Tetrahydrobiopterin and Parkinson's disease

Abstract

Two patients with Parkinson's disease were treated with 1 g tetrahydrobiopterin (BH4) for 5 days. Clinical improvement was not observed. In the cerebrospinal fluid (CSF) a 4-8 fold increase in the concentration of homovanillic acid (HVA), and a 3-fold increase in the concentration of 5-hydroxyindole acetic acid (5-HIAA) was measured. However, the concentration of HVA reached, was only approximately half as high, as that of patients treated with madopar (DOPA + benserazid). In urine, the excretion of HVA increased 13-37 fold, when the patients were treated with madopar, whereas no increase in the HVA excretion was measured after the BH4 administration. Additionally, 2 patients with Parkinson's disease were treated with 1 g BH4 in combination with 15 g tyrosine for 3 days, and 1 parkinsonian patient was treated with 15 g tyrosine daily for 7 weeks. No increase in the CSF concentrations of HVA or 5-HIAA was observed. The results suggest, the BH4 in the dosage used, is not effective in the treatment of Parkinson's disease.

Effect of age on cerebrospinal fluid levels of metabolites of biopterin and biogenic amines

“…This may be due to differences in methods and procedures. In other studies, biopterin and biogenic amine metabolites were not simultaneously evaluated (2-6, 8, 13), the control pa-tients had neurological diseases (2,6,8), the patients' conditions were not described in detail (2-5, 8, 13) or there was a relatively small number of patients (2)(3)(4)(5)(6)13).…”

“…It has recently been discovered that the level of biopterin in cerebrospinal fluid (CSF) is altered in many neurological disorders, i.e. decreased in phenylketonuria due to biopterin deficiency (1), Parkinson's disease (2,3), Alzheimer's disease (4), depression (1), hereditary progressive dystonia with marked diurnal fluctuation (5) and autistic behaviour (6); and increased in inflammation of the central nervous system in the acute phase (1,7) and in Rett syndrome (8).…”

Cerebrospinal fluid biochemical studies in patients with Parkinson's disease: toward a potential search for biomarkers for this disease

“…Amantadine did not change HVA levels (Cox et al, 1973). Tetrahydrobiopterin (Dissing et al, 1989) and L-threo-3,4-dihydroxyphenylserine (precursor or noraderenalin or norepinephrine –NE) (Maruyama et al, 1994) increased CSF HVA levels in PD patients, but to a lesser extent than levodopa.…”

“…Gumpert et al (1973) described an association between relatively low pre-treatment CSF 5-HIAA levels with a good response to levodopa, while Davidson et al (1977) reported this association with higher CSF 5-HIAA levels, and others found no such relation (Granerus et al, 1974). Tetrahydrobiopterin increased (Dissing et al, 1989), and L-threo-3,4-dihydroxyphenylserine decreased (Maruyama et al, 1994) CSF 5-HIAA levels.…”

In Vivo Determination of Tetrahydrobiop- terin and Monoamine Neurotransmitters in Rat Brain by Liquid Chromatography with a Nano Crystalline Mn-Doped Lead Dioxide Film Modified Electrode

“…Early research showed that peripherally administered BH 4 do enter the brain [5] and increase the concentration of some neurotransmitters in the brain [6]. It has also been reported that the administration of BH 4 can improve the clinical symptoms of some diseases which are caused by abnormal monoamine metabolism, such as Parkinson's disease [7] and depression [8]. The relationship between BH 4 and monoamine neurotransmitters [9] can be described as in Fig.…”