Now I've never performed histopathology on human nigral or locus ceruleus tissue, but when one looks for causes of PD, one gets something like this.

"Dopamine is a neurotransmitter that stimulates motor neurons (nerve cells), and is necessary for organized, coordinated movement and maintenance of normal muscle tone. Parkinson's is caused by degeneration of nerve cells in the substantia nigra ("black substance") and the locus ceruleus ("blue location") where dopamine is produced and stored. Loss of dopamine causes neurons (cells in the brain) to fire out of control, leaving people unable to direct or control movement normally."

But Daffy says that the cells themselves are not lost, just their ability to produce, store and release dopamine is compromised. It could be a biosynthesis problem (and just as an aside Keith, I was looking today and found that 3-hydroxy phenylalanine, can be 4-hydroxylated to give dopa, which infers yet another enzyme catalysed process, as I wouldn't expect phenylalanine 3-hydroxylase to be the same entity as tyrosine hydroxylase, you know how specific enzymes are). It could be intracellular damage caused by either an endogenous (gene expression) or exogenous (toxic agent). If it's gene expression it could be something turned on by some mistake which could be initiated by lack of cofactors or rampant free-radical oxidative damage to certain organelles, that result in either the stopping of some part of the dopamine cycle due to cell damage, or outright "kicking in of apoptosis to completely kill the cell instead of just leaving it in a damaged, weakened, reversable (or not), non-dopamine producing cell. I don't know becuase i've never seen a "dead" substantia nigra, but only go by what ive read, that is, that the cells are actually dead.
All this is pertinent here because the stated "gene therpapy" work was done on the wrong cells to affect any reversal of PD. If what you say is true (that most nigral cells are not dead, but just in an inoperative (as far as dopamine production and transmission goes) state, then they should try transfecting enzymatic constructs into nigral or LC neurons?
Of course they would have to know exactly what the "problem" is whether it's a dearth of a critical dopamine producing enzyme, or whether it's primarily a "cell damaging" factor, one which prevents the cell from acting as a dopaminergic neuron. So maybe, most of what the causal process leading to PD could be DNA damage, since DNA is the ultimate blueprint for production of RNA which holds the enzymatic code necessary to actually go out of the cell nucleus and assemble the chains of amino acids that constitute an "enzyme".
It's all so complicated to us, but to a trained biochemist, with all their expensive tools, wouldn't you think that they would have figured some "truths" about all this by now? cs