Allopregnanolone as a Therapeutic to Regenerate the Degenerated Brain

We'll never know if this would be useful post stroke since there is NO STROKE LEADER to go to to update the stroke strategy and start research on these questions. You're screwed as long as we don't have stroke survivors running stroke associations. 

Allopregnanolone as a Therapeutic to Regenerate the Degenerated Brain

• Authors
• Authors and affiliations

• Gerson D. Hernandez
• Roberta Diaz Brinton

• Gerson D. Hernandez
  • 1
• Roberta Diaz Brinton
  • 1
  Email author

1. 1.Center for Innovation in Brain Science, College of MedicineUniversity of ArizonaTucsonUSA

Chapter

First Online: 30 May 2019

Part of the ISGE Series book series (ISGE)

Abstract

Neurosteroids regulate both regeneration and repair systems in the brain. Among this class of molecules, allopregnanolone (Allo) is the first regenerative therapeutic that has been extensively investigated in animal models and more recently in humans for its capacity to promote regeneration in the central and peripheral nervous system. In preclinical analyses, Allo induced generation and survival of new neurons in the hippocampus of aged mice and in transgenic mouse models of Alzheimer’s disease (AD), which was associated with restoration of learning and memory function. Allo is a proliferative factor for both neural stem cells and pre-progenitor oligodendrocytes, increasing both the number of newly generated cells and their survival. Safety characteristics of Allo regulation of neurogenesis indicate that the regenerative system it affects is tightly regulated with closely guarded thresholds for both activation and magnitude of proliferation. In the brain of mice with AD, Allo increased liver X receptor and pregnane X receptor expression, reduced ß-amyloid and microglial activation, and increased markers of white matter generation. Results of preclinical studies indicate that an optimal treatment regimen of Allo to promote endogenous regeneration is one that is administered once per week over the course of several months. Allo dose and frequency of exposure are determining factors regulating its therapeutic efficacy. Previous and current human safety exposure data supported by extensive preclinical efficacy data are strong foundations for the clinical development of Allo as a therapeutic to regenerate the degenerated brain.

Keywords

Neurosteroid Allopregnanolone Neurodegeneration Regeneration Aging brain 

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