Use of Cuban recombinant human erythropoietin in Parkinson's disease treatment.

INTRODUCTION: Recombinant human erythropoietin is used primarily to treat anemia. There is evidence of its neuroprotective capacity from preclinical studies in Parkinson's disease and other neurodegenerative diseases. Recombinant human erythropoietin produced in Cuba (ior-EPOCIM) is registered and approved for use in humans in Cuba and in a number of other countries. OBJECTIVE: Assess safety and possible neuroprotective effect of ior-EPOCIM in a group of Parkinson's disease patients. METHODS: A three-phase exploratory study (proof of concept) was conducted from August 2008 to April 2009: preliminary assessment, treatment (weeks 1-5), and post-treatment (weeks 6-35). Participants were 10 Parkinson's disease patients (8 men, 2 women) from the outpatient clinic at the International Neurological Restoration Center, all at least one year post onset, aged 47-65 years. The ior-EPOCIM was administered subcutaneously in a once-weekly dose (60 IU/kg body weight) for five weeks. Therapy with patients' antiparkinsonian drugs was maintained throughout the study, except during motor examination, conducted following a 12-hour withdrawal (OFF condition). Safety was evaluated primarily by recording adverse events (by intensity and causality) from start of treatment until the study's completion. Hematological parameters and blood pressure were also measured because of their direct relationship to the medication's action. To evaluate possible neuroprotective activity, variables were included related to patients' motor function and cognitive and affective status, measured using internationally recognized scales. All variables were evaluated before, during and after treatment. Data were processed using a fixed-effects linear model, with a repeated-measures design (significance level p ≤ 0.05). RESULTS: Three patients experienced mild adverse events (precordial discomfort and hypertension in one; leg fatigue in another; renal colic in a third), with a possible causal relationship in the first two that was neither life threatening nor required hospitalization. Hemoglobin was the only hematological parameter that showed a growing and significant increase (p < 0.001), but without reaching pathological levels. The other variables presented clinically positive and statistically significant changes compared to pretreatment assessment: motor function (p < 0.001), cognitive status (p < 0.001) and mood (p = 0.013). CONCLUSIONS At the dosage used, ior-EPOCIM was safe and well tolerated in these Parkinson's disease patients. Further studies are needed to corroborate these results and evaluate the medication's possible neuroprotective effect. KEYWORDS Parkinson disease, erythropoietin, recombinant proteins, neuroprotective agents, clinical trial, safety, ior-EPOCIM, Cuba.

A theoretical formulation of the electrophysiological inverse problem on the sphere.

The construction of three-dimensional images of the primary current density (PCD) produced by neuronal activity is a problem of great current interest in the neuroimaging community, though being initially formulated in the 1970s. There exist even now enthusiastic debates about the authenticity of most of the inverse solutions proposed in the literature, in which low resolution electrical tomography (LORETA) is a focus of attention. However, in our opinion, the capabilities and limitations of the electro and magneto encephalographic techniques to determine PCD configurations have not been extensively explored from a theoretical framework, even for simple volume conductor models of the head. In this paper, the electrophysiological inverse problem for the spherical head model is cast in terms of reproducing kernel Hilbert spaces (RKHS) formalism, which allows us to identify the null spaces of the implicated linear integral operators and also to define their representers. The PCD are described in terms of a continuous basis for the RKHS, which explicitly separates the harmonic and non-harmonic components. The RKHS concept permits us to bring LORETA into the scope of the general smoothing splines theory. A particular way of calculating the general smoothing splines is illustrated, avoiding a brute force discretization prematurely. The Bayes information criterion is used to handle dissimilarities in the signal/noise ratios and physical dimensions of the measurement modalities, which could affect the estimation of the amount of smoothness required for that class of inverse solution to be well specified. In order to validate the proposed method, we have estimated the 3D spherical smoothing splines from two data sets: electric potentials obtained from a skull phantom and magnetic fields recorded from subjects performing an experiment of human faces recognition.