NEW YORK (Reuters Health) - Treatment with the experimental metal-protein attenuating compound PBT2 is a safe and tolerable means of improving executive function in patients with Alzheimer's disease, new research suggests.
Executive function refers to a set of mental processes used to plan, organize, focus attention and manage time. Defects in executive function are strongly associated with attention deficit and learning disabilities. Individuals with poor executive function also have trouble with memory.
Researchers found that PBT2 altered disease biomarkers, molecules that coincide with the present of disease, in cerebrospinal fluid, but not in plasma. This supports the idea that a central mechanism of action is involved in amyloid-beta metabolism, the researchers report in an online issue of The Lancet, Neurology.
They explain that amyloid-beta is a protein in the body that forms amyloid plaques in the brain, a key feature of Alzheimer's disease. The new PBT2 compound targets the chemical processes of zinc and copper, the metal ions involved in amyloid-beta formation, and thus indirectly prevents the biogenesis of amyloid-beta.
Based on strong laboratory evidence and other convincing research, Dr. Craig W. Ritchie and colleagues from the PBT2-201-EURO study group conducted a phase IIa study of PBT2 that included 78 patients with early-stage Alzheimer's disease. All of the patients were taking a stable dose of an acetylcholinesterase inhibitor drug to preserve the brain's neuroreceptors..
The subjects were randomly assigned to receive PBT2 at a daily dose of 50 or 250 mg or to receive placebo. Although the researchers examined biomarker and cognition endpoints, the main focus was on the safety and tolerability of PBT2, according to the report.
Over half of the patients experienced at least one treatment-related event, but only four patients dropped out of the study, Ritchie, from Imperial College London, and colleagues note. Overall, 50 percent of patients treated with the lower dose of PBT2 and 62 percent given the higher dose experienced a side effect compared with 48 percent of placebo patients. None of the events in the active treatment groups were severe.
