Clinical use of an herbal-derived compound (Huperzine A) to treat putative complex partial seizures in a dog

Schneider, Barbara M.; Dodman, Nicholas H.; Faissler, Dominik; Ogata, Niwako

doi:10.1016/j.yebeh.2009.06.011

Cited by 14 publications

(8 citation statements)

References 32 publications

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“…Hup A has been shown to protect against seizures in rat (Tonduli et al, 2001 ), guinea pig (Wang et al, 2013 ), and non-human primate models (Lallement et al, 2002 ) of soman toxicity. In addition, Coleman et al ( 2008 ) reported that Hup A (the [+] isomer) protects against NMDA-induced status epilepticus in rats, and there is one case of Hup-mediated suppression of complex partial seizures in a dog (Schneider et al, 2009 ). Hup A (0.6 mg/kg) was also shown to protect against PTZ-induced seizures in rats (Gersner et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Huperzine A Provides Robust and Sustained Protection against Induced Seizures in Scn1a Mutant Mice

et al. 2016

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De novo loss-of-function mutations in the voltage-gated sodium channel (VGSC) SCN1A (encoding Nav1.1) are the main cause of Dravet syndrome (DS), a catastrophic early-life encephalopathy associated with prolonged and recurrent early-life febrile seizures (FSs), refractory afebrile epilepsy, cognitive and behavioral deficits, and a 15–20% mortality rate. SCN1A mutations also lead to genetic epilepsy with febrile seizures plus (GEFS+), which is an inherited disorder characterized by early-life FSs and the development of a range of adult epilepsy subtypes. Current antiepileptic drugs often fail to protect against the severe seizures and behavioral and cognitive deficits found in patients with SCN1A mutations. To address the need for more efficacious treatments for SCN1A-derived epilepsies, we evaluated the therapeutic potential of Huperzine A, a naturally occurring reversible acetylcholinesterase inhibitor. In CF1 mice, Hup A (0.56 or 1 mg/kg) was found to confer protection against 6 Hz-, pentylenetetrazole (PTZ)-, and maximal electroshock (MES)-induced seizures. Robust protection against 6 Hz-, MES-, and hyperthermia-induced seizures was also achieved following Hup A administration in mouse models of DS (Scn1a+/−) and GEFS+ (Scn1aRH/+). Furthermore, Hup A-mediated seizure protection was sustained during 3 weeks of daily injections in Scn1aRH/+ mutants. Finally, we determined that muscarinic and GABAA receptors play a role in Hup A-mediated seizure protection. These findings indicate that Hup A might provide a novel therapeutic strategy for increasing seizure resistance in DS and GEFS+, and more broadly, in other forms of refractory epilepsy.

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Section: Discussionmentioning

confidence: 99%

Huperzine A Provides Robust and Sustained Protection against Induced Seizures in Scn1a Mutant Mice

et al. 2016

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“…The etiology of this behavior is controversial and has been reported as epileptoid disorders of the visual cortex or simple and complex partial seizures as well as compulsive disorders, hallucinatory behavior, and stereotypy. On the one hand, there are cases reporting FC behavior combined with evident epileptic seizures (e.g., generalized tonic-clinic seizure [GTCS]) [10][11][12]. On the other hand, the literature describes dogs exhibiting FCS, without evident epileptic seizures, with additional behavioral disturbances including licking of the paw and floor, running into objects, lying in the yard and crying, eating mud, following the owner, biting family members without any apparent reason, defecating on the bed [2], or biting and sucking their hindlimbs and pelage [7].…”

Section: Discussionmentioning

confidence: 99%

“…Currently, an epileptic or behavioral nature of FCS is considered to be most likely. Epileptoid disturbances leading to FCS have been reported to include epileptic discharges of the visual cortex, and they may result either from central nervous system (CNS) disease or from idiopathic epilepsy (IE) [3,[8][9][10][11][12][13]. The FCS has also been cited to be a compulsive disorder, hallucinatory behavior, obsessive-compulsive disorder (OCD), stereotypy [1,9,14,15], or dyskinesia as an extrapyramidal disorder [13].…”

Section: Introductionmentioning

confidence: 99%

Retrospective multicenter evaluation of the “fly-catching syndrome” in 24 dogs: EEG, BAER, MRI, CSF findings and response to antiepileptic and antidepressant treatment

Wrzosek

Płonek

Nicpoń

et al. 2015

Epilepsy & Behavior

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The fly-catching syndrome (FCS) is a rare canine condition of sudden, occasional, or constant episodes of biting the air. It may be accompanied by jumping, licking, and swallowing. The etiology of FCS is unknown and controversial. Various explanations for its occurrence have included epileptoid disorders such as visual cortex epileptiform disturbances and simple and complex partial seizures as well as compulsive disorders, hallucinatory behavior, and stereotypy. A retrospective multicenter analysis of 24 dogs with clinical symptoms of FCS is presented. Clinical signs at the time of presentation, the mean age at onset of the disease, the response to treatment, and the clinical outcome were recorded and analyzed in all patients. All dogs underwent clinical, neurological, and otoscopic examinations. Complete blood cell counts (CBCs) and serum chemistry panels were obtained from each dog. Diagnostic testing included MRI and EEG examinations in 21 cases, BAER in 19 cases, and CSF analysis in 20 cases. The EEG revealed spike activity in 8 (38%) of the 21 cases, 7 of which had activity in the occipital lobes. The brainstem auditory evoked response (BAER) revealed three cases of bilateral deafness. The MRI revealed six cases of Chiari malformation (CM), one case of syringohydromyelia (SM), and one case of a falx cerebri meningioma. The dogs were divided into groups according to their treatment protocol. Group A included dogs treated with phenobarbital (PB), and group B consisted of dogs treated with fluoxetine (FLX). Thirty-six percent of the dogs in group A responded to PB, while 100% of the dogs in group B responded to FLX. The results suggest that FCS is more responsive to FLX than PB. However, the etiology of this behavior remains unclear in most cases.

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“…More recently, Huperzine A has demonstrated evidence for preclinical efficacy in animal models of seizure and epilepsy (Bialer et al, 2009;Coleman et al, 2008;Schneider et al, 2009;Tonduli et al, 2001). With approximately 30% of patients with epilepsy resistant to currently available treatments (Brodie and Kwan, 2002), identifying treatments that may be effective for patients with pharmacoresistant epilepsy is heavily demanded by the epilepsy research community (Kelley et al, 2009;Lowenstein, 2011).…”

Section: Predicting Tolerability To Therapies Through Preclinical Evamentioning

confidence: 99%

How Clinical Development Can, and Should, Inform Translational Science

Barker‐Haliski

Friedman²,

White

et al. 2014

Neuron

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There is an urgent need for preclinical translational efforts to be realized as breakthroughs in therapy for the many patients with life-altering conditions affecting the CNS. Despite intensive efforts, few transformative therapies have emerged, and many new potential therapies that looked promising in preclinical development have failed in the clinic. In this Perspective, we suggest that if preclinical scientists partner early with clinical scientists, they can begin to envision the pathway forward for their work through clinical trials. Options might include determining the populations to be treated, issues of dose selection, timing of intervention, duration of intervention, and the availability of biomarkers. In addition, understanding other factors that impact the likelihood that a proof-of-concept trial can be performed, as well as other critical issues, will altogether increase the attractiveness of the project to investors and partners and will also increase the likelihood that the intervention will succeed in the clinic.

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Clinical use of an herbal-derived compound (Huperzine A) to treat putative complex partial seizures in a dog

Cited by 14 publications

References 32 publications

Huperzine A Provides Robust and Sustained Protection against Induced Seizures in Scn1a Mutant Mice

Huperzine A Provides Robust and Sustained Protection against Induced Seizures in Scn1a Mutant Mice

Retrospective multicenter evaluation of the “fly-catching syndrome” in 24 dogs: EEG, BAER, MRI, CSF findings and response to antiepileptic and antidepressant treatment

How Clinical Development Can, and Should, Inform Translational Science

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