A5053568588- Neurological disorders and treatments
- Parkinson's Disease Mechanisms and Treatments
- Pluripotent Stem Cells Research
- Nerve injury and regeneration
- Genetic Neurodegenerative Diseases
- Nuclear Receptors and Signaling
- CRISPR and Genetic Engineering
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neuropharmacology Research
- Biomedical Ethics and Regulation
- Mitochondrial Function and Pathology
- Neuroscience and Neural Engineering
- Neurogenetic and Muscular Disorders Research
- Virus-based gene therapy research
- Neurotransmitter Receptor Influence on Behavior
- Mesenchymal stem cell research
- Receptor Mechanisms and Signaling
- Botulinum Toxin and Related Neurological Disorders
- Spinal Dysraphism and Malformations
- RNA regulation and disease
- Biosensors and Analytical Detection
- Amyotrophic Lateral Sclerosis Research
- Congenital heart defects research
- Retinal Development and Disorders
- Autophagy in Disease and Therapy
Ikerbasque
2022-2025
BioCruces Health research Institute
2022-2025
Consejería de Salud y Consumo
2022-2023
Junta de Andalucía
2017-2023
Fundación Progreso y Salud
2020-2023
Sociedad Andaluza de Trasplantes de Órganos y Tejidos
2020-2021
Andalusian Agency for Healthcare Quality
2017-2018
Inspiralia
2017
Policlínica Gipuzkoa
2013
Navarrabiomed
2013
Although implantation of fetal dopamine (DA) neurons can reduce parkinsonism in patients, current methods are rudimentary, and a reliable donor cell source is lacking. We show that transplanting low doses undifferentiated mouse embryonic stem (ES) cells into the rat striatum results proliferation ES fully differentiated DA neurons. cell-derived caused gradual sustained behavioral restoration DA-mediated motor asymmetry. Behavioral recovery paralleled vivo positron emission tomography...
We report the first post-mortem analysis of two patients with Parkinson's disease who received fetal midbrain transplants as a cell suspension in striatum, and one case also substantia nigra. These had favourable clinical evolution positive 18F-fluorodopa PET scans did not develop motor complications. The surviving transplanted dopamine neurons were positively identified phenotypic markers normal control human nigra (n = 3), such tyrosine hydroxylase, G-protein-coupled inward rectifying...
Neural cells differentiated in vitro from human embryonic stem (hESC) exhibit broad cellular heterogeneity with respect to developmental stage and lineage specification. Here, we describe standard conditions for the use discovery of markers analysis cell selection hESC undergoing neuronal differentiation. To generate better-defined populations, established a working protocol sorting heterogeneous hESC-derived neural populations by fluorescence-activated (FACS). Using genetically labeled...
We used PET scans with the tracers [18F]fluorodeoxyglucose (FDG) and [11C]raclopride (RACLO) to study glucose metabolism dopamine D2 receptor binding in caudate nucleus putamen of 18 carriers Huntington's disease gene mutation (10 asymptomatic subjects eight untreated symptomatic patients an early stage). also performed MR1 measured bicaudate ratio (BCR) same subjects. Data were compared those from nine mutation-negative members families separate groups age matched controls. The repeated...
Dopamine, the major neurotransmitter depleted in Parkinson disease, can be synthesized and regulated vivo with a combination of intrastriatal AAV-hAADC gene therapy administration dopamine precursor l-Dopa. When tested MPTP-lesioned monkeys, this approach resulted long-term improvement clinical rating scores, significantly lowered l-Dopa requirements, reduction l-Dopa-induced side effects. Positron emission tomography [18F]FMT confirmed persistent AADC activity, demonstrating for first time...
Abstract It is currently not known whether dopamine (DA) neurons derived from human embryonic stem cells (hESCs) can survive in vivo and alleviate symptoms models of Parkinson disease (PD). Here, we report the use Noggin (a bone morphogenic protein antagonist) to induce neuroectodermal cell development increase yield DA hESCs. A combination stromal-derived inducing activity markedly enhanced generation neuroepithelial progenitors that could give rise neurons. In addition, diminished...
Several lines of evidence point to a significant role neuroinflammation in Parkinson's disease (PD) and other neurodegenerative disorders. In the present study we examined protective effect celecoxib, selective inhibitor inducible form cyclooxygenase (COX-2), on dopamine (DA) cell loss rat model PD. We used intrastriatal administration 6-hydroxydopamine (6-OHDA) that induces retrograde neuronal damage death, which progresses over weeks. Animals were randomized receive celecoxib (20...
The heterogeneity of protein-rich inclusions and its significance in neurodegeneration is poorly understood. Standard patient-derived iPSC models develop neither reproducibly nor a reasonable time frame. Here, we developed screenable "inclusionopathy" utilizing piggyBac or targeted transgenes to rapidly induce CNS cells that express aggregation-prone proteins at brain-like levels. Inclusions their effects on cell survival were trackable single-inclusion resolution. Exemplar cortical neuron...
Adeno-associated virus type2 (AAV-2) binds to heparan-sulfate proteoglycans on the cell surface. In vivo, attachment of viral particles cells adjacent injection tract limits distribution AAV-2 when infused into CNS parenchyma and heparin co-infusion might decrease binding in vicinity infusion tract. We have previously shown that combined with convection enhanced delivery enhances GDNF family trophic factors (heparin-binding proteins) rat brain. this work we show significantly increases...
Dopamine (DA) neurons can be derived from human and primate embryonic stem (ES) cells in vitro. An ES cell–based replacement therapy for patients with Parkinson's disease requires that vitro–generated maintain their phenotype vivo. Other critical issues relate to proliferative capacity risk of tumor formation, the capability migration integration adult mammalian brain. Neural induction was achieved by coculture parthenogenetic (Cyno‐1) stromal cells, followed sequential exposure midbrain...
Blindness due to corneal diseases is a common pathology affecting up 23 million individuals worldwide. The tissue-engineered anterior human cornea, which currently being tested in Phase I/II clinical trial treat severe trophic ulcers with preliminary good feasibility and safety results. This bioartificial cornea based on nanostructured fibrin-agarose biomaterial containing allogeneic stromal keratocytes epithelial cells, mimicking the native terms of optical, mechanical, biological behavior....
Animal models play a pivotal role in translational neuroscience but recurrent problems data collection, analyses, and interpretation, lack of biomarkers, tendency to over-reliance on mice have marred progress, leading one the highest attrition rates drug translation. Global initiatives improve reproducibility model selection are being implemented. Notwithstanding, still preferred animal species human brain disorders even when translation has been shown be limited. Non-human primates better...
Abstract The use of in vitro expanded human CNS precursors has the potential to overcome some ethical, logistic and technical problems fetal tissue transplantation Parkinson disease. Cultured rat mesencephalic proliferate response bFGF upon mitogen withdrawal, differentiate into functional dopamine neurons that alleviate motor symptoms Parkinsonian rats (Studer et al. [ 1998 ] Nat. Neurosci. 1:290–295). successful clinical application precursor technology disease will depend on efficient...
Recent studies have shown that progressive supranuclear palsy (PSP) could be inherited, but the pattern of inheritance and spectrum clinical findings in relatives are unknown. We here report 12 pedigrees, confirmed by pathology four probands, with familial PSP. Pathological diagnosis was according to recently reported internationally agreed criteria. The phenotypes these families variable including 34 typical cases PSP (12 probands plus 22 secondary cases), three patients postural tremor,...
<b><i>Objective:</i></b> To study the clinical significance of metabolic alterations as measured in vivo with proton MRS striatum patients Huntington's disease (HD). <b><i>Methods:</i></b> Localized, single-voxel was performed on basal ganglia 10 HD (4 presymptomatic gene carriers and 6 akinetic patients) 5 age-matched healthy individuals. Metabolite quantification by referring areas respective spectral peaks to that water analyzed voxel. The spectroscopic findings were correlated motor...
The identity and functional potential of dopamine neurons derived in vitro from embryonic stem cells are critical for the development a cell-based replacement therapy Parkinson's disease. Using parthenogenetic primate cell line, we have generated that display persistent expression midbrain regional cell-specific transcription factors, which establish their proper allow survival. We show here transplantation restores motor function hemi-parkinsonian, 6-hydroxy-dopamine-lesioned rats. Exposure...
Mutations in leucine-rich repeat kinase 2 (LRRK2) contribute to both familial and idiopathic forms of Parkinson's disease (PD). Neuroinflammation is a key event neurodegeneration aging, there mounting evidence LRRK2 involvement inflammatory pathways. In previous study, we described an alteration the response dermal fibroblasts from PD patients expressing G2019S R1441G mutations LRRK2. Taking advantage cellular reprogramming, generated induced pluripotent stem cell (iPSC) lines neurons...
In animal models of Parkinson's disease, gene transfer aromatic L-amino acid decarboxylase (AADC) leads to an increase in the capacity striatum decarboxylate exogenous L-DOPA. However, functional effects enhanced L-DOPA dopamine conversion have not been explored. Here, we show that following adeno-associated virus (AAV)-AADC transduction, transgenic AADC is able more efficiently so a dose ineffective before elicits motor asymmetry (rotational behavior) transfer. Furthermore, rotation scores...
Dopamine (DA) receptors play a central role in such diverse pathologies as Parkinson's disease, schizophrenia, and drug abuse. We used an amphetamine challenge combined with pharmacologic magnetic resonance imaging (phMRI) to map DA-associated circuitry nonhuman primates high sensitivity spatial resolution. Seven control cynomolgous monkeys 10 MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated parkinsonian were studied longitudinally using both positron emission tomography (PET)...
Background: Huntington's disease (HD) is generally considered a hyperkinetic disorder, although hypokinetic features are part of the motor syndrome. Moreover, striatum to play key role in initiating and executing programs achieving optimal scheduling response generation. Controversial results regarding association between clinical markers progression might be result inadequate restriction signs choreatic