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Nuevo tratamiento de la neurotoxicidad asociada a oxaliplatino en los nervios periféricos

Resumen

Tipo:
Oferta Tecnológica
Referencia:
TOCY20160509001
Publicado:
16/05/2016
Caducidad:
16/05/2017
Resumen:
Un instituto de investigación chipriota del campo de neurología y genética ha desarrollado un nuevo enfoque para el tratamiento de la neuropatía inducida por oxaliplatino. La investigación reciente, respaldada por pruebas de laboratorio, ha demostrado que la coadministración de octanol y oxaliplatino bloquea la afectación de los nervios periféricos. El equipo de investigación busca compañías farmacéuticas con el fin de establecer acuerdos de financiación o licencia para continuar con el desarrollo del tratamiento.

Details

Tittle:
Novel treatment of oxaliplatin-induced neurotoxicity in the peripheral nerves.
Summary:
A regional Cypriot research institution in the field of neurology and genetics developed a new approach for treating oxaliplatin-induced neuropathy. Recent in-house research, including extended lab tests, showcased that the co-administration of octanol and oxaliplatin blocks the affectation of the peripheral nerves. The research team is seeking pharmaceutical companies for a financial and/or license agreement to further develop the treatment.
Description:
The research team of a Cypriot research institution developed a novel treatment of the oxaliplatin-induced neurotoxicity in the peripheral nerves. Oxaliplatin is used extensively as a first-line drug in gastrointestinal cancer chemotherapy, in particular metastatic colorectal cancer, although its mechanisms of action remain poorly understood. The major dose-limiting toxicity of oxaliplatin is peripheral neuropathy that can manifest in over 60% of treated patients. The major cause for this oxaliplatin peripheral neuropathy is the hyperexcitability in the peripheral nerve fibres. This effect has been investigated with various methodologies but there was not a conclusive solution to the problem until know. The exact mechanism by which oxaliplatin causes neurotoxicity has remained uncertain, despite extensive previous studies, and currently there is no effective prevention or treatment for this important and frequent dose limiting complication of a common cancer therapy.

In order to study the mechanism cause this oxaliplatin-induced neuropathy, the research team performed ex vivo electrophysiological and histological studies using the isolated sciatic nerve of mouse. When the sciatic nerve preparation was exposed to oxaliplatin, a neurotoxic effect was occurred. This severe oxaliplatin effect was caused by hyperexcitation of individual nerve fibres and is the likely mechanism leading to the acute neuropathy in patients during intravenous application of oxaliplatin.

As a solution, the research team hypothesized a direct functional interplay between gap junction channels and voltage-gated potassium channels (VGKCs) may mediate the oxaliplatin-effect. Specifically, oxaliplatin may cause forced opening, causing accumulation of extracellular K+ generated during axonal activity, which in turn causes indirectly malfunction of VGKCs and prolongation of the repolarising phase. After testing, the team confirmed that octanol compensates for the effect of oxaliplatin by blocking the forced opening of these hemichannels allowing their proper function. Comparing to other gap junction blockers, octanol is safe and has been already used in clinical trials for essential tremor. When these findings were reproduced in vitro, oxaliplatin opens gap junction hemichannels and accordingly this effect was blocked by octanol in a dose dependent manner. Additionally, the morphological examination of the sciatic nerves indicated that initially functional changes in peripheral nerves including hyperexcitability are not accompanied by structural damage of the nerve. Finally, any morphological changes caused by prolonged exposure to oxaliplatin could be prevented by co-administration of octanol. Thus, the research team propose co-administration of octanol as a prevention of oxaliplatin induced acute and chronic neuropathy manifestations.

The research team is seeking for pharmaceutical companies for finance and/or license agreement to further develop the treatment including clinical trials and drug development in order to be available for market distribution.
Advantages and Innovations:
Compared to previous studies, our study provides a novel mechanistic explanation for the observed oxaliplatin neurotoxicity and proposes an effective neuroprotective approach. The use of the gap junction blocker octanol against oxaliplatin-induced neurotoxicity (OIN), as suggested by our findings, overcomes the problems of preventing OIN, since we propose a completely innovative mechanism and show highly effective blockade of the oxaliplatin effect, both functionally and morphologically. Octanol can be readily used in clinical practise as it has a known safety and tolerability profile as previous clinical trials for other disorders showed, and shows the potential for full reversal of the OIN, both at electrophysiological as well as at the morphological level.
Numerous previous attempts to reduce OIN have been reported, using several potential neuroprotective substances. However, none of those agents proved to be effective in preventing OIN. Our study clearly supports the potential for the clinically relevant gap junction blocker octanol to efficiently prevent OIN by blocking Cx32 and Cx29 channels, effectively preventing oxaliplatin effects ex vivo and in vitro.
Stage of Development:
Under development/lab tested
IPs:
Patent(s) applied for but not yet granted
CommeR Statunts Regarding IPR Status:
A PCT application has been filed.

Partner sought

Type and Role of Partner Sought:
Pharmaceutical or other company with expertise in drug development from preclinical to clinical trials stage, that can acquire the license for further exploitation and clinical development of the invention in order to develop a drag for the market.

Client

Type and Size of Client:
R&D Institution
Already Engaged in Trans-National Cooperation:
Si
Languages Spoken:
English
Greek

Keywords

Technology Keywords:
06002007 Ensayos in vitro, experimentos
06001015 Productos farmacéuticos / medicamentos
06002010 Toxicología