MEM 1003
MEM 1003 is a neuronal L-type calcium channel modulator that we are developing for the treatment of Alzheimer’s disease.
MEM 1003 in Alzheimer’s Disease
Patients with Alzheimer’s disease exhibit, among other things, characteristic neuronal imbalances in the second messengers calcium and cAMP. It has been demonstrated that the severity and duration of dementia in Alzheimer’s disease correlates significantly with reduced levels of cAMP. Clinical research indicates that cAMP plays a role in memory, suggesting that drugs directed at this target will have beneficial effects on the treatment of memory loss associated with Alzheimer’s disease. One of the earliest manifestations of Alzheimer’s disease is an impaired regulation of calcium within CNS neurons. Calcium is believed to be an essential mediator of long-term memory formation. While small amounts of calcium are essential for memory formation and other cognitive functions, too much calcium causes a wide variety of toxic symptoms. Neuronal calcium levels are regulated by specific proteins known as L-type calcium channels. Abnormal regulation of these channels is believed to be an early step in the Alzheimer’s disease process, first impairing the pathways required for memory and other cognitive functions and eventually causing the death of neurons.
By blocking L-type calcium channels, MEM 1003 may regulate the flow of calcium. We believe that this approach may enhance cognition by re-establishing normal levels of calcium, which is essential for normal functioning of the neuronal pathways. Further, we believe that this modulation of the calcium flow may impact the progression of the disease by protecting these neurons from further damage caused by the amyloid plaques.
Phase 1 Clinical Trial Program
In July 2003 we completed dose-escalating, double-blind, placebo-controlled Phase 1a and Phase 1b trials with 125 healthy volunteers in the United Kingdom to evaluate the safefty and tolerability profile resulting from single or multiple doses of MEM 1003. Over a dose range of up to 180 milligrams, given twice daily, which was the maximum dose tested, MEM 1003 was generally safe and well tolerated by both young and elderly (over age 55) volunteers.
In addition to safety testing, we assessed cognitive enhancement in 40 of the volunteers from our Phase 1b UK trial. Both young and elderly healthy volunteers were tested using the Cognitive Drug Research battery. In these tests, there were statistically significant positive effects on several of the cognitive measures of longer-term aspects of memory.
In September 2005, we completed a single-center, randomized, double-blind, placebo-controlled Phase 1b safety and tolerability study in patients with Alzheimer’s Disease under a US Investigational New Drug (IND) application.
Phase 2a Clinical Trial - Alzheimer’s disease
In October 2007, we completed a multi-center, randomized, double-blind, placebo-controlled Phase 2a clinical trial of MEM 1003 in patients with mild to moderate Alzheimer’s Disease, We are currently reviewing these results and evaluating the potential for further development of this drug candidate.