TY  - JOUR
A1  - Gerlach, Manfred
A1  - Maetzler, Walter
A1  - Broich, Karl
A1  - Hampel, Harald
A1  - Rems, Lucas
A1  - Reum, Torsten
A1  - Riederer, Peter
A1  - Stäffler, Albrecht
A1  - Streffer, Johannes
A1  - Berg, Daniela
T1  - Biomarker candidates of neurodegeneration in Parkinson's disease for the evaluation of disease-modifying therapeutics
JF  - Journal of Neural Transmission
N2  - Reliable biomarkers that can be used for early diagnosis and tracking disease progression are the cornerstone of the development of disease-modifying treatments for Parkinson’s disease (PD). The German Society of Experimental and Clinical Neurotherapeutics (GESENT) has convened a Working Group to review the current status of proposed biomarkers of neurodegeneration according to the following criteria and to develop a consensus statement on biomarker candidates for evaluation of disease-modifying therapeutics in PD. The criteria proposed are that the biomarker should be linked to fundamental features of PD neuropathology and mechanisms underlying neurodegeneration in PD, should be correlated to disease progression assessed by clinical rating scales, should monitor the actual disease status, should be pre-clinically validated, and confirmed by at least two independent studies conducted by qualified investigators with the results published in peer-reviewed journals. To date, available data have not yet revealed one reliable biomarker to detect early neurodegeneration in PD and to detect and monitor effects of drug candidates on the disease process, but some promising biomarker candidates, such as antibodies against neuromelanin, pathological forms of α-synuclein, DJ-1, and patterns of gene expression, metabolomic and protein profiling exist. Almost all of the biomarker candidates were not investigated in relation to effects of treatment, validated in experimental models of PD and confirmed in independent studies.
KW  - disease progression
KW  - biomarkers
KW  - neuroprotection
KW  - disease-modifying therapies
KW  - Parkinson’s disease
KW  - surrogate endpoints
KW  - drug development
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125375
VL  - 119
IS  - 1
ER  - 
TY  - JOUR
A1  - Capetian, Philipp
A1  - Roessner, Veit
A1  - Korte, Caroline
A1  - Walitza, Susanne
A1  - Riederer, Franz
A1  - Taurines, Regina
A1  - Gerlach, Manfred
A1  - Moser, Andreas
T1  - Altered urinary tetrahydroisoquinoline derivatives in patients with Tourette syndrome: reflection of dopaminergic hyperactivity?
JF  - Journal of Neural Transmission
N2  - Tetrahydroisoquinolines (TIQs) such as salsolinol (SAL), norsalsolinol (NSAL) and their methylated derivatives N-methyl-norsalsolinol (NMNSAL) and N-methyl-salsolinol (NMSAL), modulate dopaminergic neurotransmission and metabolism in the central nervous system. Dopaminergic neurotransmission is thought to play an important role in the pathophysiology of chronic tic disorders, such as Tourette syndrome (TS). Therefore, the urinary concentrations of these TIQ derivatives were measured in patients with TS and patients with comorbid attention-deficit/hyperactivity disorder (TS + ADHD) compared with controls. Seventeen patients with TS, 12 with TS and ADHD, and 19 age-matched healthy controls with no medication took part in this study. Free levels of NSAL, NMNSAL, SAL, and NMSAL in urine were measured by a two-phase chromatographic approach. Furthermore, individual TIQ concentrations in TS patients were used in receiver-operating characteristics (ROC) curve analysis to examine the diagnostic value. NSAL concentrations were elevated significantly in TS [434.67 ± 55.4 nmol/l (standard error of mean = S.E.M.), two-way ANOVA, p < 0.0001] and TS + ADHD patients [605.18 ± 170.21 nmol/l (S.E.M.), two-way ANOVA, p < 0.0001] compared with controls [107.02 ± 33.18 nmol/l (S.E.M.), two-way ANOVA, p < 0.0001] and NSAL levels in TS + ADHD patients were elevated significantly in comparison with TS patients (two-way ANOVA, p = 0.017). NSAL demonstrated an AUC of 0.93 ± 0.046 (S.E.M) the highest diagnostic value of all metabolites for the diagnosis of TS. Our results suggest a dopaminergic hyperactivity underlying the pathophysiology of TS and ADHD. In addition, NSAL concentrations in urine may be a potential diagnostic biomarker of TS.
KW  - Tourette syndrome
KW  - ADHD
KW  - tics
KW  - biomarkers
KW  - tetrahydroisoquinoline derivates
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235771
SN  - 0300-9564
VL  - 128
ER  -