Schizophrenia Daily News Blog

Memory Pharmaceuticals to Initiate Medication Trial for Cognitive Impairment Associated with Schizophrenia

USA-based Memory Pharmaceuticals has announced plans for a Phase IIa proof-of-concept study of a new medication temporarily designated "MEM 3454", a nicotinic alpha-7 partial agonist, in the treatment of cognitive impairment associated with schizophrenia (CIAS). The firm added that it plans to initiate the trial in the fourth quarter of this year.

Memory explained that it had taken several steps to ensure full support for the program, including the expansion of its development accord with Swiss drugmaker Roche.

In a recent conference call, Memory Pharmaceuticals executives had this to say about this medication program:

At the moment, there are no specific treatments for cognitive deficits associated with schizophrenia and current therapies for schizophrenia have very little impact on these cognitive symptoms.

It is well known that a large percentage of [people who suffer from schizophrenia] abuse nicotine in the form of smoking cigarettes. While it is unclear why this is the case, it has been suggested that smoking is a form of self-medication with nicotine.

The underlying theory is that nicotine alters the function of some of these neurotransmitters implicated in schizophrenia, such as dopamine, glutamate, [GAVA] and acetylcholine.

Nicotine increases the release of these neurotransmitters, especially dopamine and acetylcholine, which helps improve cognitive function.

Of course, the obvious downside of this is that nicotine is addictive and chronic nicotine administration leads to desensitization or inactivation of the nicotine receptors. Also obviously, smoking brings with it other well documented side effects.

This has led to the search for nicotinic alpha-7 agonists, such as MEM 3454, that provide the benefits of nicotinic receptor stimulation without the problems associated with smoking and nicotine.

With the stage set, let's talk about MEM 3454 and why we believe it has potential utility in CIAS.

MEM 3454 has been tested in multiple animal models of cognition and has shown significant positive effects.

At the multiple ascending dose portion of the Phase I program at a 15 mg dose administered once daily for a period of 13 days, MEM 3454 had a statistically significant effect at a P value of 0.007 on the quality of episodic secondary memory score from the CDR battery.

QESM is a composite score derived from memory tests in the CDR battery that measure the efficiency with which study participants are able to remember words and pictures.

Importantly, in pre-clinical studies MEM 3454 was found to reverse sensory and auditory gating deficits in young rats and the administration of MEM 3454 in a micro-dialysis experiment also produced a strong and prolonged release of dopamine and acetylcholine in the regions of the brain that are believed to be important for the treatment of CIAS.

In a 2904 survey of 46 cognitive neuroscientists and neuropharmacologists conducted in connection with the National Institutes of Health Initiative known as Measurement and Treatment Research to Improve Cognition in Schizophrenia, or MATRICS, nicotinic alpha-7 receptor agonists were selected as one of the most interesting targets in the development of treatments for cognitive deficits in schizophrenia, particularly in the areas of attention and vigilance.

Our pre-clinical and clinical results, coupled with the scientific community's enthusiasm and interest in this target and the wealth of research on the potential utility of a nicotinic alpha-7 agonist as a treatment of CIAS are the key drivers behind our enthusiasm for this drug candidate as a potential therapy for CIAS.

Memory has also amended its loan agreement with investment firm Hercules Technology Growth Capital, securing an extra $5.0 million to fund the proposed trial.

Also in support of the trial, Memory has agreed to sell stock worth up to $6.0 million to investors, principally to the Chevy Chase, Maryland-headquartered Stanley Medical Research Institute.