Progress in progestin-based therapies for neurological disorders

Regine Sitruk-Ware, Brooke Bonsack, Roberta Brinton, Michael Schumacher, Narender Kumar, Jea Young Lee, Vanessa Castelli, Sydney Corey, Alexandreya Coats, Nadia Sadanandan, Bella Gonzales-Portillo, Matt Heyck, Alex Shear, Cozene Blaise, Henry Zhang, Michael Sheyner, Julián García-Sánchez, Lisset Navarro, Martine El-Etr, Alejandro F. De NicolaCesar V. Borlongan

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations

Abstract

Hormone therapy, primarily progesterone and progestins, for central nervous system (CNS) disorders represents an emerging field of regenerative medicine. Following a failed clinical trial of progesterone for traumatic brain injury treatment, attention has shifted to the progestin Nestorone for its ability to potently and selectively transactivate progesterone receptors at relatively low doses, resulting in robust neurogenetic, remyelinating, and anti-inflammatory effects. That CNS disorders, including multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), spinal cord injury (SCI), and stroke, develop via demyelinating, cell death, and/or inflammatory pathological pathways advances Nestorone as an auspicious candidate for these disorders. Here, we assess the scientific and clinical progress over decades of research into progesterone, progestins, and Nestorone as neuroprotective agents in MS, ALS, SCI, and stroke. We also offer recommendations for optimizing timing, dosage, and route of the drug regimen, and identifying candidate patient populations, in advancing Nestorone to the clinic.

Original languageEnglish (US)
Pages (from-to)38-65
Number of pages28
JournalNeuroscience and Biobehavioral Reviews
Volume122
DOIs
StatePublished - Mar 2021
Externally publishedYes

Keywords

  • Amyotrophic lateral sclerosis
  • Multiple sclerosis
  • Nestorone
  • Progesterone
  • Spinal cord injury
  • Stroke

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

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