A Phase 2a, single-blind, placebo-controlled safety and efficacy study of two doses of NRP2945 in patients showing drug-resistant typical absence epilepsy as a form of their genetic, generalized epilepsy pattern
A Double-blind, Randomised, Placebo-controlled Study to Determine the Safety, Pharmacokinetics and Maximum Tolerated Dose of NRP2945 In Healthy Adult Volunteers.
100 项与 NRP-2945 相关的临床结果
100 项与 NRP-2945 相关的专利（医药）
项与 NRP-2945 相关的文献（医药）
2021-03-30·European journal of pharmacology3区 · 医学
Anti-epileptogenic effect of NRP2945 in the pilocarpine model of temporal lobe epilepsy.
3区 · 医学
作者: Francesca Lovisari ; Annunziata Guarino ; Marie Soukupova ; Chiara Falcicchia ; Selene Ingusci ; Pietro Marino ; Mark Thomas ; Frank Sieg ; Michele Simonato
Innovative therapeutic strategies are highly needed to tackle the major medical needs of epilepsy, like prevention of epilepsy development in at-risk individuals, treatment of severe and drug-resistant forms, control of co-morbidities. The Neural Regeneration Peptide NRP2945 (a peptidomimetic analogue of the human CAPS-2 protein) has been recently found to exert many potentially anti-epileptic effects, for example increased neuronal survival and differentiation. In the present study, we tested the effects of NRP2945 on the development of epilepsy (epileptogenesis) and on chronic, spontaneous seizures, by using the pilocarpine model of temporal lobe epilepsy. We found that NRP2945 exerts a robust anti-epileptogenic effect, reducing the frequency of spontaneous seizures, exerting a significant neuroprotective effect and attenuating anxiety-like behaviors and cognitive impairment. These effects appear to depend on modulation of the epileptogenesis process and not on seizure suppression, because NRP2945 did not reduce frequency or duration of spontaneous seizures when administered to already epileptic animals. These findings may form the basis for a preventive therapy for individuals at-risk of developing epilepsy.
2017-07-01·Neurochemical Research3区 · 医学
Disease-Modifying Effects of Neural Regeneration Peptide 2945 in the GAERS Model of Absence Epilepsy
3区 · 医学
作者: Dezsi, Gabi ; Sieg, Frank ; Thomas, Mark ; O'Brien, Terence J. ; van der Hart, Marieke ; Jones, Nigel C.
Epilepsy is a common neurological condition characterised by spontaneous recurrent seizures. Current anti-epileptic drugs are only effective and tolerated in ~70% of patients, leaving a substantial proportion of patients untreated. As such, there is a pressing need to develop new therapies. We assessed the anti-seizure activity of Neural Regeneration Peptide 2945 (NRP 2945) in the GAERS model of absence epilepsy. Drug effects on seizures were assessed using two study designs. Male adult GAERS were implanted with EEG electrodes to measure seizure frequency. The first study compared the effects of acute sc injection of vehicle, NRP 10 µg/kg, NRP 20 µg/kg, and controlled against the active comparator Valproaic acid (200 mg/kg). In the second study, animals received one of four treatments for 4 weeks: vehicle, NRP 60 µg/kg/day, NRP 120 µg/kg/day (delivered by continuous infusion) or NRP 20 µg/kg sc injected every second day (e.s.d). In the acute study, we found significant (p < 0.01) anti-seizure effects in animals treated with NRP2945 (20 µg/kg) and VPA, with NRP2945 slightly more efficacious, despite the 70,000 times lower molar dosage. In the chronic study, animals receiving 120 µg/kg/day and NRP 20 µg/kg e.s.d had significantly fewer seizures (p < 0.001), compared with vehicle. These effects were sustained for at least 10 days after drug treatment had ceased, indicative of disease-modifying activity. We demonstrate sustained anti-seizure effects of NRP2945, a potent small molecule peptide which enters the brain and is devoid of adverse effects. Early stage first-in-man trials have been initiated for subcutaneously delivered NRP2945 which is a promising step to providing therapeutic benefits for refractory epilepsy patients.
2015-02-01·Neuropeptides (Oxford, United Kingdom)3区 · 医学
Anticonvulsant effect of neural regeneration peptide 2945 on pentylenetetrazol-induced seizures in rats
3区 · 医学
作者: Sajadian, Azadeh ; Esteghamat, Sana ; Karimzadeh, Fariba ; Eshaghabadi, Arezou ; Sieg, Frank ; Speckmann, Erwin-Josef ; Meuth, Sven ; Seidenbecher, Thomas ; Budde, Thomas ; Gorji, Ali
Neuron regeneration peptides (NRPs) are small synthetic peptides that stimulate neural proliferation, migration, and differentiation with no apparent toxicity and high target specificity in CNS. The aim of this study was to investigate the effect of NRP2945 on seizure activity induced by pentylenetetrazol (PTZ) in rats. Using behavioural assessment and electrocorticographical recordings, the effects of different doses of NRP2945 (5-20 µg/kg) were tested on seizure attacks induced by PTZ injection. In addition, the effect of NRP2945 was evaluated on the production of dark neurons and expression of GABAA receptor α and β subunits and GAD-65 in the hippocampus and somatosensory cortex of the rat brain. Intraperitoneal injection of NRP2945 at 20 µg/kg prevented seizure attacks after PTZ injection. NRP2945 at doses of 5 and 10 µg/kg significantly decreased the total duration of seizure attacks and reduced the amplitude, duration and latency of epileptiform burst discharges induced by PTZ. In addition, the peptide significantly inhibited the production of dark neurons in the hippocampus and somatosensory cortex of epileptic rats. NRP2945 also significantly increased the expression of GABAA receptor α and β subunits and GAD-65 in the hippocampus and somatosensory cortex compared with PTZ treated rats. This study indicates that NRP2945 is able to prevent the seizure attacks and neuronal injuries induced by PTZ, likely by stimulating GABAA and GAD-65 protein expression and/or protecting these components of GABAergic signalling from PTZ-induced alteration. Further studies are needed to elucidate the potential role of NRP2945 as an antiepileptic drug.