoxazole-trimethoprim increases cerebrospinal fluid level of biopterin

  • Full Papers
  • Published:
Journal of Neural Transmission / General Section JNT Aims and scope Submit manuscript

Summary

We performed a double-blind, placebo-controlled, crossover trial of sulfamethoxazole-trimethoprim (S-T) in 8 patients with Machado-Joseph disease (MJD), and measured the blood and cerebrospinal fluid levels of biopterins, biogenic amines or metabolites, and folate. The clinical results were as follows; mild improvements of hyperreflexia of knee jerks and of rigospasticity of the legs during S-T treatment period. In addition, S-T significantly reduced the times of 8 motor activities on the timed tests. The biochemical results showed that basal levels of all biopterins and homovanillic acid in the cerebrospinal fluid (CSF) were reduced to less than half the levels of those of controls with other neurological diseases. After S-T treatment, total and oxidized form of biopterins in the CSF increased significantly. Therefore, S-T may be effective to neurologic deficits through its mechanism of increasing the level of brain biopterins.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Blau N, Heizmann CW, Sperl W, Korenke GC, Hoffmann GF, Smooker PM, Cotton RGH (1992) Atypical (mild) forms of dihydropteridine reductase deficiency: neurochemical evaluation and mutation detection. Pediatr Res 32: 726–730

    PubMed  Google Scholar 

  • Bredt DS, Hwang PM, Snyder SH (1990) Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature 347: 768–770

    PubMed  Google Scholar 

  • Burchall JJ (1973) Mechanism of action of trimethoprim-sulfamethoxazole II. J Infect Dis [Suppl] 128: 437–441

    Google Scholar 

  • Coutinho P, Andrade C (1978) Autosomal dominant system degeneration in Portuguese families of the Azores islands. Neurology 28: 703–709

    PubMed  Google Scholar 

  • Dahl H-HM, Hutchinson W, McAdam W, Wake S, Morgan FJ, Cotton RGH (1987) Human dihydropteridine reductase: characterisation of a cDNA clone and its use in analysis of patients with dihydropteridine reductase deficiency. Nucleic Acids Res 15: 1921–1932

    PubMed  Google Scholar 

  • Desaiah D, Joshi P, Vig PJS, Subramony SH, Currier RD (1994) Cerebellar nitric oxide synthase activity in patients with spinocerebellar ataxia-1 [abstract]. Neurology [Suppl 2] 44: 369–370

    Google Scholar 

  • Finch RG, Snyder IS (1990) Synthetic organic antimicrobials (sulfonamides, trimethoprim, nitrofurans, nalidixic acid, methenamine). In: Craig CR, Stitzel RE (eds) Modern pharmacology, 3rd ed. Little, Brown and Company, Boston, pp 642–653

    Google Scholar 

  • Fink JK, Barton N., Cohen W, Lovenberg W, Burns RS, Hallet M (1988) Dystonia with marked diurnal variation associated with biopterin deficiency. Neurology 38: 707–711

    PubMed  Google Scholar 

  • Fujishiro K, Hagihara M, Takahashi A, Nagatsu T (1990) Concentrations of neopterin and biopterin in the cerebrospinal fluid of patients with Parkinson's disease. Biochem Med Metab Biol 44: 97–100

    PubMed  Google Scholar 

  • Fukushima T, Nixon J (1980) Analysis of reduced forms of biopterin in biological tissues and fluids. Anal Biochem 102: 176–188

    PubMed  Google Scholar 

  • Furukawa Y, Kondo T, Nishi K, Yokochi F, Narabayashi H (1991) Total biopterin levels in the ventricular CSF of patients with Parkinson's disease: a comparison between akineto-rigid and tremor types. J Neurol Sci 103: 232–237

    PubMed  Google Scholar 

  • Grossman A, Rosenberg RN, Warmoth L (1987) Glutamate and malate dehydrogenase activities in Joseph disease and olivopontocerebellar atrophy. Neurology 37: 106–111

    PubMed  Google Scholar 

  • Kaufman S, Holtzman NA, Milstien S, Butler IJ, Krumholz A (1975) Phenylketonuria due to a deficiency of dihydropteridine reductase. N Engl J Med 293: 785–790

    PubMed  Google Scholar 

  • Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S, Kawakami H, Nakamura S, Nishimura M, Akiguchi I, Kimura J, Narumiya S, Kakizuka A (1994) CAG expansions in a novel gene from Machado-Joseph disease at chromosome 14q32.1. Nature Genet 8: 221–228

    PubMed  Google Scholar 

  • Kay AD, Milstien S, Kaufman S, Creasey H, Haxby JV, Cutler NR, Rapoport SI (1986) Cerebrospinal fluid biopterin is decreased in Alzheimer's disease. Arch Neurol 43: 996–999

    PubMed  Google Scholar 

  • Komori H, Matsuishi T, Yamada S, Ichikawa K, Amamoto M, Yamashita F (1994) Elevated biopterin and homovanillic acid levels in cerebrospinal fluid from children with aseptic meningitis. J Child Neurol 9: 22–25

    PubMed  Google Scholar 

  • Koshimura K, Miwa S, Lee K, Fujiwara M, Watanabe Y (1990) Enhancement of dopamine elease in vivo from the rat striatum by dialytic perfusion of 6R-L-erythro-5,6,7,8- tetrahydrobiopterin. J Neurochem 54: 1391–1397

    PubMed  Google Scholar 

  • Lockyer J, Cook RG, Milstien S, Kaufman S, Woo SL, Ledley FD (1987) Structure and expression of human dihydropteridine reductase. Proc Natl Acad Sci USA 84: 3329–3333

    PubMed  Google Scholar 

  • Mataga N, Imamura K, Watanabe Y (1991) 6R-Tetrahydrobiopterin perfusion enhances dopamine, serotonin and glutamate outputs in dialysate from rat striatum and frontal cortex. Brain Res 551: 64–71

    PubMed  Google Scholar 

  • Mello KA, Abbott BP (1988) Effect of sulfamethoxazole and trimethoprim on neurologic dysfunctions in a patient with Joseph's disease. Arch Neurol 45: 210–213

    PubMed  Google Scholar 

  • Moncada S, Higgs A (1993) Mechanism of disease: the L-arginine-nitric oxide pathway. N Engl J Med 329: 2002–2012

    PubMed  Google Scholar 

  • Nagatsu T, Horikoshi T, Sawada M, Nagatsu I, Kondo T, Iizuka R, Narabayashi H (1986) Biosynthesis of tetrahydrobiopterin in parkinsonian human brain. In: Yahr MD, Bergmann KJ (eds) Advances in neurology, vol 45. Raven Press, New York, pp 223–226

    Google Scholar 

  • Nakano KK, Dawson DM, Spence A (1972) Machado disease: a hereditary ataxia in Portuguese emigrants to Massachusette. Neurology 22: 49–55

    PubMed  Google Scholar 

  • Niederwieser A, Blau N, Wang M, Joller P, Atarés Cardesa-Garcia J (1984) GTP cyclohydrolase I deficiency, a new enzyme defect causing hyperphenyl-alaninemia with neopterin, biopterin, dopamine, and serotonin deficiencies and muscular hypotonia. Eur J Pediatr 141: 208–214

    PubMed  Google Scholar 

  • Noro H, Minami R (1992) Effects of combination of sulfamethoxazole and trimethoprim on cerebellar ataxia and spasticity in a patient with Joseph's diesase type II. Neurol Ther 9: 279–283 (English abstract)

    Google Scholar 

  • Nunokawa Y, Ishihara T, Kanai T, Noguchi T (1992) (6R)-5,6,7,8-tetrahydro-L-biopterin modulates nitric oxide-associated soluble guanylate cyclase activity in the rat cerebellum. Arch Biochem Biophys 298: 726–730

    PubMed  Google Scholar 

  • Ohue T, Koshimura K, Takagi Y, Watanabe Y, Miwa S, Masaki T (1993) Enhancement of acetylcholine release in the hippocampus by 6R-L-erythro-5,6,7,8-tetrahydrobiopterin is mediated by 5-hydroxytryptamine. Brain Res 607: 255–260

    PubMed  Google Scholar 

  • Ratnam S, Ratnam M, Cotton RGH, Jennings IG, Freisheim JH (1989) Anti-idiotypic antibodies elicited by pterin recognize active site epitopes in dihydrofolate reductases and dihydropteridine reductase. Arch Biochem Biophys 275: 344–353

    PubMed  Google Scholar 

  • Rosenberg RN (1991) Joseph disease: an autosomal dominant motor system degeneration. In: de Jong JN (ed) Handbook of clinical neurology, revised series. Hereditary neuropathies and spinocerebellar atrophies, vol 16(60). Elsevier, New York, pp 467–479

    Google Scholar 

  • Rosenberg RN, Thomas L, Baskin F, Kirkpatrick J, Bay C, Nyhan WL (1979) Joseph disease: protein patterns in fibroblasts and brain. Neurology 29: 917–926

    PubMed  Google Scholar 

  • Sakai T, Ohta M, Ishino H (1983) Joseph disease in a non-Portuguese family. Neurology 33: 74–80

    PubMed  Google Scholar 

  • Sakai T (1989) Clinical characteristics of Joseph disease. A proposal of diagnostic criteria. Neurol Med (Tokyo) 30: 246–252 (in Japanese)

    Google Scholar 

  • Sakai T, Oda K (1993) Abundant reinnervation in peripheral nerves in Joseph disease. Neurology 43: 428–430

    PubMed  Google Scholar 

  • Sangla S, Broucker TD, Cheron F, Cambier J, Dehen H (1990) Amélioration d'une maladie de Joseph par le sulfaméthoxazole-triméthoprim. Rev Neurol (Paris) 146: 213–214

    Google Scholar 

  • Sawada M, Hirata Y, Arai H, Iizuka R, Nagatsu T (1987) Tyrosine hydroxylase, tryptophan hydroxylase, biopterin, and neopterin in the brains of normal controls and patients with senile dementia of Alzheimer type. J Neurochem 48: 760–764

    PubMed  Google Scholar 

  • Shintaku H, Niederwieser A, Leimbacher W, Curtius HC (1988) Tetrahydrobiopterin deficiency: assay for 6-pyruvoyl-tetrahydropterin synthase activity in erythrocytes, and detection of patients and heterozygous carriers. Eur J Pediatr 147: 15–19

    PubMed  Google Scholar 

  • Spinella GM, Sheridan PH (1992) Research initiatives on Machado-Joesph disease: National Institute of Neurological Disorders and Stroke workshop summary. Neurology 42: 2048–2051

    PubMed  Google Scholar 

  • Takiyama Y, Nishizawa M, Tanaka H, Kawashima S, Sakamoto H, Karube Y, Shimazaki H, Soutome M, Endo K, Ohta S, Kagawa Y, Kanazawa I, Mizuno Y, Yoshida M, Yuasa T, Horikawa Y, Oyanagi K, Nagai H, Kondo T, Inuzuka T, Onodera O, Tsuji S (1993) The gene for Machado-Joseph disease maps to human chromosome 14q. Nature Genet 4: 300–304

    PubMed  Google Scholar 

  • Takiyama Y, Hanyu S, Niijima K, Mizuno Y, Yoshida M (1990) Effect of sulfamethoxazole and trimethoprim (BactaR) on Machado-Joseph disease: a doubleblind, placebo-controlled trial. Neurol Med (Tokyo) 32: 594–600 (English abstract)

    Google Scholar 

  • Woods BT, Schaumburg HH (1972) Nigro-spino-dentatal degeneration with nuclear ophthalmoplegia: an unique and partially treatable clinicopathological entity. J Neurol Sci 17: 149–166

    PubMed  Google Scholar 

  • Yokoo H, Kojima H, Yamada S, Tsutsumi T, Anno N, Anraku S, Nishi S, Inanaga K (1990) Simultaneous determination of dopamine, serotonin, 3,4-dihydroxy-phenyl-acetic acid, homovanillic acid, 3-methoxytyramine and 5-hydroxyindole-3-acetic acid by high performance liquid chromatography with electrochemical detection. Kurume Med J 32: 75–80

    Google Scholar 

Download references

Author information

Author notes

  1. T. Sakai

    Present address: Department of Neurology, National Chikugo Hospital, Fukuoka

Authors and Affiliations

  1. Department of Neurology, National Chikugo Hospital, Fukuoka

    H. Iwashita

  2. Department of Pediatrics and Child Health, Kurume University School of Medicine, Fukuoka

    T. Matsuishi & H. Komori

  3. Institute of Brain Diseases, Kurume University School of Medicine, Fukuoka, Japan

    S. Yamada

Authors
  1. T. Sakai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Matsuishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Komori
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. Iwashita
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sakai, T., Matsuishi, T., Yamada, S. et al. Sulfamethoxazole-trimethoprim double-blind, placebo-controlled, crossover trial in Machado-Joseph disease: sulfamethoxazole-trimethoprim increases cerebrospinal fluid level of biopterin. J. Neural Transmission 102, 159–172 (1995). https://doi.org/10.1007/BF01276511

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01276511

Keywords

Search

Navigation