Parkinson´s disease (PD) is one of the most serious neurological diseases with more patients than multiple sclerosis, amyotrophic lateral sclerosis, muscular dystrophy and myasthenia gravis combined. PD is a chronic, progressive neurodegenerative disorder characterized by hypokinesia, tremor and muscular rigidity.
Parkinson’s Disease is growing rapidly
PD is generally age-specific affecting approximately 1% of the population over the age of 60, 1.6% of those over the age of 65 and 3% of those over 75. PD is growing rapidly with a growing population and an increasing share of elderly in the population.
The age of debut is usually between 55 and 60 years. The disease is characterized by rigidity, tremor and bradykinesia (poverty of motion) caused by a massive loss of nigrostriatal neurons and subsequently a lack of dopamine. Later, during the course of the disease, cognitive and behavioural problems may arise. The symptoms of Parkinson’s disease appear upon a loss of approximately 80% of dopamine neurons.
Nobel laureate Arvid Carlsson discovered in the late 1950s that the natural amino acid levodopa (L-dopa) is converted to dopamine when it reaches the brain. Levodopa is still – ever since – ”the golden standard” for the treatment of PD. Levodopa treatment of patients suffering from PD improves the patient’s ability to function in the society and their quality of life and reduces both individual and societal costs. Levodopa is the precursor to the neurotransmitters dopamine, norepinephrine and epinephrine. In spite of the massive loss of dopamine neurons in early stages of the disease, an adequate storage capacity is still maintained enabling an even release of dopamine into the synaptic cleft at oral intake of levodopa tablets.
Unfortunately, pharmacokinetic and pharmacodynamic problems (on-off symptoms) develop after several years of oral treatment with levodopa. The on-off symptoms arise after approximately five years of oral treatment in the form of motor fluctuations – ranging from disabling dyskinesia (involuntary movements) to akinesia (total lack of mobility). On-off symptoms worsen during the course of the disease.
Arvid Carlsson, Professor Emeritus and Nobel laureates tells the DOPA story.
A new view
Researchers believe that on-off symptoms most likely are caused by the way in which levodopa is administered. More specifically, it is believed that the intermittent administration of levodopa through oral treatment, together with the degeneration of dopaminergic neurons, are the main causes of the development of on-off symptoms. Intermittent oral treatment eventually leads to a narrower therapeutic window for levodopa making oral administration even more problematic. It is a shared view that a more continuous administration of levodopa would be beneficial to the PD patients.
Accordingly, a therapeutic strategy that could deliver levodopa to the brain in a more continuous and physiologic manner might be expected to provide all of the benefits of standard levodopa but with reduced motor complications. Such a levodopa formulation might replace a majority of the current dopaminergic antiparkinsonian medications and this without any need for surgery.