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Rapamycin causes regression of astrocytomas in tuberous sclerosis complex

Authors

  • David Neal Franz MD,

    Corresponding author
    1. Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH
    2. Department of Neurology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH
    • Department of Neurology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, ML 2015, Cincinnati, OH 45229-3039
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  • Jennifer Leonard MSN, FNP,

    1. Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH
    2. Department of Neurology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH
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  • Cynthia Tudor MSN, PNP,

    1. Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH
    2. Department of Neurology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH
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  • Gail Chuck BS,

    1. Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH
    2. Department of Neurology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH
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  • Marguerite Care MD,

    1. Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH
    2. Department of Radiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH
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  • Gopalan Sethuraman PhD,

    1. Department of Neuroscience Platform, Eli Lilly & Company, Indianapolis, IN
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  • Argirios Dinopoulos MD,

    1. Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH
    2. Department of Neurology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH
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  • George Thomas PhD,

    1. Department of Genome Science, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH
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  • Kerry R. Crone MD

    1. Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH
    2. Department of Neurosurgery, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH
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Abstract

Objective

Tuberous sclerosis complex (TSC) is a genetic disorder characterized by the formation of hamartomas in multiple organs. Five to 15% of affected individuals display subependymal giant cell astrocytomas, which can lead to substantial neurological and postoperative morbidity due to the production of hydrocephalus, mass effect, and their typical location adjacent to the foramen of Monro. We sought to see whether therapy with oral rapamycin could affect growth or induce regression in astrocytomas associated with TSC.

Methods

Five subjects with clinically definite TSC and either subependymal giant cell astrocytomas (n = 4) or a pilocytic astrocytoma (n = 1) were treated with oral rapamycin at standard immunosuppressive doses (serum levels 5–15ng/ml) from 2.5 to 20 months. All lesions demonstrated growth on serial neuroimaging studies. Magnetic resonance imaging scans were performed before and at regular intervals following initiation of therapy.

Results

All lesions exhibited regression and, in one case, necrosis. Interruption of therapy resulted in regrowth of subependymal giant cell astrocytomas in one patient. Resumption of therapy resulted in further regression. Treatment was well tolerated.

Interpretation

Oral rapamycin therapy can induce regression of astrocytomas associated with TSC and may offer an alternative to operative therapy of these lesions. Ann Neurol 2006

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