Research & Drug Development

Voltage-gated sodium channels (VGSC)

VGSC play an important role in the neuronal network by transmitting electrical impulses rapidly throughout cells and cell networks, thereby coordinating higher processes ranging from the transmission of sensory and motor signals to the integration of cognitive processes. Sodium channels are mainly involved in neurological disorders such as chronic pain, epilepsy, schizophrenia and bipolar disorder. At least 11 distinct sodium channels  α-subunits have been identified in mammalian brain and peripheral tissues, and associated to a variety of physiological and pathological events. In particular the sodium channel NAV1.7 is expressed preferentially in most slowly conducting nociceptive neurons and in sympathetic neurons. Gain-of-function mutations in the NAV1.7 channel lead to DRG neuron hyperexcitability associated with severe pain diseases, whereas loss of function mutations lead to indifference to pain. The contribution of NAV1.7 to acquired and inherited pain states and the absence of motor, cognitive and cardiac deficits in patients lacking this channel make it an attractive target for the treatment of neuropathic pain.

Voltage-gated calcium channels (VGCC)

VGCC mediate transient increases in cytoplasmic calcium concentration in response to membrane depolarisation triggering different physiological events such as neuronal excitability, muscle contraction, secretion, neurotransmission, gene expression and gating of other channels. Calcium channels blockers have also been implicated for the treatment of pain and neuroprotection.

Newron Programs

Newron is highly focused in the discovery of medicines that target ion channels for the treatment of neurological disorders, including pain, epilepsy, neurodegenerative and psychiatric disorders. A large body of preclinical and clinical evidence indicates that voltage gated sodium and calcium channels play a crucial role in many disorders of the peripheral and central nervous system due to their importance in regulating neuronal excitability, transmitter release, intracellular metabolism, neurosecretory activity and gene expression.

 Newron, using the latest technologies for pursuing its ion channel drug discovery projects, has already identified a variety of sodium and calcium channel modulators at different stages in preclinical research. In the last few years Newron has built up a strong expertise in this field, with a wide range of pharmacological in vitro assays and in vivo models to select and characterize new candidates.

In the European FP6,  Newron coordinated  a two-year  Cooperative Research Programme (CRAFT) named ION, leading a consortium of small-medium enterprises (SMEs) and academic groups. The funds were raised to speed up drug screening processes  and develop an innovative integrated system for efficient high throughput screening of molecules for ion channel targets related to neurological and psychiatric disorders. As outlined by the SME Unit, European Commission,  The ION project achievements may represent a European solution capable of increasing European competitiveness in this important but highly specialized field (Research *eu magazine, 2009).

Among other internal approaches, Newron is  now  a co-partner in two different  consortia that have been awarded a national grant (Metadistretti, Regione Lombardia) aimed at either  identifying and developing innovative sodium channel Nav 1.7 blockers for the treatment of pain (Navs for pain) and new ion channel modulators for the treatment of pain in women (DOLGEN).

Newron is contributing to these projects with its expertise in sodium channel electrophysiology and pain pharmacology.