The Experts below are selected from a list of 96 Experts worldwide ranked by ideXlab platform
Takashi Ohmoto - One of the best experts on this subject based on the ideXlab platform.
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Stereotactic transplantation of a dopamine-producing capsule into the striatum for treatment of Parkinson disease: a preclinical Primate Study.
Journal of neurosurgery, 2003Co-Authors: Hideyuki Yoshida, Isao Date, Tetsuro Shingo, Kenjiro Fujiwara, Kazuki Kobayashi, Yasuyuki Miyoshi, Takashi OhmotoAbstract:Object. The PC12 cells are well known for their ability to secrete dopamine and levodopa. In multiple animal models encapsulated PC12 cells have been shown to ameliorate parkinsonian symptoms when transplanted into the striatum; this technique is expected to be effective clinically as well. The present Study was performed using nonhuman Primates to ensure that the transplantation of encapsulated PC12 cells is likely to be both safe and effective in human clinical trials. Methods. Unencapsulated or encapsulated PC12 cells were implanted into the brains of Japanese monkeys (Macaca fuscata). Histological and immunocytochemical analyses were performed 1, 2, 4, and 8 weeks posttransplantation on the unencapsulated cells and 2, 4, and 8 weeks after transplantation on the encapsulated cells. The survival of the PC12 cells inside the capsule was determined by measuring the amounts of dopamine and levodopa released from the capsules after removal from the striatum. Magnetic resonance imaging was performed in both ...
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Grafting of encapsulated dopamine-secreting cells in Parkinson's disease: long-term Primate Study.
Cell transplantation, 2000Co-Authors: Isao Date, Tetsuro Shingo, Hideyuki Yoshida, Kenjiro Fujiwara, Kazuki Kobayashi, Takashi OhmotoAbstract:The transplantation of encapsulated dopamine-secreting cells into the striatum represents one potential means of treating Parkinson's disease. The present Study investigated the ability of encapsulated PC12 cells, which are derived from rat pheochromocytoma, to supply L-dopa and dopamine into the Primate brain in the long term and to effect functional improvement in the animals. Following polymer encapsulation, PC12 cells were transplanted into the striatum of hemiparkinsonian monkeys. The secretion of L-dopa and dopamine from the encapsulated cells, the morphology of these cells, the histology of the host striatum surrounding the capsule, and functional changes in the host animals were examined 1, 6, and 12 months after transplantation. Analysis of retrieved capsules revealed that the PC12 cells survived and continued to release L-dopa and dopamine even 12 months after transplantation. The histological response of the host brain surrounding the capsules was minimal and there were no signs of immunological rejection or tumor formation. The physical condition of the host animals was good for 12 months, and hematologic and cerebrospinal fluid analysis revealed that no animals suffered from infection or immunological reaction. These PC12 cell-grafted monkeys showed improvements in hand movements after transplantation, effects that lasted for at least 12 months. These results further support the potential use of this approach for the treatment of Parkinson's disease.
Chad E Bigelow - One of the best experts on this subject based on the ideXlab platform.
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Nonclinical Safety Evaluation of scAAV8-RLBP1 for Treatment of RLBP1 Retinitis Pigmentosa.
Molecular therapy. Methods & clinical development, 2017Co-Authors: Timothy K. Maclachlan, Mark Milton, Oliver C. Turner, Francis Fonyuy Tukov, Vivian W Choi, Jan Penraat, Marie-helene Delmotte, Lydia Michaut, Bruce D Jaffee, Chad E BigelowAbstract:Retinitis pigmentosa is a form of retinal degeneration usually caused by genetic mutations affecting key functional proteins. We have previously demonstrated efficacy in a mouse model of RLBP1 deficiency with a self-complementary AAV8 vector carrying the gene for human RLBP1 under control of a short RLBP1 promoter (CPK850). 1 In this article, we describe the nonclinical safety profile of this construct as well as updated efficacy data in the intended clinical formulation. In Rlbp1 −/− mice dosed at a range of CPK850 levels, a minimum efficacious dose of 3 × 10 7 vg in a volume of 1 μL was observed. For safety assessment in these and Rlbp1 +/+ mice, optical coherence tomography (OCT) and histopathological analysis indicated retinal thinning that appeared to be dose-dependent for both Rlbp1 genotypes, with no qualitative difference noted between Rlbp1 +/+ and Rlbp1 −/− mice. In a non-human Primate Study, RLBP1 mRNA expression was detected and dose dependent intraocular inflammation and retinal thinning were observed. Inflammation resolved slowly over time and did not appear to be exacerbated in the presence of anti-AAV8 antibodies. Biodistribution was evaluated in rats and satellite animals in the non-human Primate Study. The vector was largely detected in ocular tissues and low levels in the optic nerve, superior colliculus, and lateral geniculate nucleus, with limited distribution outside of these tissues. These data suggest that an initial subretinal dose of ∼3 × 10 7 vg/μL CPK850 can safely be used in clinical trials.
Francesca S Boscolo - One of the best experts on this subject based on the ideXlab platform.
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a large scale non human Primate Study of the safety and efficacy of neural stem cells derived from human pluripotent stem cells s7 001
Neurology, 2014Co-Authors: Ruslan Semechkin, Rodolfo Gonzalez, Ibon Garitaonandia, Alina Ostrowska, Tatiana Abramihina, Gerald Wambua, Alexander Noskov, Andrew Crain, Maxim Poustovoitov, Francesca S BoscoloAbstract:OBJECTIVE: Determine the safety profile and efficacy of human parthenogenetic stem cell derived neural stem cells (hpNSCs) in a non-human Primate model of Parkinson’s disease. BACKGROUND: We have previously reported results using animal models of Parkinson’s disease that the implantation of hpNSCs slows down the progression of the disease and significantly increases brain dopamine levels. hpNSCs provide therapeutic benefits by two mechanisms of action: 1) the differentiation into dopaminergic neurons and replacement of neurons lost in PD and 2) secretion of neurotrophic factors that promote host neural repair. Here we present the interim results of a comprehensive efficacy, pharmacology and toxicology Study in MPTP-lesioned monkeys with moderate to severe PD symptoms implanted with hpNSCs. DESIGN/METHODS: hpNSCs were manufactured under cGMP standards and injected bilaterally into the striatum and substantia nigra of twelve immunosuppressed MPTP-lesioned African green monkeys with clinical Parkinsonian symptoms. Behavioral changes and motor movements were assessed based on a Parkinsonian summary score. A healthy behavior score, which is equivalent to the "activities of daily living score" of the Unified Parkinson9s Disease Rating Scale as well as abnormal behavior and dyskinesia using a modified Abnormal Involuntary Movement Scale were recorded. Clinical pathology, necropsy, histopathological analysis of multiple organs and biodistribution of the cells were performed on all experimental animals to determine the safety profile of the implanted hpNSCs. RESULTS: Interim results demonstrate that implantation of hpNSCs is safe and well tolerated by the experimental animals with no abnormal behaviors such as dyskinesia or dystonia. Post-implantation behavioral improvement of the hpNSC-transplanted animals is evaluated against sham vehicle controls. CONCLUSIONS: These results demonstrate the safety and therapeutic benefits of human parthenogenetic stem cell derived neural stem cells and their potential clinical application in Parkinson’s disease. Study Supported by: International Stem Cell Corporation Disclosure: Dr. Semechkin has received personal compensation for activities with International Stem Cell Corporation as an employee. Dr. Semechkin has held stock and/or stock options in International Stem Cell Corporation, which sponsored research in which Dr. Semechkin was involved as an investigator. Dr. Gonzalez has received personal compensation for activities with International Stem Cell Corp. as an employee. Dr. Garitaonandia has received personal compensation for activities with the International Stem Cell Corp. Dr. Ostrowska has received personal compensation for activities with the International Stem Cell Corporation as an employee. Ms. Abramihina has received personal compensation for activities with International Stem Cell Corporation as an employee. Dr. Wambua has received personal compensation for activities with International Stem Cell Corporation as an employee. Dr. Noskov has received personal compensation for activities with International Stem Cell Corporation as an employee. Dr. Crain has nothing to disclose. Dr. Poustovoitov has received personal compensation for activities with the International Stem Cell Organization as an employee. Dr. Boscolo has nothing to disclose. Dr. Laurent has nothing to disclose. Dr. Snyder has nothing to disclose. Dr. Redmond has nothing to disclose.
Hideyuki Yoshida - One of the best experts on this subject based on the ideXlab platform.
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Stereotactic transplantation of a dopamine-producing capsule into the striatum for treatment of Parkinson disease: a preclinical Primate Study.
Journal of neurosurgery, 2003Co-Authors: Hideyuki Yoshida, Isao Date, Tetsuro Shingo, Kenjiro Fujiwara, Kazuki Kobayashi, Yasuyuki Miyoshi, Takashi OhmotoAbstract:Object. The PC12 cells are well known for their ability to secrete dopamine and levodopa. In multiple animal models encapsulated PC12 cells have been shown to ameliorate parkinsonian symptoms when transplanted into the striatum; this technique is expected to be effective clinically as well. The present Study was performed using nonhuman Primates to ensure that the transplantation of encapsulated PC12 cells is likely to be both safe and effective in human clinical trials. Methods. Unencapsulated or encapsulated PC12 cells were implanted into the brains of Japanese monkeys (Macaca fuscata). Histological and immunocytochemical analyses were performed 1, 2, 4, and 8 weeks posttransplantation on the unencapsulated cells and 2, 4, and 8 weeks after transplantation on the encapsulated cells. The survival of the PC12 cells inside the capsule was determined by measuring the amounts of dopamine and levodopa released from the capsules after removal from the striatum. Magnetic resonance imaging was performed in both ...
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Grafting of encapsulated dopamine-secreting cells in Parkinson's disease: long-term Primate Study.
Cell transplantation, 2000Co-Authors: Isao Date, Tetsuro Shingo, Hideyuki Yoshida, Kenjiro Fujiwara, Kazuki Kobayashi, Takashi OhmotoAbstract:The transplantation of encapsulated dopamine-secreting cells into the striatum represents one potential means of treating Parkinson's disease. The present Study investigated the ability of encapsulated PC12 cells, which are derived from rat pheochromocytoma, to supply L-dopa and dopamine into the Primate brain in the long term and to effect functional improvement in the animals. Following polymer encapsulation, PC12 cells were transplanted into the striatum of hemiparkinsonian monkeys. The secretion of L-dopa and dopamine from the encapsulated cells, the morphology of these cells, the histology of the host striatum surrounding the capsule, and functional changes in the host animals were examined 1, 6, and 12 months after transplantation. Analysis of retrieved capsules revealed that the PC12 cells survived and continued to release L-dopa and dopamine even 12 months after transplantation. The histological response of the host brain surrounding the capsules was minimal and there were no signs of immunological rejection or tumor formation. The physical condition of the host animals was good for 12 months, and hematologic and cerebrospinal fluid analysis revealed that no animals suffered from infection or immunological reaction. These PC12 cell-grafted monkeys showed improvements in hand movements after transplantation, effects that lasted for at least 12 months. These results further support the potential use of this approach for the treatment of Parkinson's disease.
Chih-liang Chin - One of the best experts on this subject based on the ideXlab platform.
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Quantification of regional myocardial mean intracellular water lifetime: A nonhuman Primate Study in myocardial stress.
NMR in biomedicine, 2020Co-Authors: Smita Sampath, Annamalai Sarayu Parimal, Wei Huang, Elaine Manigbas, Willy Gsell, M.m.l. Chang, Anqi Qiu, Kirsten Jacobsen, Jeffrey L. Evelhoch, Chih-liang ChinAbstract:Heart failure with preserved ejection fraction (HFpEF) is typically associated with early metabolic remodeling. Noninvasive imaging biomarkers that reflect these changes will be crucial in determining responses to early drug interventions in these patients. Mean intracellular water lifetime (τi ) has been shown to be partially inversely related to Na, K-ATPase transporter activity and may thus provide insight into the metabolic status in HFpEF patients. Here, we aim to perform regional quantification of τi using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in the nonhuman Primate (NHP) heart and evaluate its region-specific variations under conditions of myocardial stress in the context of perturbed myocardial function. Cardiac stress was induced in seven naive cynomolgus macaques using a dobutamine stepwise infusion protocol. All animals underwent 3 T cardiac dual-bolus DCE and tagging MRI experiments. The shutter-speed model was employed to quantify regional τi from the DCE-MR images. Additionally, τi values were correlated with myocardial strains. During cardiac stress, there was a significant decrease in global τi (192.9 ± 76.3 ms vs 321.6 ± 70 ms at rest, P < 0.05) in the left ventricle, together with an increase in global peak circumferential strain (-15.4% ± 2.7% vs -10.1% ± 2.9% at rest, P < 0.05). Specifically, slice-level analysis further revealed that a greater significant decrease in mean τi was observed in the apical region (ΔτI = 182.4 ms) compared with the basal (Δτi = 113.2 ms) and midventricular regions (Δτi = 108.4 ms). Regional analysis revealed that there was a greater significant decrease in mean τi in the anterior (Δτi = 243.9 ms) and antero-lateral (Δτi = 177.2 ms) regions. In the inferior and infero-septal regions, although a decrease in τi was observed, it was not significant. Whole heart regional quantification of τi is feasible using DCE-MRI. τi is sensitive to regional changes in metabolic state during cardiac stress, and its value correlates with strain.