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Dr. Okun

New Study: Spheramine Cell Survival Poor after PD Transplant

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Dear Forum Members,


There have been some recent and interesting trials of Spheramine for PD (a transplant surgery where retinal cells are carried to the brain by a gelatin-like carrier). Unfortunately one of the patients died from an unrelated cause and had an autopsy. The autopsy revealed poor cell survival for this therapy in the brain of this patient. These are findings that will be important for us to learn from as we design more rationale therapies....we have to ask ourselves....when we replace cells will they get sick with Parkinson's disease too....below is the abstract from the article by Dr. Bronstein and Farag.


Neurology. 2009 Sep 2. [Epub ahead of print] Links

Pathologic findings in retinal pigment epithelial cell implantation for Parkinson disease.


Farag ES, Vinters HV, Bronstein J.

From the UCLA Department of Neurology (E.S.F., H.V.V., J.B.); WLA VA Southwest PADRECC (E.S.F., J.B.), Los Angeles; and UCLA Section of Neuropathology (H.V.V.), Department of Pathology and Laboratory Medicine, Los Angeles, CA.

BACKGROUND: Attempts at cell-based dopamine replacement therapy in Parkinson disease (PD) have included surgical implantation of adrenal medullary, fetal mesencephalic, and cultured human mesencephalic tissue grafts. Trials involving putamenal implantation of human retinal pigment epithelial (RPE) cells in PD have also been performed. Neuropathologic findings in humans undergoing RPE cell implantation have not heretofore been reported. We describe the brain autopsy findings from a subject enrolled in a clinical trial of RPE cells in gelatin microcarriers for treatment of PD, and suggest factors which may have impacted cell survival. METHODS: A 68-year-old man underwent bilateral surgical implantation of 325,000 RPE cells in gelatin microcarriers (Spheramine) but died 6 months after surgery. The left cerebral hemisphere was examined. Routine postmortem formalin fixation was performed and standard, as well as immunohistochemical methods used to highlight senile plaque and Lewy body pathologic changes, iron deposition, cellular inflammation, and reactive astrocytosis in implant regions. Manual cell counts were done of RPE cells. RESULTS: Hematoxylin-eosin and alpha-synuclein immunostains confirmed the diagnosis of PD. Needle tracts with matrix material and RPE cells were observed in the context of local inflammatory and astrocytic reactive change. A total of 118 cells were counted (estimated 0.036% survival). CONCLUSIONS: Retinal pigment epithelial cells are seen in human brain 6 months postimplantation, but overall survival of implanted cells appeared poor.

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