Towards cell replacement therapy in Parkinson’s disease. Proteoglycans and Nogo-A as modulators of axonal growth in midbrain dopaminergic neurons
type: CreativeWork
description: Parkinson’s disease (PD) is currently the second most common neurodegenerative disorder (after Alzheimer’s disease). PD is diagnosed on its motor symptoms, which include akinesia, bradykinesia, rigidity, postural imbalance and resting tremor. It is well established that the motor symptoms develop due to lack of dopamine in the striatum. This is caused by progressive degeneration of dopaminergic neurons (DNs) in the midbrain (substantia nigra pars compacta), which innervate the striatum. Although initially efficacious, the therapeutic effect of various anti-parkinsonian pharmacological treatments is limited to five to ten years. Hence, the new therapeutic strategies for PD are highly warranted. The concept of cell replacement therapy in PD is based on the idea that the diminished dopamine levels in the striatum would be restored by the functional DNs, obtained from donated, electively aborted fetuses, and subsequently injected into the patients’ striatum. In several clinical trials, about 400 patients received such therapy worldwide. Although the therapeutic effects varied, some individuals experienced major motor improvement even for up to 16 years. Other PD patients did not respond so favorably and even developed adverse effects, i.e. graft-induced dyskinesia. The clinical trials are currently on hold. In the first project, we have analyzed the survival and integration of the graft in a patient who underwent the transplantation in Lund, in 1987, as one of the first transplanted cases in the world. Clinically, the patient did not show the symptomatic relief in response to the transplantation. Examining the postmortem brain, we observed a very small surviving graft. In addition, we also detected signs of PD-like pathology in the transplanted DNs. Nonetheless, the graft survived in this brain for 22 years and such a long graft-life has never before been reported. It is certain that embryonic tissue will not be routinely used as a cell source for transplantation therap…
abstract: Parkinson’s disease (PD) is currently the second most common neurodegenerative disorder (after Alzheimer’s disease). PD is diagnosed on its motor symptoms, which include akinesia, bradykinesia, rigidity, postural imbalance and resting tremor. It is well established that the motor symptoms develop due to lack of dopamine in the striatum. This is caused by progressive degeneration of dopaminergic neurons (DNs) in the midbrain (substantia nigra pars compacta), which innervate the striatum. Although initially efficacious, the therapeutic effect of various anti-parkinsonian pharmacological treatments is limited to five to ten years. Hence, the new therapeutic strategies for PD are highly warranted. The concept of cell replacement therapy in PD is based on the idea that the diminished dopamine levels in the striatum would be restored by the functional DNs, obtained from donated, electively aborted fetuses, and subsequently injected into the patients’ striatum. In several clinical trials, about 400 patients received such therapy worldwide. Although the therapeutic effects varied, some individuals experienced major motor improvement even for up to 16 years. Other PD patients did not respond so favorably and even developed adverse effects, i.e. graft-induced dyskinesia. The clinical trials are currently on hold. In the first project, we have analyzed the survival and integration of the graft in a patient who underwent the transplantation in Lund, in 1987, as one of the first transplanted cases in the world. Clinically, the patient did not show the symptomatic relief in response to the transplantation. Examining the postmortem brain, we observed a very small surviving graft. In addition, we also detected signs of PD-like pathology in the transplanted DNs. Nonetheless, the graft survived in this brain for 22 years and such a long graft-life has never before been reported. It is certain that embryonic tissue will not be routinely used as a cell source for transplantation therap…
author: Kurowska, Zuzanna
language: eng
keywords: Neurosciences, LUHMES cells, substantia nigra pars compacta, microarray, heparan sulphate 3-O-sulfotransferase, neurocan, midbrain dopaminergic neurons, grafting, embryonic stem cells, proteoglycans, glycosaminoglycans, Nogo-A, cell replacement therapy, Parkinson’s disease
date published: 2012
date modified: 2026-07-24T02:59:49Z
provider: University of Lund
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Department of Experimental Medical Science, Lund Univeristy