Parkinson's disease, Huntington's disease and other neurodegenerative movement disorders

Introduction

This program brings together 26 basic and clinical research groups with a fundamentally translational nature that join forces in the study of neurodegenerative diseases of diverse etiology, but which present significant problems in patient mobility. Parkinson's disease, Huntington's chorea and different types of ataxias, among other movement disorders, are included in this group of diseases, in order of prevalence.

Lines of Research

Line 1: Parkinson's disease

Parkinson's disease (PD) is mainly characterized by neuronal loss and the formation of Lewy bodies and neurites in the substantia nigra and the consequent loss of striatal dopamine (DA). However, it is currently well known that PD is a multisystem neurodegenerative process, in which, as the neurodegenerative process evolves, numerous regions of the nervous system are affected and there is a deficit in various neurotransmission and neuromodulation systems. It is estimated that PD affects some 160,000 people in Spain, a figure that is expected to increase as a result of the progressive aging of the population.

Although preventing and correcting DA deficiency remain important goals, they cannot be considered the greatest challenge in PD today. Within this area it is considered of fundamental importance to progress in the definition of:

1. Key aspects related to the etiopathogenesis of PD,
2. pathophysiological mechanisms related to disease onset and progression,
3. the development of symptomatic treatments and, above all, neuroprotective or curative treatments.

In this way, the aim is to achieve true translational research, whose main objectives are the disease and the patient. The most relevant research topics in this line are:

• Cognitive impairment and non-motor problems of PD.
• Biomarkers of Parkinson's disease.
• Problems related to symptomatic treatment: Dyskinesias.
• New targets and novel therapeutic strategies in Parkinson's disease.
• Circuits and pathophysiology of the basal ganglia.
• Neuronal stress, cell protection and death in Parkinson's disease.
• Neurogenesis and cell therapy in Parkinson's disease.
• Early biomarkers in Parkinson's disease.

Line 2: Huntington's disease and ataxias

This program also focuses on research into other neurodegenerative diseases, such as Huntington's disease (HD) and ataxias. HD is characterized by the initial loss of spiny interneurons of the striatum. It is an autosomal dominant neurodegenerative pathology with complete penetrance caused by polyglutamine expansion in the N-terminus of huntingtin. HD has no treatment and leads to death in between 10 and 20 years depending on the number of polyglutamines, the age of onset, some unknown environmental factors and the modulation of some genes, some of which have been located, but remain unidentified. HD has a much lower prevalence than AD or PD, 10 cases/100,000 inhabitants, and it is estimated that there are around 4,000 patients in Spain and around 50,000 in the European Union. The social and health cost involved is great, both due to the importance of motor and cognitive deficits, as well as the severity of the problems of behavioral alterations that patients present.

There are a large number of attempts at neuroprotection with drugs that modify the supposed pathogenic mechanisms or that are used in other neurodegenerative diseases. These drugs include inhibitors of neuronal excitation, respiratory chain coenzymes, vitamins, antioxidants, co-adjuvants in energy production, etc. Some of these products offer promising results in experimental models of the disease but, unfortunately, these have not been confirmed in the clinic.

HD research is important because it is the best studied and most prevalent model of neurodegenerative diseases caused by triplet expansions, which also includes some. Discovering the pathogenic mechanisms of HD and finding an effective treatment, from a neuroprotective or eradicative point of view, would have immediate implications for any of the neurodegenerative diseases caused by triplet expansions.

The main research topics in this line are:

• Identification of the molecular and cellular bases of Huntington's disease.
• Experimental studies in animal models of Huntington's disease.
• Clinical, genetics and neuropathology of Huntington's disease.

Research Groups