PD: Fetal transplants (AAN report)

Subject: PD: Fetal transplants (AAN report)

Date: 4/30/1999

1. Double-blind controlled trial of human embryonic dopamine cell transplants in advanced Parkinson's disease: Study design, surgical strategy, patient demographics, and pathological outcome
CR Freed, RE Breeze, PE Greene, WY Tsai, D Eidelberg, JQ Trojanowski, JM Rosenstein, S Fahn
Neurology 1999;52(Suppl 2):A272-273

2. Double-blind controlled trial of human embryonic dopamine tissue transplants in advanced Parkinson's disease: Clinical outcomes
S Fahn, PE Greene, WY Tsai, D Eidelberg, H Winfield, S Dillon, R Kao, L Winfield, RE Breeze, CR Freed
Neurology 1999;52(Suppl 2):A405

3. Double-blind controlled trial of human embryonic dopamine tissue transplants in advanced Parkinson's disease: Long-term unblinded follow-up phase
PE Greene, S Fahn, WY Tsai, H Winfield, S Dillon, R Kao, L Winfield, D Eidelberg, RE Breeze, CR Freed
Neurology 1999;52(Suppl 2):A405

4. Double-blind controlled trial of human embryonic dopamine tissue transplants in advanced Parkinson's disease: Fluorodopa PET imaging
V Dhawan, T Akamura, C Margouleff, CR Freed, RE Breeze, S Fahn, PE Greene, WY Tsai, R Kao, D Eidelberg
Neurology 1999;52(Suppl 2):A405-406

Results from the first double-blind placebo-controlled trial of fetal graft transplantation surgery for advanced Parkinson's disease show the greatest treatment benefit in younger patients and on rigidity and bradykinesia.

Forty patients (half under age 60) with duration of at least 7 years who were still levodopa-responsive but with motor fluctuations, were randomized to receive either placebo (4 drill holes to the forehead without dural penetration) or 4 embryonic mesencephalons delivered via 4 needle passes to the left and right putamens. Assessments included clinical evaluation with the UPDRS and other measures at 4, 8, and 12 months post-surgery, and analysis of home videotapes of a mini-UPDRS before and after morning levodopa. The blind was broken after one year, and placebo patients were offered transplant surgery.

One-year results indicate significant improvements in rigidity and bradykinesia in younger (<age 60), but not older patients. No significant improvements were seen in freezing gait. During his platform presentation, Dr. Fahn noted, "These results suggest that dopa-responsive freezing gait is not related to decreased dopaminergic activity in the putamen. The anatomical site responsible for freezing remains to be determined." Significant adverse events were more common in the treatment group, although these were not thought to be related to treatment.

Autopsies of two treated patients who died from unrelated causes showed large numbers of tyrosine hydroxylase-positive cells along the needle tracks, with long cell processes extending into the surrounding putamen, and minimal inflammation.

In the unblinded follow-up, wide variation was seen in treated patient outcomes. Mean daily dose of levodopa or equivalents declined steadily following treatment, from a mean of 959 mg/day to 705 mg/day after 30 months (in the 5 patients followed this long). Several patients developed significant motor complications more than one year after surgery, including one patient with dyskinesias while off levodopa. In his poster presentation, Dr. Greene noted "Disabling dyskinesias/dystonias and frequent brief "off" periods...may limit the usefulness of this procedure."

E-MOVE Editor: Richard Robinson, NASW, WE MOVE

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