[caldeerster]

A potential gene therapy for Parkinson's disease can correct motor deficits in monkeys without causing the jerky, involuntary movements that often accompany long-term treatments for the disease. The approach is undergoing preliminary testing in a handful of human patients, who have all shown promising signs of improvement.

At present, the most common remedy for Parkinson's disease involves replacing dopamine — the neurotransmitter that is depleted in patients with the disease — by administering the dopamine precursor levodopa, or L-DOPA. Most patients initially regain near-normal motor control, but after several years on L-DOPA the majority become saddled with debilitating physical and psychological side effects. To remedy the situation, Stéphane Palfi, a neurosurgeon at the French Atomic Energy Commission's Institute of Biomedical Imaging in Orsay, and his colleagues turned to gene therapy. First, they gave macaque monkeys a harsh neurotoxin that caused the animals to develop bodily tremors, unstable posture and severe joint rigidity — hallmarks of advanced Parkinson's disease. The researchers then injected the monkeys' brains with three genes essential for synthesizing dopamine.

They saw significant improvements in motor behaviour after just two weeks, without any visible adverse effects. "We don't see any problems in these monkeys," says Palfi. One animal even exhibited sustained recovery more than 3.5 years later. Notably, the monkeys did not display the jerky, uncontrolled movements that occur in most patients and monkeys after prolonged oral L-DOPA treatment.

This success in monkeys paves the way for future studies in humans, says Palfi, who reported his animal results today in the journal Science Translational Medicine1. "This is the exact situation that we will face in the clinic," he says. Palfi's team has already tested two different doses of the three-gene-containing virus in six human patients, and is now investigating an intermediate dose that matches that used in the monkeys, with corrections for brain size. Once the researchers find the optimal dose, they plan to move the experimental treatment into Phase II trials, Palfi says.

http://www.nature.com/news/2009/0910...2009.1001.html

[girija]

Thanks. This seems promising, still a long way to go though...
girija

[lurkingforacure]

I have been following this company for some time and wonder how taking brain cell A (one which doesn't make dopamine) and turning it into brain cell B (one which does) will affect the body long term. What function did brain cell A have to begin with, and what happens when that function no longer occurs with the same number of cells? Will there be a deficit in some other way? This is kind of like robbing Peter to pay Paul. I have read nothing about this concern and personally wonder whether we can really safely substitute cellular function in this way.

I'm open-minded, just not sure about the long-term effects of this particular therapy.

And why, in the name of everything holy, are so many companies continuing to R&D therapies that require brain surgery of some sort? Ceregene, brain surgery, spheramine, brain surgery, now prosavin, again, brain surgery. Did we learn nothing from Amgen, where it seems like the real reason it was stopped was commercial viability-because you just can't perform brain surgery on millions of PD sufferers? Ugh. I have no problem with brain surgery for adult stem cells (trial going on now, if I'm not mistaken), there's no other way to get the new cells physically where they need to be, but these other therapies, geez. Maybe I'm just showing my ignorance, but it seems to me that these companies are assuming an awful lot of folk can afford/have insurance to pay for all these brain surgeries that will be necessary to get their product, assuming it even works.

[JoeM]

Originally Posted by lurkingforacure

What function did brain cell A have to begin with, and what happens when that function no longer occurs with the same number of cells? Will there be a deficit in some other way?

If I have correctly understood, you don't replace the original cell function, but add to that cell the capacity to manufacture dopamine.

My fear is different: dopamine producing cells are the first to fall because they are especially sensitive to other changes in the brain (iron, Ca, alpha-synuclein...), if you turn other cells into dopamine producing cells, wouldn't those cells become affected in the long term by the same alterations that kill our SNpc cells in the first place?