A Case of L-Dopa-Responsive Parkinsonian Syndrome After Low-Dose Oral Methotrexate Intake

Papapetropoulos, Spiridon; Liossis, Stamatis–Nick C.; Daousis, Dimitrios; Katsoulas, Georgios; Apostolopoulos, Dimitrios; Chroni, Elisabeth

doi:10.1097/00002826-200403000-00011

Cited by 3 publications

(3 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CYP2W1 is expressed in a cancer-specific way and converts pro-dugs as well as fatty acids like arachidonic acid ( Pan and Ong, 2017 ). CYP20A1 is highly expressed in the brain, especially in the Substantia nigra ( Stark et al, 2008 ; Lemaire et al, 2016 ) , and a connection to methotrexate toxicity has been found ( Papapetropoulos et al, 2004 ; Aslibekyan et al, 2014 ) although this finding is controversial ( Koponen et al, 2022 ). Interestingly, for CYPs of the CYP4 family (CYP4A22, CYP4X1 and CYP4Z1) a participation in fatty acid conversion and epoxide formation of eicosatrienoic acids has been described ( Zöllner et al, 2009 ; Carver et al, 2014 ; McDonald et al, 2017 ; Durairaj et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

A CYPome-wide study reveals new potential players in the pathogenesis of Parkinson’s disease

Hartz

Fehlmann²,

Wagenpfeil³

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

Genetic and environmental factors lead to the manifestation of Parkinson’s disease (PD) but related mechanisms are only rudimentarily understood. Cytochromes P450 (P450s) are involved in the biotransformation of toxic compounds and in many physiological processes and thus predestinated to be involved in PD. However, so far only SNPs (single nucleotide polymorphisms) in CYP2D6 and CYP2E1 have been associated with the susceptibility of PD. Our aim was to evaluate the role of all 57 human P450s and their redox partners for the etiology and pathophysiology of PD and to identify novel potential players which may lead to the identification of new biomarkers and to a causative treatment of PD. The PPMI (Parkinson’s Progression Markers Initiative) database was used to extract the gene sequences of all 57 P450s and their three redox partners to analyze the association of SNPs with the occurrence of PD. Applying statistical analyses of the data, corresponding odds ratios (OR) and confidence intervals (CI) were calculated. We identified SNPs significantly over-represented in patients with a genetic predisposition for PD (GPD patients) or in idiopathic PD (IPD patients) compared to HC (healthy controls). Xenobiotic-metabolizing P450s show a significant accumulation of SNPs in PD patients compared with HC supporting the role of toxic compounds in the pathogenesis of PD. Moreover, SNPs with high OR values (>5) in P450s catalyzing the degradation of cholesterol (CYP46A1, CY7B1, CYP39A1) indicate a prominent role of cholesterol metabolism in the brain for PD risk. Finally, P450s participating in the metabolism of eicosanoids show a strong over-representation of SNPs in PD patients underlining the effect of inflammation on the pathogenesis of PD. Also, the redox partners of P450 show SNPs with OR > 5 in PD patients. Taken together, we demonstrate that SNPs in 26 out of 57 P450s are at least 5-fold over-represented in PD patients suggesting these P450s as new potential players in the pathogenesis of PD. For the first time exceptionally high OR values (up to 12.9) were found. This will lead to deeper insight into the origin and development of PD and may be applied to develop novel strategies for a causative treatment of this disease.

show abstract

Section: Resultsmentioning

confidence: 99%

A CYPome-wide study reveals new potential players in the pathogenesis of Parkinson’s disease

Hartz

Fehlmann²,

Wagenpfeil³

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…While our patient has been exposed to methotrexate, it is unlikely to have played a role in the development of his parkinsonism. Indeed, there are only 2 reported cases of methotrexate induced parkinsonism in the literature [ 11 , 12 ]. The first was a cancer patient who received high doses of the drug combined with brain radiation therapy and leucoencephalopathy [ 11 ], and the second was a rheumatoid arthritis patient who developed a transient dopamine responsive parkinsonsim, but with normal [123I]-B-CIT SPECT excluding neurodegenerative PD [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, there are only 2 reported cases of methotrexate induced parkinsonism in the literature [ 11 , 12 ]. The first was a cancer patient who received high doses of the drug combined with brain radiation therapy and leucoencephalopathy [ 11 ], and the second was a rheumatoid arthritis patient who developed a transient dopamine responsive parkinsonsim, but with normal [123I]-B-CIT SPECT excluding neurodegenerative PD [ 12 ]. In theory, methotrexate could uncover an underlying idiopathic Parkinson's disease in our patient with young onset PD, but this was never reported before and could not be confirmed.…”

Section: Discussionmentioning

confidence: 99%