By Ed Susman
CHICAGO -- July 30, 2008 -- The experimental drug PBT2 -- a metal-protein-attenuating compound -- appears safe and shows signs of efficacy in patients with mild Alzheimer's disease, according to results of a phase 2 study.
Study researchers said that PBT2, which interrupts the detrimental impact of reactions between copper and zinc and beta amyloid demonstrated a dose-dependent reduction in the 42 amino acid form of beta amyloid -- the most toxic form of amyloid that is believed to be a causative agent in development of Alzheimer's disease.
"These results indicate that PBT2 is having an impact in the underlying biology of Alzheimer's disease, which is very exciting," said Jeffrey Cummings, MD, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California. "This is critical proof of concept, and the safety and efficacy demonstrated by PBT2 in this study warrant evaluation in larger-scale clinical trials."
Patients treated with PBT2 250 mg daily had a reduction of beta-amyloid in cerebrospinal fluid compared with placebo (P = .023) but not in the blood, said Dr. Cummings in a press briefing here on July 29 at the 2008 International Conference on Alzheimer's Disease (ICAD).
The paper was made available simultaneously online in The Lancet Neurology (Lannfelt L et al. In press).
Patients who received the 250-mg dose also showed significant improvement on 2 components of the neuropsychological test battery, but that test "is a relatively new instrument that has not been used in many other clinical trials for Alzheimer's disease," wrote Norman R. Relkin, MD, Weill Medical College of Cornell University, New York, New York, in a commentary that accompanied the online report.
Dr. Cummings said that the success of PBT2 suggests a novel approach to treating Alzheimer's disease. Instead of targeting the accumulation of amyloid plaque in the brain or tau tangles, it targets the zinc- and copper-mediated toxic oligomerisation of beta amyloid but manages to do so without affecting the availability of zinc and copper ions, which are essential to brain function.
For their 12-week study, Dr. Cummings and colleagues recruited 78 patients with a mild form of Alzheimer's disease and assigned 29 to receive placebo, 20 patients to the 50-mg dose of PBT2, and 29 to the 250-mg dose of the drug. PBT2 was delivered in oral capsules.
The PBT2 50-mg dose failed to distinguish itself from placebo. However, Dr. Cummings said that the 250-mg dose achieved a significant reduction in beta-42 amyloid in the cerebrospinal fluid when compared with placebo (P = .006). Patients on the 250-mg dose of PBT2 also demonstrated improvements in the Trail Making Test Part B (P = .0009) and the Category Fluency Test (P = .041) when compared with the placebo group.
The study was wholly funded by Prana Biotechnology.
[Presentation title: Targeting A-Beta as a Modifying Therapy of Alzheimer's Disease: Safety, Efficacy and Biomarker Findings of a Phase 2a Randomised, Double-Blind Placebo-Controlled Trial of PBT2. Abstract HT-01-04]
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