Wolfgang Löscher
Translational Epilepsy Research · Chief Scientific Officer at PrevEp Inc.
Professor Wolfgang Löscher is one of the world's leading epilepsy researchers, ranked #1 in epilepsy by ScholarGPS (2025) among over 30 million scholars worldwide. With more than 800 peer-reviewed publications and an h-index of 121, his translational research has transformed epilepsy treatment — most notably through his discovery of the unique antiseizure properties of levetiracetam (Keppra), which became the first blockbuster drug in epilepsy therapy.
Current Roles
- Head, Translational Neuropharmacology Lab — NIFE, Department of Experimental Otology, Hannover Medical School (2023–Present)
- Emeritus Professor — Dept. Pharmacology, Toxicology & Pharmacy, University of Veterinary Medicine Hannover (2019–Present)
- Co-founder & Chief Scientific Officer — PrevEp Inc., Bethesda, MD, USA (2018–Present)
Explore
Research
Over 50 years of translational research bridging basic neuroscience and clinical epilepsy treatment
Publications
Selected publications from over 800 peer-reviewed papers in epilepsy and neuropharmacology
Curriculum Vitae
A career spanning over five decades in epilepsy research, from Berlin to Hannover to the world
Curriculum Vitae
A career spanning over five decades in epilepsy research and neuropharmacology
Wolfgang Löscher is Head of the Translational Neuropharmacology Lab, NIFE, Department of Experimental Otology of the ENT Clinics, Hannover Medical School, Germany, and Professor and former Chair of the Department of Pharmacology, Toxicology & Pharmacy, University of Veterinary Medicine Hannover, Germany. He graduated in Veterinary Medicine from the Free University of Berlin, with postgraduate training in Pharmacology, particularly Neuropharmacology, and Toxicology, as well as in Neurochemistry in Germany, Denmark, and the United States.
Following posts in both industry and academia, he was the Director of the Department of Pharmacology in Hannover, Germany, from 1987–2022, as well as the Head of the interdisciplinary Center for Systems Neuroscience in Hannover. In 2023, he became Head of the Translational Neuropharmacology Lab, NIFE, of the Hannover Medical School.
He has made fundamental contributions to the development of new antiseizure medications, including the discovery of the unique antiseizure profile of levetiracetam, which was the foundation of the clinical development of this globally most commonly used antiseizure medication. He has contributed to the understanding of numerous other antiseizure medications, including gabapentin, vigabatrin, retigabine (ezogabine), abecarnil, and imepitoin (the first therapy developed for canine epilepsy).
He has spearheaded fundamental advances in animal models of seizures and epilepsy, in the pharmacology of antiseizure medications, in the mechanisms of drug resistance in epilepsy, and in the pathophysiology of acquired epilepsies to find new targets for preventive treatment. Throughout, he has collaborated closely with major pharmaceutical companies to foster the development of new antiseizure medications.
He has been a founding and managing editor of the journal Epilepsy Research and serves on the editorial board of six scientific journals, including the Annals of Neurology and Epilepsia.
He has over 800 refereed publications and an h-index of 121. His awards include the Epilepsy Research Award for Outstanding Contributions to the Pharmacology of Antiepileptic Drugs of the International League against Epilepsy (ILAE) in 2001, the American Epilepsy Society's Epilepsy Research Award for Basic Science Research in 2006, the Ambassador for Epilepsy Award of the ILAE and IBE in 2011, the European Epileptology Award of the ILAE/CEA in 2014, and the Lifetime Accelerator Award of the Epilepsy Foundation of America in 2018.
In 2000, he was elected to the German National Academy of Sciences Leopoldina, the oldest continuously existing academy of natural sciences and medicine in the world. In 2025, he was honored as a Highly Ranked Scholar by ScholarGPS (Los Angeles, CA, USA) and, based on his achievements of the prior 5 years, received rank 1 of 50,871 ranked scholars in the field of epilepsy.
Since 2015, Löscher has served as an external consultant for the Epilepsy Therapy Screening Program (ETSP) of the NIH/NINDS in the US. In 2018, Löscher co-founded the US-based startup PrevEp, Inc. (Bethesda, MD). He is currently CSO of this company, which has the major goal of developing new therapies for preventing post-traumatic epilepsy after traumatic brain injury.
Research
Over 50 years of translational research bridging basic neuroscience and clinical epilepsy treatment
Main Research Areas and Key Contributions
Epilepsy Prevention (Antiepileptogenesis)
Developing strategies to prevent the development of epilepsy after brain insults such as traumatic brain injury, stroke, or status epilepticus. This research aims to identify and validate treatments that can be administered after a brain insult to prevent the subsequent development of spontaneous seizures. Over the last ~10 years, Löscher's group developed rationally chosen cocktails of drugs that target epileptogenesis by different mechanisms and demonstrated the potential of such cocktails to prevent epilepsy in different rodent models. Currently, one of these cocktails is being translated to the clinical arena.
Drug Resistance in Epilepsy
Investigating the mechanisms underlying pharmacoresistance in epilepsy, a major clinical problem affecting approximately one-third of epilepsy patients. Research includes the role of drug efflux transporters at the blood-brain barrier and intrinsic disease mechanisms that limit drug efficacy. Furthermore, Löscher's group developed the first rodent models of drug-resistant epilepsy. In a proof-of-concept study, it was shown that selective inhibition of the efflux transporter P-glycoprotein counteracts pharmacoresistance in epileptic rats. Subsequently, Löscher was involved in clinical studies to translate these findings to patients.
Novel Antiseizure Medication Development
Translational research on the pharmacology of existing and novel antiseizure medications. In cooperation with UCB Pharma, this work led to the identification of levetiracetam's unique antiseizure properties — it became the first blockbuster drug in epilepsy therapy (marketed as Keppra). In cooperation with Boehringer Ingelheim, Löscher was involved in the development of imepitoin, the first therapy specifically developed for canine epilepsy. Furthermore, by cooperating with the pharmaceutical industry, Löscher was involved in the preclinical development of various other novel antiseizure medications, including vigabatrin, retigabine (ezogabine), abecarnil, and gabapentin, and various drugs that did not reach the epilepsy market.
Novel Strategies for Preventing the Adverse Outcome of Neonatal Seizures
In cooperation with Prof. Kai Kaila in Helsinki, Löscher's group established a rat model of asphyxia-induced neonatal seizures and characterized the pharmacology of this model and its later-in-life adverse outcome. When studying rats over about 50% of their lifetime, adverse consequences for neurodevelopment were similar to those observed in infants, including neuroinflammation, neuronal damage, cognitive decline, behavioral alterations, and epilepsy. Subsequently, it was evaluated whether the adverse outcome can be altered by treatments administered after asphyxia, resulting in the surprising finding that the benzodiazepine midazolam almost completely prevents the long-term consequences of asphyxia and neonatal seizures.
The Role of GABA in the Pathophysiology and Pharmacology of Epilepsy
Starting in the mid-1970s, Löscher defined how the antiseizure drug valproate influences the synthesis and metabolism of the inhibitory neurotransmitter GABA, clarifying one of the key mechanisms by which this drug exerts anticonvulsant effects. Later, Löscher demonstrated that valproate and gabapentin enhance the GABA turnover in specific brain regions such as the substantia nigra pars reticulata, and that levetiracetam reduces the spontaneous firing of GABAergic neurons in this region. Valproate's effect on GABA metabolism was also demonstrated in humans, using CSF and plasma GABA analysis. Later, he was involved in the development of novel drugs that act by inhibiting GABA aminotransferase (e.g., vigabatrin), GABA uptake, or that work as partial and/or subtype-specific positive allosteric modulators (PAMs) at GABAA receptors (e.g., abecarnil and imepitoin). Furthermore, he studied the role of GABA in the piriform cortex for the pathophysiology and pharmacology of epilepsy. Based on Löscher's findings on the piriform cortex, he proposed to include resection of this area during epilepsy surgery. This was recently shown to increase the efficacy of resective surgery in patients with drug-resistant focal epilepsy.
Funding
Löscher's research has been funded by the German Research Foundation, the US National Institutes of Health, the European Union's EURIPDES and EPITARGET programs, and the Epilepsy Foundation of America.
Current Lab
Translational Neuropharmacology Lab
NIFE, Department of Experimental Otology of the ENT Clinics
Hannover Medical School, Germany
The lab focuses on new pharmacological treatments for neonatal seizures and their later-in-life consequences, including hearing loss.
Publications
A selection from over 800 peer-reviewed publications in epilepsy research, pharmacology, and neuroscience
Selected Original Reports
Safety and efficacy of eslicarbazepine acetate for seizure prevention in patients with stroke at high risk of developing post-stroke epilepsy
Lancet Neurol., 25, 256–267, 2026
First clinical trial to study whether eslicarbazepine acetate prevents or reduces the incidence of epilepsy after acute ischemic stroke or acute intracerebral hemorrhage
Intranasal Seletracetam in a Patient with Reading Epilepsy: First-in-Human Use to Prevent Reflex Seizures
Ann. Neurol., 99, 535–539, 2026
First-in-human proof of concept that intranasal seletracetam prevents reflex seizures
Ranking of antiseizure medications in a panel of focal seizure models predicts their comparative efficacy in clinical add-on trials in drug-resistant focal epilepsy
Epilepsia, in press, 2026
A new approach for predicting antiseizure efficacy in clinical trials
Midazolam Prevents the Adverse Outcome of Neonatal Asphyxia
Ann. Neurol., 93, 226–243, 2023
Surprising finding that midazolam prevents the later-in-life adverse outcome of neonatal asphyxia in a rat model
Systematic evaluation of rationally chosen multitargeted drug combinations: a combination of low doses of levetiracetam, atorvastatin and ceftriaxone exerts antiepileptogenic effects in a mouse model of acquired epilepsy
Neurobiol. Dis., 149, 105227, 2021
Discovery of a highly effective antiepileptogenic drug cocktail
Proof-of-concept that network pharmacology is effective to modify development of acquired temporal lobe epilepsy
Neurobiol. Dis., 134, 104664, 2020
First description that a cocktail of multi-targeted drugs prevents epilepsy
The circadian dynamics of the hippocampal transcriptome and proteome is altered in experimental temporal lobe epilepsy
Science Adv., 6, eaat5979, 2020
The hippocampus operates in a different functioning mode in epilepsy
Association of Piriform Cortex Resection with Surgical Outcomes in Patients with Temporal Lobe Epilepsy
JAMA Neurol., 76, 690–700, 2019
These results support the importance of resecting the piriform cortex in neurosurgical treatment of temporal lobe epilepsy and suggest that this area has a key role in seizure generation
Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood
Nature Microbiol., 3, 1161–1174, 2018
Description of an important sex difference in the consequences of Zika virus infection
A novel mechanism of drug extrusion by brain endothelial cells via lysosomal drug trapping and disposal by neutrophils
PNAS, 115, E9590–E9599, 2018
These findings introduce a novel mechanism that might contribute to brain protection against potentially toxic xenobiotics, including therapeutically important chemotherapeutic drugs
Chemokine receptors CCR2 and CX3CR1 regulate viral encephalitis-induced hippocampal damage but not seizures
PNAS, 115, E8929–E8938, 2018
CNS inflammatory mechanism(s) other than the infiltrating myeloid cells trigger the development of seizures during viral encephalitis
Gene therapy decreases seizures in a model of incontinentia pigmenti
Ann. Neurol., 82, 93–104, 2017
The study provides evidence for the therapeutic benefit of a brain endothelial-targeted gene therapy in incontinentia pigmenti
Single dose efficacy evaluation of two partial benzodiazepine receptor agonists in photosensitive epilepsy patients
Epilepsy Res., 122, 30–36, 2016
First clinical trial showing that the partial GABAA receptor agonist abecarnil exerts antiseizure efficacy
Isoflurane prevents acquired epilepsy in rat models of temporal lobe epilepsy
Ann. Neurol., 80, 896–908, 2016
First description that isoflurane is antiepileptogenic
A novel prodrug-based strategy to increase effects of bumetanide in epilepsy
Ann. Neurol., 75, 550–562, 2014
The study shows that the goal of designing bumetanide prodrugs that specifically target the brain is feasible
Converging PET and fMRI evidence for a common area involved in human focal epilepsies
Neurology, 77, 904–910, 2011
An area of the human primary olfactory cortex may be an attractive new target for epilepsy therapy, including neurosurgery, electrical stimulation, and focal drug delivery
A novel positron emission tomography imaging protocol identifies seizure-induced regional overactivity of P-glycoprotein at the blood-brain barrier
J. Neurosci., 31, 8803–8811, 2011
Development of a PET protocol for studying overexpression of P-glycoprotein at the blood-brain barrier of epileptic rats
The anticonvulsant response to valproate in kindled rats is correlated with its effect on neuronal firing in the substantia nigra pars reticulata: a new mechanism of pharmacoresistance
J. Neurosci., 31, 16423–16434, 2011
Description of a new mechanism of drug resistance
Disease-modifying effects of phenobarbital and the NKCC1 inhibitor bumetanide in the pilocarpine model of temporal lobe epilepsy
J. Neurosci., 30, 8602–8612, 2010
A combination of phenobarbital and bumetanide, but neither drug alone, is disease-modifying in a model of focal epilepsy
Neurogenesis in the adult rat piriform cortex
Neuroreport, 17, 571–574, 2006
First description that neurogenesis occurs in the adult piriform cortex
The multidrug transporter hypothesis of drug resistance in epilepsy: proof-of-principle in a rat model of temporal lobe epilepsy
Neurobiol. Dis., 24, 202–211, 2006
First description that inhibition of the efflux drug transporter P-glycoprotein reverses drug resistance in epileptic rats
Multidrug resistance in epilepsy: rats with drug-resistant seizures exhibit enhanced brain expression of P-glycoprotein compared with rats with drug-responsive seizures
Brain, 128, 1358–1368, 2005
First description that the efflux drug transporter P-glycoprotein is increased in rats with pharmacoresistant focal epilepsy
Anticonvulsant efficacy of the low-affinity partial benzodiazepine receptor agonist ELB 138 in a dog seizure model and in epileptic dogs with spontaneously recurrent seizures
Epilepsia, 45, 1228–1239, 2004
First description that the novel partial GABA receptor agonist imepitoin exerts antiseizure effects in epileptic dogs
Functional inactivation of a fraction of excitatory synapses in mice deficient for the active zone protein bassoon
Neuron, 37, 787–800, 2003
Bassoon is not essential for synapse formation, but plays an essential role in the regulated neurotransmitter release from a subset of glutamatergic synapses
N-methyl-D-aspartate receptor blockade after status epilepticus protects against limbic brain damage but not against epilepsy in the kainate model of temporal lobe epilepsy
Neuroscience, 118, 727–740, 2003
First study on the chicken-or-egg causality dilemma of hippocampal sclerosis and epilepsy, indicating that these two phenomena are not causally related
Deficit of striatal parvalbumin-reactive GABAergic interneurons and decreased basal ganglia output in a genetic rodent model of idiopathic paroxysmal dystonia
J. Neurosci., 20, 7052–7058, 2000
Striatal GABAergic neurons are involved in paroxysmal dystonia
Seizure suppression in kindling epilepsy by grafts of fetal GABAergic neurons in rat substantia nigra
J. Neurosci. Res., 51, 196–209, 1998
First successful demonstration that neurotransplantation of fetal GABAergic neurons is anticonvulsant
Amygdala-kindling induces a lasting reduction of GABA-immunoreactive neurons in a discrete area of the ipsilateral piriform cortex
Synapse, 29, 299–309, 1998
GABAergic neurons in the piriform cortex are involved in epileptogenesis
A comparison of the effects of valproate and its major active metabolite E-2-en-valproate on single unit activity of substantia nigra pars reticulata neurons in rats
J. Pharmacol. Exp. Ther., 277, 1305–1314, 1996
Valproate and its main active metabolite decrease firing of neurons in the substantia nigra pars reticulata
Immunocytochemical localization of GABA immunoreactivity in dentate granule cells of normal and kindled rats
Neurosci. Lett., 212, 41–44, 1996
The first description that glutamatergic dentate granule cells also produce GABA
Susceptibility of different cell layers of the anterior and posterior part of the piriform cortex to electrical stimulation and kindling
Neuroscience, 66, 265–276, 1995
Characterization of the role of the piriform cortex in temporal lobe epilepsy
Profile of ucb L059, a novel anticonvulsant drug, in models of partial and generalized epilepsy in mice and rats
Eur. J. Pharmacol., 232, 147–158, 1993
Description of the unique antiseizure profile of levetiracetam
Plasma GABA and seizure control with vigabatrin
Lancet, 341, 117, 1993
Increases in plasma GABA are correlated with the individual response to vigabatrin
Kindling as a model of drug-resistant epilepsy: Selection of phenytoin-resistant and nonresistant rats
J. Pharmacol. Exp. Ther., 258, 483–489, 1991
The first description of the phenytoin-resistant kindled rat
Responses to NMDA receptor antagonists altered by epileptogenesis
Trends Pharmacol. Sci., 12, 52, 1991
The first description that kindling-induced epileptic brain changes strikingly increase the adverse effect potential of competitive NMDA receptor antagonists
Anticonvulsant and proconvulsant effects of inhibitors of GABA degradation in the amygdala-kindling model
Eur. J. Pharmacol., 163, 1–14, 1989
The anticonvulsant effect of vigabatrin correlates with GABA increases in brain nerve endings
Intermittent flumazenil and benzodiazepine tolerance: discouraging findings in rats
Lancet, i, 1386–1387, 1989
The findings indicate that tolerance and physical dependence are distinct properties of benzodiazepines
Is amygdala kindling in rats a model for drug-resistant partial epilepsy?
Exp. Neurol., 93, 211–226, 1986
Description of the first rodent model of pharmacoresistant focal epilepsy
Valproic acid increases γ-aminobutyric acid in CSF of epileptic children
Lancet, ii, 225, 1984
The first clinical demonstration that valproate increases GABA
GABA in plasma and cerebrospinal fluid of different species. Effects of γ-acetylenic GABA, γ-vinyl GABA and sodium valproate
J. Neurochem., 32, 1587–1591, 1979
The first preclinical demonstration that valproate increases GABA in CSF and plasma
Effect of convulsant and anticonvulsant agents on level and metabolism of γ-aminobutyric acid in mouse brain
Naunyn-Schmiedeberg's Arch. Pharmacol., 296, 263–269, 1977
The first demonstration that valproate counteracts the decrease in GABA synthesis after convulsants
Speaking Engagements
Invited lectures, keynote addresses, and conference presentations
Each year, W. Löscher presents invited lectures or keynote addresses at major conferences or academic seminars in Europe and the US
Recent Examples
Seizure freedom and mechanisms of antiseizure medications
Congress of the German Society for Clinical Neurophysiology and Functional Imaging
Seletracetam revisited: A missed opportunity for epilepsy therapy
Cleveland Clinic, Epilepsy Grand Rounds
New strategies for prevention of epilepsy
Epilepsy Clinic (SEIN) Utrecht, The Netherlands
New approaches for the treatment of neonatal seizures
15th European Epilepsy Congress, Rome, Italy
How lamotrigine and topiramate affected epilepsy treatment and the development of new ASMs since their approval 30 years ago
15th European Epilepsy Congress, Rome, Italy
Mechanistic targets for PTE prevention
IC-PTE, Milan, Italy
Mammalian models of status epilepticus — their value and limitations
9th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures, London, UK
Consultancies
Industry collaborations and advisory roles in epilepsy drug development
Contact
Get in touch for research collaborations, speaking invitations, or consultancy inquiries
Institutional Address
Translational Neuropharmacology Lab
NIFE, Department of Experimental Otology
ENT Clinics, Hannover Medical School
Stadtfelddamm 34, 30625 Hannover, Germany
Loescher.Wolfgang@mh-hannover.de
For research collaborations, speaking invitations, and general inquiries