What is Parkinson's Disease ?

Parkinson

James Parkinson

1755-1824

Parkinson’s disease (PD) is a chronic neurodegenerative disease affecting approximately 1% of people over 65 years of age, and as such is likely to become more common as the population ages and lives longer.  It is characterised clinically by the development of a disorder of movement and pathology within a series of structures collectively termed the basal ganglia. Symptoms of PD have been known and treated since medieval times. However, it was not formally recognized and the symptoms were not documented until 1817 in "An Essay on the Shaking Palsy" by the British physician James Parkinson, and the name given to the condition by Charcot some 50 odd years later. The disease is characterised by the development of pathology (alpha-synuclein positive lewy bodies) in selective groups of brain nerve cells, and with time, this critically involves the dopaminergic neurons of the substantia nigra (nerve cells that project to the striatum and release dopamine there). The loss of these dopaminergic cells causes problems of motor control including; tremor, or trembling in hands, arms, legs, jaw, and face; rigidity, or stiffness of the limbs and trunk; bradykinesia, or slowness of movement; and postural instability. However the disease probably begins with pathology outside the substantia nigra and a constellation of features such as disturbances of sleep, mood and olfaction. Indeed, there is now a growing recognition that PD has as many non-motor as motor features. Nevertheless the disease is currently defined clinically by its classical motor features, which in the early stages can be effectively treated with dopaminergic drugs. But as the disease progresses, the motor features become harder to treat and do not respond as well  to dopamine drug therapies , which actually start to cause their own side effects such as involuntary movements (L-dopa induced dyskinesias – LIDs) . In addition, some of the other non-motor features of the disease become more prominent including cognitive difficulties and dementia

 

The disease

At present, there is no cure for PD, but as already stated dopaminergic medications can provide relief from the symptoms. The commonly applied therapies include the use of Levodopa and Dopamine receptor agonists (Apomorphine, Pramipexole, Ropinirole, Rotigotine), inhibitors of Monoamine Oxidase B MAOB (Selegiline, Rasagiline), inhibitors of Catechol O-methyl Transferase (Entacapone, Tolcapone) or Anticholinergics (Benzatropine). In addition, other drugs can be used for other aspects of the disease such as amantadine for L.dopa induced involuntary movements (dyskinesias). In addition there has been recent interest in the use of deep brain stimulation to alleviate some aspects of the disease, and this has been shown to be especially successful when the stimulation is done at high frequency in the subthalamic nucleus bilaterally. However none of these therapies are reparative, and approaches using this principle have been tried in PD including growth factor infusion and dopaminergic cell transplants.

The TRANSEURO consortium has been established with the aim to develop a better cell therapy approach for PD patients using fetal dopaminergic cells.  TRANSEURO partners will join forces in a new round of experimental work as well as clinical trials. In the first instance, fetal tissue containing the developing dopaminergic neuroblasts from the midbrain of human fetuses will be used, with the expectation for subsequent larger scale trials if these initial open label studies prove successful.

 

 

 

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