"It's almost like an overdose," he adds, "even though dopamine levels don't reach supernormal levels, but still the balance is artificially asymmetric."

PET PREDICTIONS


And identifying good candidates for the procedure was something PET was good at, according to Dr. Eidelberg.

Patients whose FDOPA scans indicated they had relatively stronger dopamine activity (but not so much as to provoke a GID reaction) in the putamen were vastly more likely to improve after the operation.

"You didn't have to do the graft and wait," says Dr. Eidelberg. "We were able to identify based on amount of dopamine they lost."

And it did all this because FDOPA proved to be an excellent biomarker of the disease, he says. Uptake of the radiotracer shot up to 55 percent of normal signal ratio after transplantation, with higher levels of uptake associated with better outcomes.

"[This] lends credence to clinical assessment and gives objective measure to gauge improvements," Dr. Eidelberg notes.

AGE CLARIFICATIONS

The study, which followed 33 of the original 39 subjects for two years after surgery, and 15 after four years, also cleared up an outstanding mystery from the original work: why patients under 60 seemed to benefit most from transplant. The reason is, they didn't.

Age differences, which showed up in the original study that followed subjects only one year after the operation, disappeared after the two-year mark. Dr. Eidelberg thinks it just takes aging brains longer to form the necessary connections with the graft.

"The [nerve] signaling has to move across multiple synaptic contacts till it hits the motor region," he says. "When you're older, the grafts don't readily form these synaptic connections. It's not that they don't do it, it just takes longer."

The earlier study also found a sex difference, with men, but not women, showing significant improvements after transplant, but these also went away. Although no one knows why they were present in the original study, Dr. Eidelberg suspects it was just an artifact from the small sample size.

FUTURE OF RESEARCH

Right now, Dr. Eidelberg says a European study has just begun further investigating fetal nerve tissue transplants for Parkinson's. The team is using a different approach: instead of planting grafts on the brain, "like hair plugs," Dr. Eidelberg says, they're actually spraying cells over the target region. This technique, as it prevents clumping, will likely drastically reduce any chances of the GID side effects.

But even so, is the treatment something he would recommend to patients now?

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