Progress and Prospects in Parkinson's Research/Therapy/Symptomatic Relief/Bradykinesia

Background
Bradykinesia - literally 'slow movement' is one of the signature symptoms of Parkinson's Disease. It manifests itself as a movement disorder with a shuffling gait, asymetric stride length, a stooped posture, a failure to swing one arm when walking and an inclination to overbalance. Patients sometimes report that it feels as though one foot is stuck to the floor. Sometimes it can be overcome by cognitive action such as walking to a marching beat or visual cueing where the slow leg kicks an imaginary football or is aimed at regularly spaced cracks in the footway. Walking is to a large extent an autonomic function and is susceptible to dopamine deficiency.

Arvid Carlsson
The person most closely associated with the discovery of Levodopa is Arvid Carlsson. While working as a professor at the University of Lund, Sweden in the 1950s he found a method of measuring the amount of dopamine in brain tissue and demonstrated its function as a neurotransmitter key to effecting movement in animals. He unravelled the metabolic sequence leading to the formation of dopamine in the basal ganglia and connected Parkinsonian movement disorders to dopamine deficiency. For this work he was awarded the Nobel Prize for Chemistry in Physiology or Medicine in 2000.

Dopamine is a relatively simple compound to manufacture artificially but the size and shape of the molecule is such that it will not pass through the blood brain barrier and is therefore ineffective if taken orally. However Levodopa (L-Dopa) is a precursor in the metabolic sequence leading to the formation of dopamine and it has therefore become the most commonly prescribed drug  for the treatment of Parkinson’s Disease.

1996

Morris et al. carried out a detailed evaluation of walking patterns in PD patients and tested a number of corrective strategies. They concluded:-

" The ability to generate a normal stepping pattern is not lost in Parkinson’s Disease and gait hypokinesia reflects a difficulty in activating the motor control system. Normal stride length can be elicited during Parkinson’s Disease using attentional strategies and visual cues. Both strategies appear to share the same mechanism of focussing attention on the stride length.  The effect of the attention appears to require constant vigilance to prevent reverting to more automatic control mechanisms. "

2012

Mak measured and compared the walking patterns of PD patients and controls using a treadmill. The conclusion was:- "As reduced step length persisted when the control subjects walked at a speed similar to that of patients, our finding suggests that PD patients had a fundamental problem in regulating the amplitude of step length during walking."