FUNCTIONAL RECOVERY IN PARKINSONIAN MONKEYS TREATED WITH GDNF

PARKINSON's disease results from the progressive degeneration of dopam ine neurons that innervate the striatum(1,2). In rodents, glial-cell-l ine-derived neurotrophic factor (GDNF) stimulates an increase in midbr ain dopamine levels, protects dopamine neurons from some neurotoxins, and maintains injured dopamine neurons(3-9). Here we extend the rodent studies to an animal closer to the human in brain organization and fu nction, by evaluating the effects of GDNF injected intracerebrally int o rhesus monkeys that have had the symptomatology and pathophysiologic al features of Parkinson's disease induced by the neurotoxin 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)(10-14). The recipients of G DNF displayed significant improvements in three of the cardinal sympto ms of parkinsonism: bradykinesia, rigidity and postural instability. G DNF administered every four weeks maintained functional recovery. On t he lesioned side of GDNF-treated animals, dopamine levels in the midbr ain and globus pallidus were twice as high, and nigral dopamine neuron s were, on average, 20% larger, with an increased fibre density. The r esults indicate that GDNF may be of benefit in the treatment of Parkin son's disease.