Status of Fetal Tissue Transplantation for the Treatment of Advanced Parkinson Disease

Paul E. Greene, M.D., Stanley Fahn, M.D.

Disclosures

Neurosurg Focus. 2002;13(5) 

In This Article

Commentary on Results of Fetal Tissue Implant Study

The study was a collaboration between the University of Colorado, Columbia-Presbyterian Medical Center, and North Shore University Hospital. We enrolled 40 patients in whom PD had been present at least 7 years and in whom disabling motor symptoms occurred despite optimal pharmacological management. Patients were stratified in advance into two groups: those older than 60 and those 60 years of age or younger at the time of recruitment. Patients were randomized to undergo fetal tissue implantation or sham surgery. A battery of tests was performed at baseline and during the year-long double-blind phase, including off- and on- medication inpatient UPDRS, timed motor tests, and home diaries of drug dosages of off and on states. Patients underwent a blinded fluorodopa PET scanning at baseline and at 1 year after surgery. After the "blind" was broken at 1 year, patients who had undergone the sham procedure had the option of undergoing implantation immediately. One patient who received the implantation during the double-blind phase died 8 months after surgery (motor vehicle accident) and 14 of 20 sham-treated surgery patients returned to undergo the actual fetal tissue implantation. Thus, we gathered double-blind data in 19 patients obtained for the 1-year period after implantation as well as open-label follow-up data these 19 in addition to 14 others (total 33 patients). All patients who had fetal tissue implants continued home and hospital evaluations every 6 months, and PET scans were obtained every 2 years. Details of fetal tissue processing and complete study methods have been previously published.[2]

There was no statistically significant difference between implant-and sham-treated groups in the primary outcome, a subjective comparative global rating determined 1 year after surgery. Placebo-treated patients rated their status as improved by a mean of + 0.3 of a possible ± 3 points, whereas implant-treated patients rated their status as improved by a mean + 0.6 of ± 3 points. Prior to the study, the investigators considered a change of 1.5 of 3 points as clinically meaningful. There were no significant differences in any outcome measures while in the on-medication state for the group as a whole or for either younger or older patients. The total mean UPDRS off-medication score improved more in the implant-treated group (preoperative score of 58 to postoperative score of 50) than in the sham group (from 66 to 63, respectively) and this was of borderline significance (p = 0.055). In addition, other off-state measures (total motor, bradykinesia, and rigidity subscores of the UPDRS) and Schwab and England disability scale scores were significantly more improved in the implant-treated than the sham-treated group (p value range 0.00001-0.017). Significant improvement in these scores, however, occurred only in the group of younger patients, who improved markedly in the off-medication UPDRS total score (60-45), UPDRS motor subscore (from 38-26), rigidity and bradykinesia subscores, and Schwab and England Scale scores compared with the placebo-treated group (p value range 0.0003-0.02). No improved tremor in the off state was evident in either age group. Walking did not improve significantly, based on examination or history, and walking and balance actually worsened in the group of patients older than 60 years of age (p = 0.033). There were no significant differences between implant-and sham-treated patients in either age group in terms of the amount of time off medication, on medication, or on medication without experiencing dyskinesias.

In 12 of 19 implant-treated patients PET scanning demonstrated improvement (≥ 0.2) in striatal/occipital ratio on at least one side of the brain. In sham-treated operated patients no improvement in striatal/occipital ratio of this magnitude was shown. This improvement, however, did not correlate with improvement in parkinsonian ratings in the off-medication state because the older group had a mean PET-documented improvement similar to that observed in the younger group but did not have a comparable improvement in UPDRS scores.

Of considerable concern to us were the five of the 33 implant-treated patients in whom severe dyskinesias and/ or dystonia developed in the absence or near absence of levodopa and dopamine agonists (that is, "runaway" dyskinesias). Two of these patients were able to stop all anti-parkinsonian medications and the involuntary movements persisted. These patients had experienced among the most dramatic improvements. Despite multiple attempts to adjust medications and deep brain stimulation in the globus pallidus in three cases, the involuntary movements continued to be troublesome.

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