TC-5619 is a novel small molecule that modulates the activity of the alpha7 ( α7) neuronal nicotinic receptor (NNR) subtype. TC-5619 was discovered using Targacept's proprietary drug design technology known as Pentad (TM).
In December 2009, we initiated a Phase 2 clinical proof of concept trial of TC-5619 in cognitive dysfunction in schizophrenia. Pursuant to a mechanism under our collaboration agreement with AstraZeneca initiated by us, AstraZeneca has a future option for an exclusive license to TC-5619 following our completion of the Phase 2 trial.
The α7 NNR is associated with diverse biological functions. A 2003 NIMH consensus meeting (MATRICS/TURNS initiative) identified cognitive deficits as a core feature of schizophrenia that contributes significantly to the lack of functionality of patients1 and the α7 NNR as the most promising target for treatment of such cognitive impairment. Scientific evidence also suggests the α7 NNR is an essential regulator of inflammation arising from injury or infection and plays a key role in protecting neuronal cells from deterioration and death, a process known as neuroprotection.
About Cognitive Dysfunction in Schizophrenia
Schizophrenia is a chronic, severe and disabling form of psychosis. The disease is characterized by symptoms such as delusions, hallucinations, the inability to disregard familiar stimuli (sometimes referred to as sensory gating), disorganized speech, grossly disorganized or catatonic behavior and prolonged loss of emotion, feeling, volition or drive. In addition, schizophrenia is often marked by impairment in cognitive functions, such as attention, vigilance, memory and reasoning that play a primary role in the inability of schizophrenic patients to function normally. It has been estimated that up to 75% of schizophrenic patients experience cognitive dysfunction.
Traditional treatments for schizophrenia are not effective to treat cognitive dysfunction in schizophrenia. While it has been reported that more recently developed treatments for schizophrenia, known as "atypical anti-psychotics," may have some effect on cognitive dysfunction, the effect may not be lasting or lead to an improvement in daily activities. There are currently no drugs approved in the United States or Europe specifically for cognitive dysfunction in schizophrenia.
1 Fenton WS, Stover EL, Insel TR: Breaking the log-jam in treatment development for cognition in schizophrenia: NIMH perspective. Psychopharmacology (2003) 169: 365-366.