ICAD: Investigational Alzheimer's Agent Targets Heavy Metal ...

Tag : Copper Component

Patients treated with 250 mg of clioquinol PBT2, a secondgeneration metal-protein attenuation compound, had a dose-dependentreduction in the 42 amino acid form of amyloid beta incerebrospinal fluid ( P =0.023) compared with placebo, but did not reduce beta amyloid inthe blood, said Lars Lannfelt, M.D., of Uppsala UniversityHospital, and colleagues.
Dr. Lannfelt reported the findings today at a press conference atthe International Conference on Alzheimer's Disease and the resultswere simultaneously published online by Lancet Neurology .
Moreover, patients given the 250-mg dose also showed significantimprovement on two components of the neurospsychological testbattery, but that test "is a relatively new instrument that has notbeen used in many other clinical trials for Alzheimer's disease,"wrote Norman R. Relkin, M.D., of Weill Cornell Medical College inNew York, in a commentary that accompanied the study.
The PBT2 study suggested a novel approach to treating Alzheimer'sdisease. Rather than targeting the accumulation of amyloid plaquein the brain, or tau tangles, it targets the zinc andcopper-mediated toxic oligomerisation of amyloid beta, but does sowithout affecting the availability of zinc and copper ions, whichare essential to brain function.
In the 78-patient study, the drug was well tolerated and there wasno evidence of subacute demyelinating optic neuropathy, which hasbeen reported in studies of earlier clioquinols.
Community dwelling patients, mean age 72, were enrolled from Dec.6, 2006 through Sept. 21, 2007. Twenty patients were randomized to50 mg orally administered PBT2, 29 to 250 mg, and 29 to placebo.Seventy-four patients completed the 12-week study.
The principal outcomes were safety and tolerability, and secondaryoutcomes were plasma and CSF biomarkers and cognition.
Patients in the 250 mg group performed significantly better thanplacebo in two executive function domains of the neuropsychologicaltest battery -- category fluency test ( P =0.041) and trail making part B ( P =0.009).
The 50-mg dose demonstrated no benefit compared with controls.
In his commentary, Dr. Relkin wrote that "clinical response to PBT2is conspicuous by its absence" especially since the drug did reduceamyloid beta concentration in CSF.
In the absence of "biomarker or imaging measures that correlatesignificantly with clinical outcomes, it might be a challenge toprove that the actions of PBT2 are in fact anti-amyloidal."
And, Dr. Relkin added, even if the drug is anti-amyloidal, whetheror not anti-amyloidal therapy would modify the course ofAlzheimer's disease remains a hypothesis that has not been proven.