Grafts of Fetal Dopamine Neurons Survive and Improve Motor Function in Parkinson's Disease

Abstract

Neural transplantation can restore striatal dopaminergic neurotransmission in animal models of Parkinson's disease. It has now been shown that mesencephalic dopamine neurons, obtained from human fetuses of 8 to 9 weeks gestational age, can survive in the human brain and produce marked and sustained symptomatic relief in a patient severely affected with idiopathic Parkinson's disease. The grafts, which were implanted unilaterally into the putamen by stereotactic surgery, restored dopamine synthesis and storage in the grafted area, as assessed by positron emission tomography with 6-L-[18F]fluorodopa. This neurochemical change was accompanied by a therapeutically significant reduction in the patient's severe rigidity and bradykinesia and a marked diminuation of the fluctuations in the patient's condition during optimum medication (the "on-off" phenomenon). The clinical improvement was most marked on the side contralateral to the transplant.

Expansion of Human Neural Precursor Cells in Large‐Scale Bioreactors for the Treatment of Neurodegenerative Disorders

“…Previous studies have shown that cell replacement therapy using fetal tissue may be a viable treatment option for PD [4][5][6][7][8] and HD. [9][10][11][12] In the case of PD, two double-blind studies sponsored by National Institutes of Health (NIH) found that the transplantation of fetal DA neurons into the brain of PD patients resulted in modest functional benefits but also caused undesirable side effects.…”

Cell Therapeutics in Parkinson's Disease

“…Dopaminergic Grafts Can Survive and Become Morphologically Integrated in the PD Patient's Brain Following implantation of postmitotic DA neuroblasts from the ventral mesencephalon of 6-to 9-weekold human fetuses, positron emission tomography (PET) detected increases in 6-L-[ 18 F]-fluorodopa ( 18 F-dopa) uptake ( Fig. 1) [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19], and histopathological studies have shown long-term, extensive synaptic reinnervation in the striatum [13,[20][21][22][23][24][25][26][27].…”

Dopamine Cell Transplantation for Parkinson's Disease: The Importance of Controlled Clinical Trials

“…Unilateral transplantation of fetal tissue was used in the first human clinical Parkinson's disease transplant trials [3,4,38]. Typically implants were made into the side of brain contralateral to the side of the body with the worse Parkinson's symptoms.…”

“…Therefore, we did not use immunosuppression in our double-blind transplant study [7]. The Lund group chose to use immunosuppressants at doses equivalent to those given to kidney transplant patients [4]. When Freeman et al [43] and Olanow et al [9] started their transplant program approximately 5 years after our group and the Lund group, they took a middle ground, using short-term immunosuppression of 6 to 18 months.…”

“…For human transplantation, the equivalent stage of embryonic development is 6 to 8 weeks after conception [3][4][5]. All successful allografts of human embryonic tissue into patients with Parkinson's disease have come from tissue in this developmental window.…”