The Experts below are selected from a list of 267 Experts worldwide ranked by ideXlab platform
Joshua David Rosenberg - One of the best experts on this subject based on the ideXlab platform.
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Informed Consent and Sham Surgery as a Placebo in Fetal Cell Transplant Therapy Research for Parkinson’s Disease
Einstein Journal of Biology and Medicine, 2016Co-Authors: Joshua David RosenbergAbstract:Fetal cellular Transplantation therapy research in Parkinson’s Disease has raised important ethical questions from its beginning. One of the most hotly debated aspects of the recent clinical research has been the use of sham surgery as a placebo for the control group. Ethicists and researchers have focused on the unique risk surgical placebos pose to research subjects as compared to conventional, medical placebos. This review will deal with informed consent and the use of use of sham surgery in the placebo arm of recent Fetal Tissue Transplantation randomized, placebo controlled, double blind, clinical trials. Do current procedures for obtaining informed consent meet the challenge of adequately informing patients enrolling in experiments with significant risks not only in the experimental group but also in the placebo group?
Cesario V. Borlongan - One of the best experts on this subject based on the ideXlab platform.
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Fetal-Tissue Transplantation for Huntington’s Disease: Preclinical Studies
Cell Transplantation for Neurological Disorders, 1998Co-Authors: Paul R. Sanberg, Cesario V. Borlongan, Klas Wictorin, Ole IsacsonAbstract:Huntington’s disease (HD) is a neurodegenerative disorder transmitted by a single autosomal dominant gene. This normally occurring Huntington gene is mutated in HD. This HD mutation involves an unstable DNA segment; the IT15 gene, which is located near the telomere of the short arm of chromosome 4, contains a trinucleotide repeat (CAG) that is expanded (> 36) and unstable (1). Clinically, HD is characterized by constant, uncontrollable choreiform movements of the body coupled with progressive deterioration of the patient’s mental status (2,3), which ultimately leads to death.
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Fetal Tissue Transplantation for huntington s disease preclinical studies
1998Co-Authors: Paul R. Sanberg, Cesario V. Borlongan, Klas Wictorin, Ole IsacsonAbstract:Huntington’s disease (HD) is a neurodegenerative disorder transmitted by a single autosomal dominant gene. This normally occurring Huntington gene is mutated in HD. This HD mutation involves an unstable DNA segment; the IT15 gene, which is located near the telomere of the short arm of chromosome 4, contains a trinucleotide repeat (CAG) that is expanded (> 36) and unstable (1). Clinically, HD is characterized by constant, uncontrollable choreiform movements of the body coupled with progressive deterioration of the patient’s mental status (2,3), which ultimately leads to death.
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Neural Transplantation as an Experimental Treatment Modality for Cerebral Ischemia
Neuroscience & Biobehavioral Reviews, 1997Co-Authors: Cesario V. Borlongan, Jeffrey R. Jorden, Stephen G. Poulos, Peter Mckeown, Alba I Rodriguez, Rodrigo Martínez, T K Koutouzis, Thomas B Freeman, David W. Cahill, Hitoo NishinoAbstract:Abstract BORLONGAN, C. V., T. K. KOUTOUZIS, J. R. JORDEN, R. MARTINEZ, A. I. RODRIGUEZ, S. G. POULOS, T. B. FREEMAN, P. MCKEOWN, D. W. CAHILL, H. NISHINO AND P. R. SANBERG. Neural Transplantation as an experimental treatment modality for cerebral ischemia . NEUROSCI BIOBEHAV REV 21 (1) 79–90, 1997.—Cerebrovascular disease exemplifies the poor regenerative capacity of the CNS. While there are methods to prevent cerebral infarction, there is no effective therapy available to ameliorate the anatomical, neurochemical and behavioral deficits which follow cerebral ischemia. Focal and transient occlusion of the middle cerebral artery (MCA) in rodents has been reported to result in neuropathology similar to that seen in clinical cerebral ischemia. Using specific techniques, this MCA occlusion can result in a well-localized infarct of the striatum. This review article will provide data accumulated from animal studies using the MCA occlusion technique in rodents to examine whether neural Transplantation can ameliorate behavioral and morphological deficits associated with cerebral infarction. Recent advances in neural Transplantation as a treatment modality for neurodegenerative disorders such as Parkinson's disease, have revealed that Fetal Tissue Transplantation may produce neurobehavioral recovery. Accordingly, Fetal Tissue Transplantation may provide a potential therapy for cerebral infarction. Preliminary findings in rodents subjected to unilateral MCA occlusion, and subsequently transplanted with Fetal striatal Tissue into the infarcted striatum have produced encouraging results. Transplanted Fetal Tissue, assessed immunohistochemically, has been demonstrated to survive and integrate with the host Tissue, and, more importantly, ameliorate the ischemia-related behavioral deficits, at least in the short term. Although this review will focus primarily on cerebral ischemia, characterized by a localized CNS lesion within the striatum, it is envisioned that this baseline data may be extrapolated and applied to cerebral infarction in other brain areas. Copyright © 1996 Elsevier Science Ltd.
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neural Transplantation as an experimental treatment modality for cerebral ischemia
Neuroscience & Biobehavioral Reviews, 1997Co-Authors: Cesario V. Borlongan, Jeffrey R. Jorden, Stephen G. Poulos, Peter Mckeown, Alba I Rodriguez, Rodrigo Martínez, T K Koutouzis, Thomas B Freeman, David W. Cahill, Hitoo NishinoAbstract:Cerebrovascular disease exemplifies the poor regenerative capacity of the CNS. While there are methods to prevent cerebral infarction, there is no effective therapy available to ameliorate the anatomical, neurochemical and behavioral deficits which follow cerebral ischemia. Focal and transient occlusion of the middle cerebral artery (MCA) in rodents has been reported to result in neuropathology similar to that seen in clinical cerebral ischemia. Using specific techniques, this MCA occlusion can result in a well-localized infarct of the striatum. This review article will provide data accumulated from animal studies using the MCA occlusion technique in rodents to examine whether neural Transplantation can ameliorate behavioral and morphological deficits associated with cerebral infarction. Recent advances in neural Transplantation as a treatment modality for neurodegenerative disorders such as Parkinson's disease, have revealed that Fetal Tissue Transplantation may produce neurobehavioral recovery. Accordingly, Fetal Tissue Transplantation may provide a potential therapy for cerebral infarction. Preliminary findings in rodents subjected to unilateral MCA occlusion, and subsequently transplanted with Fetal striatal Tissue into the infarcted striatum have produced encouraging results. Transplanted Fetal Tissue, assessed immunohistochemically, has been demonstrated to survive and integrate with the host Tissue, and, more importantly, ameliorate the ischemia-related behavioral deficits, at least in the short term. Although, this review will focus primarily on cerebral ischemia, characterized by a localized CNS lesion within the striatum, it is envisioned that this baseline data may be extrapolated and applied to cerebral infarction in other brain areas.
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bilateral Fetal nigral Transplantation into the postcommissural putamen in parkinson s disease
Annals of Neurology, 1995Co-Authors: Thomas B Freeman, Cesario V. Borlongan, Paul R. Sanberg, Robert A. Hauser, Warren C Olanow, Michael G Nauert, Donald A Smith, Douglas A Holt, Jeffrey H Kordower, Francois J G VingerhoetsAbstract:We performed Fetal nigral Transplantations in 4 Parkinson's disease (PD) patients. Solid grafts were bilaterally implanted into the postcommissural putamen using 3 to 4 donors per side aged 6 1/2 to 9 weeks postconception. Transplant deposits were separated by no more than 5 mm in three dimensions. Cyclosporine was employed for a total of 6 months. Patients were evaluated at baseline and at 1, 3, and 6 months postoperatively. Striatal 18-fluorodopa uptake was assessed by positron emission tomography at baseline and at 6 months postoperatively. The procedure was well tolerated in all patients. One patient had a clinically asymptomatic superficial cortical hemorrhage along the needle tract and a second had transient postoperative confusion and hallucinations. All patients experienced clinically meaningful benefit. Significant improvement (p < 0.05) was detected in total UPDRS score during the „off” state, Schwab-England disability score during the „off” state, percent „off” time, and percent „on” time with dyskinesia. Increased striatal fluorodopa uptake was observed bilaterally in each patient, with mean increases of 53% on the right (p = 0.01) and 33% on the left (p = 0.08). Our study demonstrated clear and consistent improvement in clinical features and striatal fluorodopa uptake following Fetal Tissue Transplantation in patients with advanced PD whose condition was not improved preoperatively by drug manipulation. These preliminary results are encouraging and support further studies to evaluate grafting strategies as a therapy for PD.
Joseph B. Kadane - One of the best experts on this subject based on the ideXlab platform.
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Placebos that harm: sham surgery controls in clinical trials.
Statistical methods in medical research, 2002Co-Authors: Alex John London, Joseph B. KadaneAbstract:Recent debates over the use of sham surgery as a control for studies of Fetal Tissue Transplantation for Parkinson's disease have focused primarily on rival interpretations of the US federal regulations governing human-subjects research. Using the core ethical and methodological considerations that underwrite the equipoise requirement, we find strong prima facie reasons against using sham surgery as a control in studies of cellular-based therapies for Parkinson's disease and more broadly in clinical research. Additionally, we believe that these reasons can be generalized to apply to the use of other placebo controls that carry significant risks of positive harms in and of themselves. As a result, our arguments are centrally relevant to the emerging drive to subject therapies with a surgical component to the same rigorous standards of evaluation as those governing the approval of new pharmaceuticals.
Edward D. Clarkson - One of the best experts on this subject based on the ideXlab platform.
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Fetal Tissue Transplantation for Patients with Parkinson’s Disease
Drugs & Aging, 2001Co-Authors: Edward D. ClarksonAbstract:Over the past 13 years approximately 300 patients with Parkinson’s disease have received transplants of human Fetal dopamine cells in an attempt to reduce or control disease symptoms. Many of these patients have had improvements in their motor skills and a reduction in their daily levodopa administration. However, improvements are far from guaranteed and questions need to be answered before this technique can be widely applied. To help address some of these issues, a search of all the published results of patients with Parkinson’s disease transplanted with human Fetal Tissue was conducted. This generated a database of 70 transplant recipients who had their levodopa administration and clinical benefit reported both prior to transplant and at least 6 months post-transplant. Furthermore, the number of years of disease onset prior to transplant was available for all recipients. This database was examined for motor improvement and reduction in levodopa dosage for up to 2 years post-transplant to determine the effects of time on transplant outcome. The database showed that most recipients had significant improvements in motor skills and levodopa administration, and that most benefits were observed in the first 6 months post-transplant. In addition, the database demonstrated that the number of years of disease onset prior to Transplantation was not a predictor of patient outcome 1-year post-transplant. Current and future directions in Fetal Tissue Transplantation research and replacements for Fetal Tissue are discussed.
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Fetal Tissue Transplantation for patients with Parkinson's disease: a database of published clinical results.
Drugs & aging, 2001Co-Authors: Edward D. ClarksonAbstract:Over the past 13 years approximately 300 patients with Parkinson's disease have received transplants of human Fetal dopamine cells in an attempt to reduce or control disease symptoms. Many of these patients have had improvements in their motor skills and a reduction in their daily levodopa administration. However, improvements are far from guaranteed and questions need to be answered before this technique can be widely applied. To help address some of these issues, a search of all the published results of patients with Parkinson's disease transplanted with human Fetal Tissue was conducted. This generated a database of 70 transplant recipients who had their levodopa administration and clinical benefit reported both prior to transplant and at least 6 months post-transplant. Furthermore, the number of years of disease onset prior to transplant was available for all recipients. This database was examined for motor improvement and reduction in levodopa dosage for up to 2 years post-transplant to determine the effects of time on transplant outcome. The database showed that most recipients had significant improvements in motor skills and levodopa administration, and that most benefits were observed in the first 6 months post-transplant. In addition, the database demonstrated that the number of years of disease onset prior to Transplantation was not a predictor of patient outcome 1-year post-transplant. Current and future directions in Fetal Tissue Transplantation research and replacements for Fetal Tissue are discussed.
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Development of Fetal neural Transplantation as a treatment for Parkinson's disease
Life sciences, 1999Co-Authors: Edward D. Clarkson, Curt R. FreedAbstract:Abstract Since 1988, patients with Parkinson's disease have participated in clinical trials evaluating the efficacy of Transplantation of human Fetal dopamine cells into the caudate and putamen. Transplantation of Fetal Tissue leads to clinical benefits in some patients which is associated with a reduction of the amount of L-DOPA administered. Major issues in transplant research need to be addressed before this technique can be widely applied. In this review, a pool of 35 patients was generated from the published cases of human Fetal Tissue Transplantation. This group of transplant recipients was examined for motor improvement and reduction in L-DOPA dosage at one year post-transplant. Issues addressed in this review include the benefits of unilateral vs bilateral Transplantation, age of the transplant recipient, solid vs suspensions of Fetal mesencephalon and the number of Fetal donors per recipient.
Thomas B Freeman - One of the best experts on this subject based on the ideXlab platform.
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Neural Transplantation in Parkinson's Disease
Advances in neurology, 2001Co-Authors: Thomas B Freeman, Paul R. Sanberg, A E Willing, T. Zigova, Robert A. HauserAbstract:In conclusion, proof of the principle exists that neural grafts can survive Transplantation in PD and that this graft survival is related to preliminary evidence of clinical benefit and improvement on FD-PET. Two prospective, randomized, surgical placebo-controlled trials of Fetal Tissue Transplantation for the treatment of PD will be published in the near future, as will results of a placebo-controlled xenograft trial. Lifelong survival of human Fetal nigral grafts is likely. The striatum is comparatively simple to target surgically in comparison to other sites such as the subthalamic nucleus. Several new sources of dopamine cells are being developed for Transplantation purposes. Long-term monitoring for toxicity, such as the development of dyskinesias, will be needed, and dose-escalation trials should be performed slowly due to the irreversible nature of transplants. There are numerous ways to improve current techniques of neural Transplantation.
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Neural Transplantation as an Experimental Treatment Modality for Cerebral Ischemia
Neuroscience & Biobehavioral Reviews, 1997Co-Authors: Cesario V. Borlongan, Jeffrey R. Jorden, Stephen G. Poulos, Peter Mckeown, Alba I Rodriguez, Rodrigo Martínez, T K Koutouzis, Thomas B Freeman, David W. Cahill, Hitoo NishinoAbstract:Abstract BORLONGAN, C. V., T. K. KOUTOUZIS, J. R. JORDEN, R. MARTINEZ, A. I. RODRIGUEZ, S. G. POULOS, T. B. FREEMAN, P. MCKEOWN, D. W. CAHILL, H. NISHINO AND P. R. SANBERG. Neural Transplantation as an experimental treatment modality for cerebral ischemia . NEUROSCI BIOBEHAV REV 21 (1) 79–90, 1997.—Cerebrovascular disease exemplifies the poor regenerative capacity of the CNS. While there are methods to prevent cerebral infarction, there is no effective therapy available to ameliorate the anatomical, neurochemical and behavioral deficits which follow cerebral ischemia. Focal and transient occlusion of the middle cerebral artery (MCA) in rodents has been reported to result in neuropathology similar to that seen in clinical cerebral ischemia. Using specific techniques, this MCA occlusion can result in a well-localized infarct of the striatum. This review article will provide data accumulated from animal studies using the MCA occlusion technique in rodents to examine whether neural Transplantation can ameliorate behavioral and morphological deficits associated with cerebral infarction. Recent advances in neural Transplantation as a treatment modality for neurodegenerative disorders such as Parkinson's disease, have revealed that Fetal Tissue Transplantation may produce neurobehavioral recovery. Accordingly, Fetal Tissue Transplantation may provide a potential therapy for cerebral infarction. Preliminary findings in rodents subjected to unilateral MCA occlusion, and subsequently transplanted with Fetal striatal Tissue into the infarcted striatum have produced encouraging results. Transplanted Fetal Tissue, assessed immunohistochemically, has been demonstrated to survive and integrate with the host Tissue, and, more importantly, ameliorate the ischemia-related behavioral deficits, at least in the short term. Although this review will focus primarily on cerebral ischemia, characterized by a localized CNS lesion within the striatum, it is envisioned that this baseline data may be extrapolated and applied to cerebral infarction in other brain areas. Copyright © 1996 Elsevier Science Ltd.
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neural Transplantation as an experimental treatment modality for cerebral ischemia
Neuroscience & Biobehavioral Reviews, 1997Co-Authors: Cesario V. Borlongan, Jeffrey R. Jorden, Stephen G. Poulos, Peter Mckeown, Alba I Rodriguez, Rodrigo Martínez, T K Koutouzis, Thomas B Freeman, David W. Cahill, Hitoo NishinoAbstract:Cerebrovascular disease exemplifies the poor regenerative capacity of the CNS. While there are methods to prevent cerebral infarction, there is no effective therapy available to ameliorate the anatomical, neurochemical and behavioral deficits which follow cerebral ischemia. Focal and transient occlusion of the middle cerebral artery (MCA) in rodents has been reported to result in neuropathology similar to that seen in clinical cerebral ischemia. Using specific techniques, this MCA occlusion can result in a well-localized infarct of the striatum. This review article will provide data accumulated from animal studies using the MCA occlusion technique in rodents to examine whether neural Transplantation can ameliorate behavioral and morphological deficits associated with cerebral infarction. Recent advances in neural Transplantation as a treatment modality for neurodegenerative disorders such as Parkinson's disease, have revealed that Fetal Tissue Transplantation may produce neurobehavioral recovery. Accordingly, Fetal Tissue Transplantation may provide a potential therapy for cerebral infarction. Preliminary findings in rodents subjected to unilateral MCA occlusion, and subsequently transplanted with Fetal striatal Tissue into the infarcted striatum have produced encouraging results. Transplanted Fetal Tissue, assessed immunohistochemically, has been demonstrated to survive and integrate with the host Tissue, and, more importantly, ameliorate the ischemia-related behavioral deficits, at least in the short term. Although, this review will focus primarily on cerebral ischemia, characterized by a localized CNS lesion within the striatum, it is envisioned that this baseline data may be extrapolated and applied to cerebral infarction in other brain areas.
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bilateral Fetal nigral Transplantation into the postcommissural putamen in parkinson s disease
Annals of Neurology, 1995Co-Authors: Thomas B Freeman, Cesario V. Borlongan, Paul R. Sanberg, Robert A. Hauser, Warren C Olanow, Michael G Nauert, Donald A Smith, Douglas A Holt, Jeffrey H Kordower, Francois J G VingerhoetsAbstract:We performed Fetal nigral Transplantations in 4 Parkinson's disease (PD) patients. Solid grafts were bilaterally implanted into the postcommissural putamen using 3 to 4 donors per side aged 6 1/2 to 9 weeks postconception. Transplant deposits were separated by no more than 5 mm in three dimensions. Cyclosporine was employed for a total of 6 months. Patients were evaluated at baseline and at 1, 3, and 6 months postoperatively. Striatal 18-fluorodopa uptake was assessed by positron emission tomography at baseline and at 6 months postoperatively. The procedure was well tolerated in all patients. One patient had a clinically asymptomatic superficial cortical hemorrhage along the needle tract and a second had transient postoperative confusion and hallucinations. All patients experienced clinically meaningful benefit. Significant improvement (p < 0.05) was detected in total UPDRS score during the „off” state, Schwab-England disability score during the „off” state, percent „off” time, and percent „on” time with dyskinesia. Increased striatal fluorodopa uptake was observed bilaterally in each patient, with mean increases of 53% on the right (p = 0.01) and 33% on the left (p = 0.08). Our study demonstrated clear and consistent improvement in clinical features and striatal fluorodopa uptake following Fetal Tissue Transplantation in patients with advanced PD whose condition was not improved preoperatively by drug manipulation. These preliminary results are encouraging and support further studies to evaluate grafting strategies as a therapy for PD.
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Cell Transplantation for central nervous system disorders.
Critical reviews in neurobiology, 1994Co-Authors: T K Koutouzis, Thomas B Freeman, Cesario V. Borlongan, David W. Cahill, Dwaine F. Emerich, Paul R. SanbergAbstract:Initially, the specific aim of Transplantation studies was to investigate the regenerative capabilities of the mammalian nervous system. From this underlying impetus, a myriad of knowledge, spanning from molecular biology to neurobiology, has enhanced our understanding of regeneration and the applicability of Fetal Tissue Transplantation in treating various neurodegenerative diseases. Current evidence suggests that Transplantation of Fetal neural Tissue ameliorates the neurobiological and behavioral changes observed in animal models of central nervous system (CNS) disorders. In light of numerous basic science studies, clinical trials have begun to evaluate the potential of neural Transplantation in treating human diseases. Indeed, modest progress has been reported in the treatment of Parkinson's disease. However, whereas Fetal Tissue Transplantation has reached considerable success, it has also been observed to produce either no beneficial effects, magnify existing behavioral abnormalities, or even produce a unique constellation of deficits. Thus, while the prospects are promising, further investigations aimed at improving and refining existing Transplantation paradigms are warranted before neural Transplantation techniques can be of widespread value. This review article attempts to provide an overview of the neuroanatomical, neurochemical, and behavioral effects produced by transplanted Fetal Tissue in several animal models of CNS disorders. We have attempted to present both positive and adverse effects and to critically analyze the suitability of neural Transplantation as a therapy for the various neurological disorders. In addition, alternative approaches, including the use of encapsulated neural Tissue implants and genetically engineered cell lines along with their clinical potential, are discussed when appropriate.