Using an approach that combines gene therapy with aromatic L-amino acid decarboxylase (AADC) gene and a pro-drug (L-dopa), dopamine, the neurotransmitter involved in Parkinson's disease, can be synthesized and regulated. Striatal neurons infected with the AADC gene by an adeno-associated viral vector can convert peripheral L-dopa to dopamine and may therefore provide a buffer for unmetabolized L-dopa. This approach to treating Parkinson's disease may reduce the need for L-dopa/carbidopa, thus providing a better clinical response with fewer side effects. In addition, the imbalance in dopamine production between the nigrostriatal and mesolimbic dopaminergic systems can be corrected by using AADC gene delivery to the striatum. We have also demonstrated that a fundamental obstacle in the gene therapy approach to the central nervous system, i.e., the ability to deliver viral vectors in sufficient quantities to the whole brain, can be overcome by using convection-enhanced delivery. Finally, this study demonstrates that positron emission tomography and the AADC tracer, 6-[ 18 F]fluoro-Lm-tyrosine, can be used to monitor gene therapy in vivo. Our therapeutic approach has the potential to restore dopamine production, even late in the disease process, at levels that can be maintained during continued nigrostriatal degeneration.

Nuclear magnetic resonance (NMR) imaging was employed to study 10 patients with Alzheimer's disease (AD) and seven healthy elderly control subjects. Coronal sections were used to make volumetric measurements of the hippocampus, ventricles, subarachnoid space, and brain parenchyma. The hippocampal volume (normalized relative to the size of the lenticular nucleus) was reduced by 40% in the AD group compared to the controls, with no overlap between the two groups. Overall measures of brain atrophy and ventricular and sulcal enlargement also showed significantly different group means, although with overlap between the two groups. Hippocampal atrophy did not correlate with either overall brain atrophy or dementia severity, although the degree of brain atrophy was correlated with dementia severity. These results show that NMR is capable of providing in vivo quantification of diminished hippocampal size in AD which is not correlated with overall brain atrophy and which may differentiate AD from normal aging.

No abstract