TY - JOUR
T1 - Progress in progestin-based therapies for neurological disorders
AU - Sitruk-Ware, Regine
AU - Bonsack, Brooke
AU - Brinton, Roberta
AU - Schumacher, Michael
AU - Kumar, Narender
AU - Lee, Jea Young
AU - Castelli, Vanessa
AU - Corey, Sydney
AU - Coats, Alexandreya
AU - Sadanandan, Nadia
AU - Gonzales-Portillo, Bella
AU - Heyck, Matt
AU - Shear, Alex
AU - Blaise, Cozene
AU - Zhang, Henry
AU - Sheyner, Michael
AU - García-Sánchez, Julián
AU - Navarro, Lisset
AU - El-Etr, Martine
AU - De Nicola, Alejandro F.
AU - Borlongan, Cesar V.
N1 - Publisher Copyright:
© 2020
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
KW - Amyotrophic lateral sclerosis
KW - Multiple sclerosis
KW - Nestorone
KW - Progesterone
KW - Spinal cord injury
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=85099252954&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85099252954&partnerID=8YFLogxK
U2 - 10.1016/j.neubiorev.2020.12.007
DO - 10.1016/j.neubiorev.2020.12.007
M3 - Review article
C2 - 33359391
AN - SCOPUS:85099252954
SN - 0149-7634
VL - 122
SP - 38
EP - 65
JO - Neuroscience and Biobehavioral Reviews
JF - Neuroscience and Biobehavioral Reviews
ER -