Product
BGC20-1259
Indication
Alzheimer’s disease/dementia
Phase
Phase I
Description
BGC20-1259 is a multifunctional compound for the treatment of Alzheimer’s Disease (AD), other age related dementias and elderly depression with cognitive impairment. It combines inhibition of acetylcholinesterase and serotonin transport with L-type Ca-channel blocking activity to improve cognitive and behavioural symptoms of the disease. Based on its neuroprotective properties, BGC20-1259 also has the potential slow disease progression in AD patients.
Further Information
BGC20-1259 has shown an excellent clinical profile in Phase I studies, a single ascending dose study in healthy young males and a repeat ascending dose study in healthy young males and healthy young and elderly males and females. The pharmacokinetic profile over the efficacious dose range [as assessed by positron emission tomography (PET) study, and based on extrapolation from preclinical data] shows linearity and low inter-subject variability, and there were no differences observed between males and females and between young and elderly. In addition, BGC20-1259 was very well tolerated exhibiting minimal peripheral cholinomimetic side -ffects, which is likely due to the opposing mechanisms related to the mixed activity of this compound. Pharmacodynamic endpoints indicated dose-dependent inhibition of acetylcholinesterase (AChEI) and increases in cognitive performance and self-rated calmness in young and elderly volunteers. The compound is currently being progressed towards a Phase IIa proof of concept study in AD.
AD is the most prevalent and one of the most devastating of the neurodegenerative disorders. AD has a complex aetiology and pathophysiology, and there are multiple presentations with varying symptoms and course of illness. It is characterised by a loss of a number of neurotransmitter systems, particularly cholinergic and serotoninergic neurons. As well as the core symptom of memory loss, patients may suffer depressive symptoms, behavioural disturbances and sleep disorders. Current AChEI symptomatic treatments for AD address the cognitive impairment associated with the disease, but based on the single target approach (AChEI) have little effect on other symptoms of the disease. Based on preclinical data, including a recent PET study, BGC20-1259 shows high occupancy at both SERT and AChE receptors at doses which exhibit minimal side-effects and also inhibits L-type Ca channels in a use-dependent manner. This multi-targeted approach has the potential to offer distinct advantages over currently marketed treatments. In addition, by combining all properties within one molecule, BGC20-1259 has the potential to simplify dosing in Alzheimer’s patients.
While disease modifying drugs are currently the focus of significant development effort, symptomatic treatment is likely to be used in combination with any new disease modifying drug that comes to market. As BGC20-1259 should provide improved symptomatic relief from AD, it could be highly suitable for combining with disease modifying agents.
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