Anales de la RANM

57 A N A L E S R A N M R E V I S T A F U N D A D A E N 1 8 7 9 SERUM MYELOPEROXIDASE AND PARKINSON´S DISEASE Fernández-Espejo E An RANM. 2022;139(01): 56 - 66 The enzyme myeloperoxidase (MPO) has been implicated in the development of Parkinson´s disease (PD) (1-5). Thus, MPO is expressed by neurons in the substantia nigra pars compacta , and this enzyme contributes to α-synuclein pathology (6, 7). Studies on MPO cell expression in PD have yielded conflicting results. Some authors have reported increased MPO expression in surviving neurons and active glial cells in the substantia nigra in diseased patients and animal models of PD (7-9). Other authors have described that the number of MPO-immunoreactive blood-derived cells, rather than microglia, is increase in basal ganglia of human PD brains (10). MPO represents an essential component of the immune defense system and is expressed by periph- eral phagocytes (neutrophils and monocytes/ macrophages) and brain glial cells (microglia and astrocytes) (3-5, 11). The main biochemical function of MPO is to catalyze the reaction between hydrogen peroxide and chloride giving rise to hypochlorite, chlorinated products, and other reactive species, all powerful microbicidal molecules (5, 12-14). It is worth noting that inflammation and oxidative stress are implicated in PD pathogenesis (15-17), and MPO-derived products are pro-inflammatory and pro-oxidant compounds which can damage neurons (2-6, 18-20). The cytotoxicity of MPO and its localization in brain cells indicate its clinical importance, and this enzyme has been proposed to be a target for antiparkinsonian treatment (10, 22, 23). Recently, Jucaite et al (23) have provided support for proof of mechanisms of AZD3241, selective inhibitor of MPO, in PD patients, though the authors recognize that longer treatment is required to know if the effects are beneficial for therapy. To date, no study has examined how MPO in human biofluids relates to motor features in idiopathic PD. The hypothesis is that myeloperoxidase in blood serum or the cerebro- spinal fluid (CSF) might be involved in dopami- nergic cell loss in PD. The objective was hence to look at the relationship of MPO concentration in serum and the CSF with demographic, clinical and tomographic variables of the disease. The extent and degree of nigrostriatal dopaminergic cell loss was evaluated by using single-photon emission computed tomography (SPECT). 2.1. Participants This is a prospective, observational, and case-control study, where thirty-six patients with idiopathic PD and 30 controls were enrolled at Hospitals Macarena and Valme, Sevilla, Spain, from 2012 to 2017. Patients were diagnosed of PD if they present all three classic motor signs of parkinsonism (bradykinesia, rigidity, and resting tremor), and a reliable loss of dopaminergic signal on basal ganglia, as measured with 123 I-Ioflupane DAT-SPECT (24-26). To exclude hereditary forms of Parkinsonism, those patients with family members with PD, younger than 45 years old, or with atypical deficits, were discarded. Patients at advanced stages of PD (Hoehn-Yahr stages 4 and 5) were not included in the study. Control subjects, free of neurological disorder, were recruited from volunteers or patients´ relatives. They were group-matched by age and gender to PD subjects. Controls were excluded if they had a first-degree family member with a neurological disorder. Informed consent forms were obtained from all the subjects. All protocols were approved by the internal ethics and scientific boards of Junta de Andalucia (PEIBA, CEI-Sevilla-Sur #5/10/2015 & #2017-121418738), Hospital Valme (CEI-Valme, #10/05/2018 & #1694-M1-19), Hospital Macarena (CEI-Macarena, 19/05/2010 & 29/10/2013), and Universidad de Sevilla (CEI-27/05/2010). The subjects' consent was obtained according to the Declaration of Helsinki (BMJ 1991; 302:1194). 2.2. Demographic and clinical information A standardized study was carried out, including information such as age, gender, hypertension, diabetes, rating scales of disease severity, and pharmacological treatment. Hypertension was diagnosed when blood pressure repeatedly (two measures fifteen days apart) exceeded 140 mmHg (systolic) and/or 90 mmHg (diastolic) or when a subject was taking antihypertensive medica- tion. Diabetes was diagnosed according to WHO criteria (fasting plasma glucose ≥ 126mg/dl or 2–h plasma glucose ≥ 200mg/dl). Rating scales were 1.INTRODUC TION 2. MATERIAL AND METHODS tales, y dicha reducción fue mayor en putamen que en núcleo caudado (p<0.0001). La reducción porcentual de la señal dopaminérgica en estriado y putamen se correlacionó con las escalas de gravedad motora. Conclusiones. Se demuestra que la mieloperoxidasa sérica está elevada en la EP y se relaciona con la gravedad motora y la reducción de señal dopaminérgica estriatal. Los resultados permiten proponer que cuantificar los niveles de MPO en suero podría ser útil para el diagnóstico de la EP, y que la inhibición de dicha enzima podría ser un arma terapéutica. El estudio confirma que el putamen presenta mayor pérdida de señal dopaminérgica que el núcleo caudado, y las escalas de gravedad motora reflejan adecuadamente la pérdida dopaminérgica nigroestriatal.