Epilepsy, Neurosteroids, Translational Pharmacology and New Drug Development
Pharmacological and translational research in epilepsy, neurosteroids and new drug development for brain disorders, especially mechanism-based therapies for epilepsy, status epilepticus, epileptogenesis, brain injury and chemical neurotoxicity. Development of investigational new drugs, pharmaceuticals and novel CNS drug products.
Reddy’s major research goals are to understand the molecular pathophysiology and develop novel therapeutic strategies for epilepsy, with an emphasis on neurosteroids and GABA inhibition in the brain. Neurosteroids are steroids synthesized locally within the brain that rapidly change neural excitability by non-genomic mechanisms, principally via postsynaptic GABAA receptors that play critical role in epilepsy. Current work in his lab is focused on uncovering molecular mechanisms of neurosteroids in epilepsy and brain disorders, and testing the efficacy of mechanism-based, rationale therapeutic strategies for epilepsy and epileptogenesis. Reddy lab is utilizing multidisciplinary approaches such as pharmacological, molecular, electrophysiological (patch-clamp), mass spectrometry, and transgenic mouse models in research projects.
Epilepsy and seizure disorders affect about 3 million people in the United States and 50 million people worldwide. Despite the availability of several antiepileptic drugs, about one-third of people with epilepsy show seizures that do not respond to even the best available treatment. Presently, there is no cure for epilepsy. Reddy’s lab is testing the efficacy of novel drugs and subunit-preferring agents for treatment or prevention of seizure disorders such as catamenial epilepsy, temporal lobe epilepsy, and status epilepticus. Catamenial epilepsy is a menstrual cycle-related seizure disorder characterized by an increase in seizures around menstruation. Because progesterone plays a vital role in women with epilepsy, his lab is uncovering the molecular mechanism of progesterone actions in the brain. He is developing pathology-based models for validating ‘neurosteroid replacement therapy’, a new strategy that he introduced for catamenial epilepsy. Status epilepticus is a neurological emergency characterized by a prolonged, continuous seizure activity with significant mortality and morbidity. Novel therapies are desperately needed for rapid and effective treatment of status epilepticus. Reddy’s lab is translating recent findings into therapy development using mechanism-based strategy that promote tonic inhibition in complex brain disorders such as epilepsy, brain injury and chemical neurotoxicity.
He is a faculty member in TAMU Institute of Neuroscience, Texas Brain & Spine Institute, and TAMU graduate program.
- Carver CM, Wu X, Gangisetty O and Reddy DS (2014). Perimenstrual regulation of extrasynaptic delta-containing GABA-A receptors mediated tonic inhibition and neurosteroid sensitivity. Journal of Neuroscience 34(43):14181-97.
- Reddy DS. Role of hormones and neurosteroids in epileptogenesis. Frontiers in Cellular Neuroscience 2013, 7(115): 1-20.
- Reddy DS (2014). Neurosteroids and their role in sex-specific epilepsies. Neurobiology of Disease 72(Pt B):198-209.
- Carver CM and Reddy DS. Neurosteroid interactions with synaptic and extrasynaptic GABA-A receptors: Regulation of subunit plasticity, phasic and tonic inhibition, and neuronal network excitability. Psychopharmacology 2013, 230(2):151-188.
- Wu X, Gangisetty O, Carver CM and Reddy DS. Estrous cycle-regulation of extrasynaptic δ-containing GABA-A receptor-mediated tonic inhibition and limbic epileptogenesis. J Pharmacol Exp Therap 2013, 346:146-160.
- Reddy DS and Kuruba R. Experimental models of status epilepticus and neuronal injury for evaluation of therapeutic interventions. International Journal of Molecular Sciences 2013, 14:18284-18318.
- Reddy DS. The pathophysiological and pharmacological basis of current drug treatment of migraine headache. Expert Reviews of Clinical Pharmacology 2013, 6(3):271-288.
- Reddy DS. Neuroendocrine aspects of catamenial epilepsy. Hormones & Behavior 2013, 63: 254–266.
- Reddy DS and Ramanathan G. Finasteride inhibits the disease-modifying activity of progesterone in the hippocampus kindling model of epileptogenesis. Epilepsy & Behavior 2012, 25:92-97.
- Reddy DS. Novel new drug approvals in 2011: A succinct analysis of drug discovery trends in the United States. Int J Pharm Sci Nanotech. 2012, 5: 1661-1665.
- Reddy DS, Gould J, and Gangisetty O. A mouse kindling model of perimenstrual catamenial epilepsy. J Pharmacol Exp Therap 2012, 341:784-793.
- Reddy DS. Current drug shortages in the United States. Pharma Times 2012, 44 (6):22-25.
- Reddy DS. Role of anticonvulsant and antiepileptogenic neurosteroids in the pathophysiology and treatment of epilepsy. Frontiers in Neuroendocrinology 2011 (vol 2); article 38, pp 1-11.
- Reddy DS (author). Pharmacy Quiz. 2nd Edition. PBS Publishers, Hyderabad 2012, pages 1-1150. **Major review book for pharmacy graduate and board exams**
- Wu X and Reddy DS. Integrins as receptor targets for neurological disorders. Pharmacology & Therapeutics 2012, 134:68-81.
- Reddy DS and Mohan A. Development and persistence of limbic epileptogenesis are impaired in mice lacking progesterone receptors. Journal of Neuroscience 2011;31 650-658.
- Reddy DS, Gangisetty O. and Briyal S. Disease-modifying activity of progesterone in the hipocampus kindling model of epileptogenesis. Neuropharmacology 2010, 59:573-581.
- Reddy DS. Neurosteroids: Endogenous role in the human brain and therapeutic potentials. Progress in Brain Research 2010, 186: 113-137.
- Gangisetty O. and Reddy DS. Neurosteroid withdrawal regulates GABA-A receptor α4-subunit expression and seizure susceptibility by activation of PR-independent Egr3 pathway. Neuroscience 2010, 170: 865-880.
- Reddy DS and Jian K. The testosterone-derived neurosteroid androstanediol is a positive allosteric modulator of GABA-A receptors. J Pharmacol Exp Therap 2010, 334:1031-1041.
- Reddy DS and Rogawski MA. Ganaxolone suppression of behavioral and electrographic seizures in the mouse amygdala kindling model. Epilepsy Research 2010, 89:254-260.
- Reddy DS. Clinical pharmacokinetic interactions between antiepileptic drugs and hormonal contraceptives. Expert Rev Clin Pharmacol 2010, 3(2):183-192.
- Reddy DS. The role of neurosteroids in the pathophysiology and treatment of catamenial epilepsy. Epilepsy Research 2009, 85 (1): 1-30.
- Gangisetty O and Reddy DS. The optimization of TaqMan real-time RT-PCR assay for transcriptional profiling of GABA-A receptor subunit plasticity. Journal of Neuroscience Methods 2009, 181(1):58-66.
- Reddy DS and Rogawski MA. Neurosteroid replacement therapy for catamenial epilepsy. Neurotherapeutics 2009, 6(2):392-401.
- Reddy DS. Mass spectrometric quantification and physiological-pharmacological activity of androgenic neurosteroids. Neurochemistry International 2008; 52(4-5):541-553.
- Reddy DS and Zeng YC. Effect of neurosteroid withdrawal on spontaneous recurrent seizures in a rat model of catamenial epilepsy. FASEB Journal 2007, 21(6): A1179-A1180.
- Rao MV, Hattiangady B, Reddy DS, and Shetty AK. Hippocampal neurodegeneration, spontaneous seizures and mossy fiber sprouting in F344 rat model of temporal lobe epilepsy. Journal of Neuroscience Research 2006, 83(6):1088-105.
- Reddy DS. Physiological role of adrenal deoxycorticosterone-derived neuroactive steroids in stress-sensitive conditions. Neuroscience 2006, 138:911-920.
- Reddy DS, O’Malley BW, and Rogawski MA. Anxiolytic activity of progesterone in progesterone receptor knockout mice. Neuropharmacology 2005, 48:14-24.
- Reddy DS, Chien B, and Ramu K. A high-performance liquid chromatography-tandem mass spectrometry assay of the androgenic neurosteroid 3a-androstanediol in plasma. Steroids 2005, 70:879-885.
- Reddy DS, Castenada DA, O’Malley BW, and Rogawski MA. Antiseizure activity of progesterone and neurosteroids in progesterone receptor knockout mice. The Journal of Pharmacology and Experimental Therapeutics 2004, 310: 230-239.
- Reddy DS and Woodward R. Ganaxolone: a prospective overview. Drugs of the Future 2004, 29:227-242.
- Reddy DS. Is there a physiological role for the neurosteroid THDOC in stress-sensitive conditions? Trends in Pharmacological Sciences 2003, 24: 103-106.