eltoprazine (DU 28853) / Amarantus BioSci, PsychoGenics, ReqMed - LARVOL DELTA

Activation of the 5-HT1A Receptor by Eltoprazine Restores Mitochondrial and Motor Deficits in a Drosophila Model of Fragile X Syndrome. (PubMed, Int J Mol Sci) - "Using the Drosophila model of FXS, we demonstrated that treatment with eltoprazine, a 5-HT1A agonist, can ameliorate synaptic transmission, correct mitochondrial deficits, and ultimately improve motor behavior. While these findings suggest that the 5-HT1A-mitochondrial axis may be a promising therapeutic target, further investigation is needed in the context of FXS."

Journal • CNS Disorders • Developmental Disorders • Fragile X Syndrome • Genetic Disorders • Mental Retardation • Metabolic Disorders • Psychiatry

Eltoprazine modulated gamma oscillations on ameliorating L-dopa-induced dyskinesia in rats. (PubMed, CNS Neurosci Ther) - "Excessive cortical gamma oscillation is a compelling clinical indicator of dyskinesia. The detection of enhanced PAC and functional connectivity of gamma-band oscillation can be used to guide and optimize deep brain stimulation parameters. Eltoprazine has potential clinical application for dyskinesia."

Journal • Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease

Levodopa-induced dyskinesia: a brief review of the ongoing clinical trials. (PubMed, Neurodegener Dis Manag) - No abstract available

Clinical • Journal • Review • CNS Disorders • Movement Disorders • Parkinson's Disease

Neuroinflammation and L-dopa-induced abnormal involuntary movements in 6-hydroxydopamine-lesioned rat model of Parkinson's disease are counteracted by combined administration of a 5-HT receptor agonist and A receptor antagonist. (PubMed, Neuropharmacology) - "Finally, tyrosine hydroxylase and dopamine transporter examined to evaluate neurodegeneration, showed a significant equal decrease in all experimental groups. The present findings suggest that combination of l-dopa with eltoprazine and preladenant may be promising therapeutic strategy for delaying the onset of dyskinesia, preserving l-dopa efficacy and reducing neuroinflammation markers in nigrostriatal system of 6-OHDA-lesioned rats."

Journal • Preclinical • CNS Disorders • Immunology • Inflammation • Movement Disorders • Oncology • Parkinson's Disease • GFAP • IL10 • IL1B • TNFA

Amarantus receives Notice of Allowance for U.S. Patent Application covering method of treating Parkinson's diseaselevodopa-induced dyskinesia (PD-LID) (PRNewswire) - "Amarantus BioScience ...announced that it has received a Notice of Allowance from the U.S. Patent and Trademark Office (USPTO) covering the use of combination 5HT1A and 5HT1B agonists, including eltoprazine, for the treatment of PD-LID. The USPTO issues a Notice of Allowance after it makes a determination that a patent should be issued based on examination of the filing. In the case of eltoprazine, AMBS' lead clinical stage product, the Notice will provide additional intellectual property protection through 2027."

Patent • Parkinson's Disease

Amarantus Subsidiary Elto Pharma receives notice of allowance for European patent application covering method of treating cognitive impairment associated with Alzheimer's disease and Parkinson's disease with eltoprazine (GlobeNewswire) - "Amarantus Bioscience...today announced that its wholly-owned subsidiary Elto Pharma, Inc. has received an Intent to Grant a Patent notice from the European Patent Office (EPO) for Eltoprazine. The notice refers to the patent application 'Treatment for Neurological and Mental Disorders,' and covers the method of treating cognitive impairment or dysfunction associated with Parkinson's disease, Alzheimer's disease, Mild Cognitive Impairment, dementia, or certain other neurological disorders with Eltoprazine. Once issued, the patent will extend Elto Pharma's intellectual property exclusivity for Eltoprazine in Europe into 2029."

Patent • CNS Disorders • Parkinson's Disease

Amarantus subsidiary Elto Pharma receives notice of allowance for european patent application covering method of treating cognitive impairment associated with Alzheimer's disease and Parkinson's disease with eltoprazine (GlobeNewswire) - "Once issued, the patent will extend Elto Pharma's intellectual property exclusivity for Eltoprazine in Europe into 2029. Elto Pharma is currently redesigning its Phase 2b clinical study for Eltoprazine in the treatment of Levodopa-induced dyskinesia (PD-LID), targeted to begin enrollment in 2018. Eltoprazine has received Orphan Drug Designation from the US FDA for Eltoprazine in the treatment of PD-LID."

Orphan drug • Patent • Trial status • CNS Disorders • Epilepsy

Amarantus subsidiary Elto pharma announces the issuance of patents in Singapore and New Zealand covering treatment of Parkinson’s LID (GlobeNewswire) - "Amarantus Bioscience Holdings, Inc...announced...Elto Pharma, Inc. was granted patents in Singapore and New Zealand covering the therapeutic use of Eltoprazine for the treatment of motor symptoms associated with Parkinson’s disease therapies....Both patents are titled 'Treatment of Motor Symptoms and Movement Disorder Side Effects Associated with Parkinson’s disease treatments' and are valid into 2033."

Patent • CNS Disorders • Parkinson's Disease

Amarantus announces presentation of eltoprazine phase 1/2a clinical data at the 19th International Congress of Parkinson's disease and movement disorders (CNN Money) - "Amarantus BioScience Holdings...announced that data from the Phase 1/2a clinical study of eltoprazine for the treatment of Parkinson's disease levodopa-induced dyskinesia (PD-LID) has been accepted for presentation at the 19th International Congress of Parkinson's Disease and Movement Disorders being held June 14-18, 2015, in San Diego, CA. Amarantus previously announced that it will commence a multi-center, 60-subject Phase 2b study in individuals with PD-LID before the end of the June 2015. The Company expects to report top-line results from this Phase 2b study in the second quarter of 2016."

Anticipated new P2b trial • Anticipated P1/2 data • Anticipated P2b data • Parkinson's Disease

Investigational drugs in Phase I and Phase II for Levodopa-Induced dyskinesia. (PubMed) - "Interesting results have been obtained, for example, with partial 5-HT1A/5-HT1B receptor agonist eltoprazine and mGluR5 negative allosteric modulator dipraglurant. Confirmation of these results through large-scale, phase III clinical trials will be needed, to obtain new pharmacological tools that may be used to optimize the treatment of PD patients with motor complications."

Journal • Biosimilar • CNS Disorders • Gene Therapies • Parkinson's Disease

Eltoprazine prevents levodopa-induced dyskinesias by reducing causal interactions for theta oscillations in the dorsolateral striatum and substantia nigra pars reticulate. (PubMed, Neuropharmacology) - "4) Chronic eltoprazine reduced BG theta activity in LID rats and normalized information flow directionality, relative to that in LID rats not given eltoprazine. These results indicate that dStr activity plays a determinative role in the causal interactions of theta oscillations and that serotonergic inhibition may suppress dyskinesia by reducing dStr-SNr theta activity and restoring theta network information flow."

Journal

Technological prospection: Patents mapping involving compounds for the treatment of L-DOPA-induced dyskinesias. (PubMed, Expert Opin Ther Pat) - "Thus, the present study aimed to prospect patents of alternative treatment strategies for L-DOPA-induced dyskinesias.Areas covered: This review covers the therapeutic patents published over the 2001-2019 period in the WIPO, INPI, and ESPACENET, which report treatment strategies for L-DOPA induced dyskinesias (LIDs).Expert opinion: In recent years, several pharmaceutical companies, as well as universities and researchers have tested effective compounds for LIDs treatment, showing substances that act on central pathways as antagonists and agonists of the serotonergic system, which may result in the key to onset of LIDs in animal models of PD. Future works aiming to elucidate the L-DOPA, Flibanserin, Eltoprazine, and Pridopidina mechanisms of action on the receptors of the serotonergic system and D receptors of the indirect pathway, will allow the development of effective therapies for LIDs."

Journal

Amarantus subsidiary Elto Pharma receives notice of allowance covering use of eltoprazine combined with CBD to treat Parkinson’s disease (GlobeNewswire, Amarantus Bioscience Holdings, Inc.) - “Amarantus Bioscience Holdings, Inc…today announced that subsidiary Elto Pharma, Inc. has received a notice of allowance from the European Patent Office (EPO) covering the use of eltoprazine and eltoprazine in combination with a number of chemical compounds, including cannabidiol (CBD) in the treatment of Parkinson’s disease and Parkinson’s disease levodopa-induced dyskinesia (PD-LID). Once issued, the patent will protect the use of eltoprazine in the treatment of Parkinson’s and PD-LID through 2034....Amarantus has entered into a binding term sheet for Elto Pharma to license eltoprazine to Emerald Organic Products. The transaction is expected to close in the fourth quarter of 2019."

Licensing / partnership • Patent

Amarantus provides recapitalization update to shareholders (GlobeNewswire) - "Importantly, going forward Emerald will be assuming the costs of developing the eltoprazine, Engineered Skin Substitute, MANF and PhenoGuard programs...Phase 2 Agitation in Alzheimer’s. Next Step: Range Finding Studies."

New trial

Amarantus Enters Into Agreement to License Diverse Therapeutics Portfolio to CBD-focused Emerald Organic Products (GlobeNewswire, Amarantus Bioscience Holdings, Inc.) - "Amarantus will receive Emerald Preferred Stock to be valued at a minimum of $100M in 2022, and up to double digit royalties (in addition to passthrough royalties and milestones) in exchange for worldwide, exclusive development and commercial rights to eltoprazine, engineered skin substitute (ESS), mesencephalic astrocyte-derived neurotrophic factor (MANF) and PhenoGuard."

Commercial

Neuroinflammation and activation of Zif-268 in dyskinetic 6-OHDA-lesioned rats is counteracted by association of a 5-HT1A/1B receptor agonist and an A2A receptor antagonist (MDS Congress 2019) - "The present findings suggest that combined administration of L-dopa with eltoprazine and preladenant may be a promising therapeutic strategy for treating motor symptoms, delaying the onset of dyskinesia and reducing the neuroinflammation response in PD."

Preclinical