Therapy Reported to Boost Cognition in Phse 2 Clinical Trial
This was in the Alzheimers Research Forum newsletter dated June 3, 2012 (www.alzforum.org
) in the Research News section. Since many LBD patients benefit from Aricept, this type of drug may be helpful also.
1 June 2012. This week, H. Lundbeck A/S, an international pharmaceutical company based in Denmark, announced positive results of a Phase 2 trial. Given along with donepezil, an acetylcholinesterase inhibitor commonly prescribed in Alzheimer's disease (AD), the serotonin/5-hydroxytryptamine receptor antagonist Lu AE58054 provided some added cognitive benefit in patients with moderate AD, according to a company press release. Detailed trial data will be presented this year.
The 5-hydroxytryptamine-6 (5-HT6) receptor is expressed primarily in the central nervous system, especially in learning and memory centers such as the cerebral cortex and hippocampus. Activation of this receptor usually represses cholinergic function (see Bentley et al., 1999), which is important for a range of cognitive functions, including memory and attention. Antagonists of 5-HT6 elevate glutamatergic neurotransmission (see Dawson et al., 2000), which is important for long-term potentiation, learning, and memory. Since Lu AE58054 selectively blocks serotonin from activating 5-HT6 receptors, it may cause an overall enhancement of acetylcholine and glutamate levels.
In the randomized Phase 2 trial, 278 patients in Europe, Canada, and Australia took either Lu AE58054 or placebo in addition to their daily donepezil dose for six months. Compared with patients on donepezil alone, those treated with both drugs improved scores on the Alzheimer's Disease Assessment Scale-cognitive sub-scale (ADAS-cog) and trended positive on measures of Global Status and Activities of Daily Living. The 5-HT6 antagonist was well tolerated, according to the press release. Phase 3 trials are in planning, a company spokesperson said.