1.Effects of Senkyu-chacho-san on Motor Symptoms in Patients with Parkinson's Disease
Nami SHIZUMA ; Shin-ichi MURAMATSU ; Kunihiko IKEGUCHI ; Imaharu NAKANO
Kampo Medicine 2001;51(5):1087-1091
Senkyu-chacho-san (SC), an herbal medicine, can modulate striatal dopamine levels, but its effects on Parkinson's disease (PD) are unclear. To evaluate the efficacy, tolerance, and safety of SC in PD, 22 patients with idiopathic PD (aged 49 to 82 years; 13 women, staging Hoehen and Yahr 3 or 4) were given SC, 5.0 or 7.5g three times per day, for eight weeks. Existing antiparkinsonian drug regimes were kept unchanged. Motor functions were assessed based on the Unified Parkinson's Disease Rating Scale (UPDRS) at baseline and at weeks four and eight. After four weeks of SC administration, 14 patients showed a significant improvement in motor performance with respect to the motor scores of the UPDRS (p<0.05). The improvement in motor function declined slightly in four patients after eight weeks of treatment. No patients became worse in motor functions during treatment, and no serious adverse events occurred. This study suggests that SC is useful as an adjunct to dopaminergic drugs in PD.
2.Adeno-associated virus vector-mediated triple gene transfer of dopamine synthetic enzymes
Dongsheng FAN ; Yang SHEN ; Dexuan KANG ; Nakano IMAHARU ; Ozawa KEIYA
Chinese Medical Journal 2001;114(12):1276-1279
Objective To explore triple gene transfer of dopamine synthetic enzymes with separate adeno-associated virus (AAV) vectors.Methods The genes for dopamine synthetic enzymes, tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AADC), and GTP cyclohydrolase Ⅰ (GCH, an enzyme critical for tetrahydrobiopterin synthesis) were cotransduced into 293 cells with separate AAV vectors. Expressions of TH, AADC and GCH were detected by Western blot analysis. Intracellular dopamine level was assayed by high-performance liquid chromatography.Results TH, AADC and GCH were effectively coexpressed in transduced cells with three separate AAV vectors, AAV-TH, AAV-AADC and AAV-GCH. Furthermore, the coexpression resulted in an effectively spontaneous dopamine production in cotransduced cells.Conclusion The triple transduction of TH, AADC and GCH genes with separate AAV vectors is effective, which might be important to gene therapy for Parkinson's disease.
3.Cotransduction of tyrosine hydroxylase and aromatic L-amino acid decarboxylase genes into cultured striatal cells using adeno-associated virus vectors
Dongsheng FAN ; Dexuan KANG ; Ogawa MATSUO ; Nakano IMAHARU ; Nagatsu TOSHIHARU ; Kurtzman J. GARY ; Ozawa KEIYA
Chinese Medical Journal 1998;(12):1111-1113
Objective To examine whether tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) genes can be cotransduced into the same target striatal cells using adeno-associated virus (AAV) vectors, and to determine whether the cotransduction would result in better biochemical change than the TH gene alone.Methods TH and AADC genes were cotransduced into cultured striatal cells with separate AAV vectors. Expressions of TH and AADC were detected by immunocytochemistry; intracellular catecholamine levels were assayed by high-performance liquid chromatography (HPLC).Results TH and AADC genes were efficiently cotransduced into the striatal cells. Specifically, the coexpression of TH and AADC resulted in more effective dopamine production compared with the TH gene alone.Conclusion Using AAV vectors, coexpression of TH and AADC in the striatal cells might be a useful approach to gene therapy for Parkinson's disease.