Pathophysiology and treatment of neurodegenerative disorders
The study of the human brain and its diseases is thrilling: it is the most complex structure in the body, from the molecular and cellular interactions that take place there to the interpretation of behaviour and emotions
The incidence of neurodegenerative diseases has increased considerably in recent years owing to the increase in life expectancy. These are diseases that not only cause suffering to patients and their families but also have a major social and economic impact. There is currently no treatment for halting neurodegenerative processes.Approach
The group studies the pathophysiologic mechanisms involved in different neurodegenerative diseases of the basal ganglia, which cause dysfunction and death of the neurons that control motor and/or cognitive functions. Using new and innovative technology, these studies make it possible to design new gene, cell and drug therapies.
The group is using a multidisciplinary and translational approach to develop new treatments to halt or slow neurodegenerative processes in diseases such as Huntington disease.
The group essentially uses two strategies to achieve this: neuroprotective therapies and neuro-regenerative therapies. The former are based on the study of the mechanisms that regulate neuronal plasticity, which maintain the connectivity of the neuron networks in different areas of the brain.
Neuro-regenerative therapies focus on the differentiation of embryonic stem cells, adult stem cells and IPS cells in neurons with the same profile as those affected in Huntington disease. It is thus possible to perform transplants that replace the dead neurons and recover motor function.
The group has determined several intracellular pathways involved in neuronal plasticity and the connectivity of the basal ganglia and the hippocampus, which are abnormal in mutated Huntington disease (BDNF/TrkB/p75, Cdk5, STEP, etc.).
This has allowed the group to identify new therapeutic targets and develop new treatments that it has tested in preclinical studies (in vivo and in vitro models). Some have already been used in international clinical trials.
Cell-therapy studies in Huntington disease have also advanced with the differentiation of human neurons with the structural and physiological characteristics of the neurons of the putamen/caudate nucleus, which can be transplanted to recover motor function.
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