Project: Development of a human integrated in vitro Neurotoxicity Safety Platform (NeuroSafe).

In vitro pharmacology profiling of new chemical entities during early phases of drug discovery has recently become an essential tool to predict clinical adverse effects. While different CROs offer high technology platform for cardiac safety testing or more general liability testing, no specific in vitro neurotoxic panels are available. In most of the cases, in fact, in-vivo models are used. However, correlations between animal and human data might be weak in some cases and animal studies are quite expensive, ethically questionable and require large amount of chemical compounds. Therefore we propose to develop an innovative and high throughput platform based on in vitro assays using human targets and cells. The platform will be developed by integrating three complementary highly sensitive and reliable technologies and will include the classes of druggable targets mostly responsible for neuro-toxicity such as inflammation and degeneration: GPCRs, ion channels and neurotransmitter transporters. For the most relevant GPCRs and neurotransmitter transporters, expressed on neurons or glial cells, recombinant assays will be generated in miniaturized format and their functionality will be assessed through FLIPR based technology. While ion channels will be directly analyzed on neuron and glial tissues through a new type of patch clamp approach (PatchServer, patent of NMI in 2011) and Microelectrode array (MEA) recordings. This new human in-vitro platform for neurotoxicity analysis will be of particular relevance for pharmaceutical and agrochemical industries, since it will provide a powerful fast and cost-effective tool for neurotoxicity assessment, applicable to the early phases of drug discovery. This platform can help in flagging and potentially avoiding late, high attrition rates, making finally drug development more cost-effective.

Acronym	NeuroSafe
Network	ETB-PRO
Call	7th call for proposals (Call 2012)

Project partner

Number	Name	Role	Country
	Axxam	Coordinator	Italy
	Germany		Germany