Delving into the Latest Updates on NRP-2945 with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

NNZ 4945, NNZ-4945, NRP 2945

Target

CXCR4

Mechanism

CXCR4 modulators(C-X-C motif chemokine receptor 4 modulators)

Therapeutic Areas

Nervous System DiseasesCongenital DisordersOther Diseases

Active Indication

EpilepsyEpilepsy, Temporal LobeLennox Gastaut Syndrome

Inactive Indication

Amyotrophic Lateral SclerosisAngelman SyndromeEpilepsy, Absence+ [2]

Originator Organization

Neuren Pharmaceuticals Ltd.

Active Organization

Neuren Pharmaceuticals Ltd.

CuroNZ Ltd.

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

Structure

Molecular FormulaC41H75N21O11

InChIKeyNSVUYPMUSKVTRT-FRSCJGFNSA-N

CAS Registry1145786-97-5

Gene Sequence

Sequence Code 9880459

The inhibitory neurotransmitter γ-aminobutyric acid (GABA) plays an important role in the modulation of neuronal excitability, and a disruption of GABAergic transmission contributes to the pathogenesis of some seizure disorders. Although many currently available antiseizure medications do act at least in part by potentiating GABAergic transmission, there is an opportunity for further research aimed at developing more innovative GABA-targeting therapies. The present article summarises available evidence on a number of such treatments in clinical development. These can be broadly divided into three groups. The first group consists of positive allosteric modulators of GABA_A receptors and includes Staccato^® alprazolam (an already marketed benzodiazepine being repurposed in epilepsy as a potential rescue inhalation treatment for prolonged and repetitive seizures), the α2/3/5 subtype-selective agents darigabat and ENX-101, and the orally active neurosteroids ETX155 and LPCN 2101. A second group comprises two drugs already marketed for non-neurological indications, which could be repurposed as treatments for seizure disorders. These include bumetanide, a diuretic agent that has undergone clinical trials in phenobarbital-resistant neonatal seizures and for which the rationale for further development in this indication is under debate, and ivermectin, an antiparasitic drug currently investigated in a randomised double-blind trial in focal epilepsy. The last group comprises a series of highly innovative therapies, namely GABAergic interneurons (NRTX-001) delivered via stereotactic cerebral implantation as a treatment for mesial temporal lobe epilepsy, an antisense oligonucleotide (STK-001) aimed at upregulating NaV1.1 currents and restoring the function of GABAergic interneurons, currently tested in a trial in patients with Dravet syndrome, and an adenoviral vector-based gene therapy (ETX-101) scheduled for investigation in Dravet syndrome. Another agent, a subcutaneously administered neuroactive peptide (NRP2945) that reportedly upregulates the expression of GABA_A receptor α and β subunits is being investigated, with Lennox-Gastaut syndrome and other epilepsies as proposed indications. The diversity of the current pipeline underscores a strong interest in the GABA system as a target for new treatment development in epilepsy. To date, limited clinical data are available for these investigational treatments and further studies are required to assess their potential value in addressing unmet needs in epilepsy management.

01 Jun 2021·European journal of pharmacologyQ3 · MEDICINE

Anti-epileptogenic effect of NRP2945 in the pilocarpine model of temporal lobe epilepsy

Q3 · MEDICINE

Article

Author: Guarino, Annunziata ; Simonato, Michele ; Thomas, Mark ; Sieg, Frank ; Marino, Pietro ; Lovisari, Francesca ; Falcicchia, Chiara ; Ingusci, Selene ; Soukupova, Marie

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.

01 Jul 2017·Neurochemical researchQ3 · MEDICINE

Disease-Modifying Effects of Neural Regeneration Peptide 2945 in the GAERS Model of Absence Epilepsy

Q3 · MEDICINE

Article

Author: van der Hart, Marieke ; Sieg, Frank ; Jones, Nigel C ; Dezsi, Gabi ; Thomas, Mark ; O'Brien, Terence J

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.

100 Deals associated with NRP-2945

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Epilepsy, Absence	Phase 2	AU	CuroNZ Ltd.	11 Dec 2018
Epilepsy	Phase 2	-	Neuren Pharmaceuticals Ltd.	-
Epilepsy, Temporal Lobe	Phase 2	-	CuroNZ Ltd.	-
Lennox Gastaut Syndrome	Phase 2	-	CuroNZ Ltd.	-
Amyotrophic Lateral Sclerosis	Phase 1	NZ	CuroNZ Ltd.	07 Mar 2020
Angelman Syndrome	Preclinical	NZ	CuroNZ Ltd.	17 Apr 2020
Rett Syndrome	Preclinical	NZ	CuroNZ Ltd.	17 Mar 2020
Multiple Sclerosis	Preclinical	NZ	CuroNZ Ltd.	-