23 March 2011
Prana says new data shows the ability of its lead drug PBT2 to repair damage in an Alzheimer’s affected brain, facilitating the restoration of cognition in Alzheimer’s disease.
Prana said the findings by researchers at the University of Melbourne and Victoria’s Mental Health Research Institute led by the MHRI’s Dr Paul Adlard help explain the rapid improvement in cognition previously reported in transgenic Alzheimer's mice and in patients in a phase IIa clinical trial with PBT2.
The article, published in the Public Library of Sciences’ journal Plos One, is entitled ‘Metal Ionophore Treatment Restores Dendritic Spine Density and Synaptic Protein Levels in a Mouse Model of Alzheimer’s Disease’ and an abstract is available at: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0017669.
The abstract concluded that the data suggested “that PBT2 may affect multiple aspects of synaptic health [and] efficacy”.
“In Alzheimer's disease therefore, PBT2 may restore the uptake of physiological metal ions trapped within extracellular beta-amyloid aggregates that then induce biochemical and anatomical changes to improve cognitive function,” the abstract said.
Prana said the article described the biochemical and anatomical changes occurring in the brains of transgenic Alzheimer's mice treated with PBT2.
The company said that after 11 days of treatment, the brains of the Alzheimer’s mice showed a statistically significant increase in the numbers of spines on the branches or dendrites of neurons in the hippocampus, compared to controls.
Prana said the hippocampus was a memory centre affected in Alzheimer’s disease.
The company said that increasing the number of spines was important as it permitted more neurons to interconnect with any particular neuron thereby increasing the brain’s capacity to carry out learning and memory functions.
Prana said the anatomical changes to the hippocampus were also accompanied by increased levels in key proteins involved in learning, memory and neuronal growth, with the levels of many of the proteins restored to levels seen in healthy, cognitively normal animals.
Prana’s head of research Prof Robert Cherny said the ability of PBT2 to promote the forming and reforming of connections between neurons was “fundamental to the repair of brain tissue damaged by [Alzheimer’s disease] and the expression of key neuronal receptors and signaling proteins indicates that the repaired tissue is functional”.
The company said that in a series of parallel experiments, the authors also administered PBT2 to cultured neurons and in these in vitro experiments, PBT2 was able to elicit elongation of arm-like projections from the immature developing neurons called neuritis, which could mature into either axons or dendrites of an adult neuron.
Prana said it was significant that the changes observed in the in vitro experiments were strictly dependent on the presence of copper or zinc in the growth medium, confirming that the restorative effect of PBT2 was due to its ability to deliver these metals to deficient neurons and it had previously been shown that PBT2 neutralised the toxicity of the Alzheimer's amyloid beta protein by preventing the formation of toxic aggregates or oligomers.
Prana said the data further explained how PBT2 could achieve rapid improvements in cognition by liberating copper and zinc trapped in amyloid deposits and returning those essential metals to neurons, where they are needed for normal function.
“These findings further demonstrate the unique combination of detoxification and neuronal restoration provided by PBT2 that underlie cognitive improvement in the clinic,” Dr Cherny said.
Prana was up 2.5 cents or 17.9 percent to 16.5 cents.