Overview of Neurosteroids in Various CNS Indications
- MacKenzie G, Maguire J. Neurosteroids and GABAergic signaling in health and disease. Biomol Concepts. 2013;4(1):29-42. doi:10.1515/bmc-2012-0033
- Zorumski CF, Paul SM, Izumi Y, Covey DF, Mennerick S. Neurosteroids, stress and depression: Potential therapeutic opportunities. Neurosci Biobehav Rev. 2013;37(1):109-122. doi:10.1016/j.neubiorev.2012.10.005
- Reddy DS. Role of hormones and neurosteroids in epileptogenesis. Front Cell Neurosci. 2013;7(July):1-20. doi:10.3389/fncel.2013.00115
Ganaxolone Mechanism of Action
- Carter RB, Wood PL, Wieland S, et al. Characterization of the Anticonvulsant Properties of Ganaxolone (CCD 1042; 3α-Hydroxy-3β-methyl-5α-pregnan-20-one), a Selective, High-Affinity, Steroid Modulator of the γ-Aminobutyric AcidA Receptor. J Pharmacol Exp Ther. 1997;280(3):1284-1295. - http://jpet.aspetjournals.org/content/280/3/1284.abstract.
- Nik AM, Pressly B, Singh V, et al. Rapid Throughput Analysis of GABA A Receptor Subtype Modulators and Blockers Using DiSBAC 1 (3) Membrane Potential Red Dye. Mol Pharmacol. 2017;92(1):88-99. doi:10.1124/mol.117.108563.
- Chuang S-H, Reddy DS. 3β-Methyl-Neurosteroid Analogs are Preferential Positive Allosteric Modulators and Direct Activators of Extrasynaptic δGABA-A Receptors in the Hippocampus Dentate Gyrus Subfield. J Pharmacol Exp Ther. 2018;246660:jpet.117.246660. doi:10.1124/jpet.117.246660
Background on CDKL5 Deficiency Disorder
- Fehr S, Wong K, Chin R, et al. Seizure variables and their relationship to genotype and functional abilities in the CDKL5 disorder. Neurology. 2016;87(21):2206-2213. doi:10.1212/WNL.0000000000003352
- Mangatt M, Wong K, Anderson B, et al. Prevalence and onset of comorbidities in the CDKL5 disorder differ from Rett syndrome. Orphanet J Rare Dis. 2016;11(1). doi:10.1186/s13023-016-0418-y
- Müller A, Helbig I, Jansen C, et al. Retrospective evaluation of low long-term efficacy of antiepileptic drugs and ketogenic diet in 39 patients with CDKL5-related epilepsy. Eur J Paediatr Neurol. 2016;20(1):147-151. doi:10.1016/j.ejpn.2015.09.001
- Specchio N, Chez M, Tarquinio D, et al. Ganaxolone in children with CDKL5 gene-related epileptic encephalopathy: top-line data from an open-label trial. Poster presentation at the Child Neurology Society 46th Annual Meeting. October 2017.
- Specchio N, Masuoka L, et al. Long-term, durable seizure frequency reduction in children with CDKL5 deficiency disorder (CDD) treated with ganaxolone. Poster presentation at the American Epilepsy Society annual meeting. December 2018.
Background on PCDH19 Related Epilepsy
- Sullivan J, Specchio N, et al. Preliminary evidence of a predictive clinical biomarker in PCDH19-related epilepsy: significant treatment effect of ganaxolone in biomarker-positive patients. Poster presentation at American Epilepsy Society annual meeting. December 2018.
- Tan C, Shard C, Ranieri E, et al. Mutations of protocadherin 19 in female epilepsy (PCDH19-FE) lead to allopregnanolone deficiency. Hum Mol Genet. 2015;24(18):5250-5259. doi:10.1093/hmg/ddv245
- Smith L, Singhal N, El Achkar CM, et al. PCDH19-related epilepsy is associated with a broad neurodevelopmental spectrum. Epilepsia. 2018;59(3):679-689. doi:10.1111/epi.14003
- Lappalainen J, Chez M, Sullivan J, et al. A multi-center, open-label trial of ganaxolone in children with PCDH19 epilepsy. Poster presentation at the American Academy of Neurology 69th Annual Meeting. April 2017.
Ganaxolone in Postpartum Depression
- Maximos B, Riesenberg R. Safety and efficacy of intravenous ganaxolone in severe postpartum depression: results from a double-blind, placebo-controlled phase 2 study. Poster presentation at annual meeting of Society of Biological Psychiatry. 2019.
- Maguire J, Mody I. Steroid hormone fluctuations and GABAAR plasticity. Psychoneuroendocrinology. 2009;34(SUPPL. 1). doi:10.1016/j.psyneuen.2009.06.019
- Evans SEG, Ross LE, Sellers EM, Purdy RH, Romach MK. 3Α-Reduced Neuroactive Steroids and Their Precursors During Pregnancy and the Postpartum Period. Gynecol Endocrinol. 2005;21(5):268-279. doi:10.1080/09513590500361747
Ganaxolone in Fragile X
- Ligsay A, Van Dijck A, Nguyen D V., et al. A randomized double-blind, placebo-controlled trial of ganaxolone in children and adolescents with fragile X syndrome. J Neurodev Disord. 2017;9(1). doi:10.1186/s11689-017-9207-8
Ganaxolone in Status Epilepticus
- Saporito MS, Gruner, JA, et al. Intravenously administered ganaxolone blocks diazepam-resistant lithium-pilocarpine-induced status epilepticus in rats: Comparison with allopregnanolone. J Pharmacology Exp Ther. March 2019. 368: 326-337. Doi:10.1124/jpet.118.252155
- Tsai J, Guptill J, MacLeod D, et al. Phase 1 study to determine the pharmacokinetics, pharmacodynamics, and safety of IV ganaxolone in healthy adults. Poster presentation at the American Epilepsy Society Annual Meeting. December 2018.
- Ramsay RE, Husain AM, et al. Pharmacokinetic and pharmacodynamic (PK/PD) relationship of intravenous ganaxolone in refractory status epilepticus. Poster presentation at the American Epilepsy Society Annual Meeting. December 2019.
- Husain AM, Wu, H et al. Population pharmacokinetic/pharmacodynamic modeling of the electroencephalographic effects of ganaxolone in healthy subjects. Poster presentation at the American Epilepsy Society Annual Meeting. December 2019.
Ganaxolone in Focal Onset Seizures
- Lappalainen J, Tsai J, et al. A multicenter, double-blind, randomized, placebo-controlled phase 3 trial to determine the efficacy and safety of ganaxolone as adjunctive therapy for adults with drug-resistant focal-onset seizures. Poster presentation at the 69th Annual Meeting American Academy of Neurology. 2017.
- Authored by Marinus employees. The pharmacokinetics of two oral ganaxolone formulations under fed and fasted conditions. Poster presentation at the American Society of Epilepsy Annual Meeting. December 2018.