Prana's PBT2 Improved Cognition in 12 Week Trial
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In just 12 weeks of clinical trials, PBT2 significantly increased dementia patients' cognitive performance.
In further news, the Australian government announced its intent to commit $15 million to the Mental Health Research Institute (MHRI) as crucial funding toward the commencement of a large scale trial of PBT2.
PBT2 is made by Prana Biotechnology. MHRI is their long standing partner in PBT2 research for the treatment of
- Alzheimer’s disease
- Huntington’s disease.
Clinical Trial Starts with Alzheimer's
The grant would go towards the further development of PBT2 by Prana, including a clinical trial involving 525 patients with mild to moderate Alzheimer’s, treated for twelve months. The study is aimed to confirm the results received in an earlier trial. The company is also seeking further funding for the trial. PBT2 has already demonstrated very promising results in an earlier Phase IIa trial, which in just 12 weeks showed significant improvement in cognitive tests that measure executive function in Alzheimer’s patients.
Exciting Huntington's Results
In collaboration with the University of California San Francisco, PBT2 was tested in a type of laboratory mouse genetically altered to mimic Huntington's in fast-motion. These mice are called the R6/2 transgenic model of Huntington’s Disease. The mice exhibited significant improvement in coordination, motor function and life span. The average cumulative life span of the PBT2 treated animals was around 40% longer than that of the untreated controls. Significantly, examination of the brains of treated mice showed marked reduction in atrophy of the striatal tissue. In Huntington’s, this tissue degenerates, resulting in the loss of brain volume, a hallmark of the disease.
Experts Are Impressed
- Rudolph E. Tanzi, Ph.D., the Joseph P. and Rose F. Kennedy Professor of Neurology, at Harvard Medical School said: “The combined preclinical and clinical data on PBT2 leads me to believe that PBT2 has the best chance of all currently available potential competitors to be the first effective disease modifying treatment for Alzheimer’s Disease. The Victorian Premier deserves congratulations for pledging this funding”.
- Sam Gandy, M.D Ph.D, Mount Sinai School of Medicine, New York, described a recent report on PBT2 as “providing a major advance in deciphering the underlying causes of Alzheimer’s Disease while at the same time pointing us toward a new and exciting strategy for treating or preventing the disease with a drug such as PBT2, which affects brain metals”.
- Sir Gustav Nossal, a world renowned research biologist and former winner of the Albert Einstein World Award for Science, described Prana’s PBT2 research as “one of the iconic discoveries in Australian medical and health research”.
How It Works
PBT2 works on three metals in the brain:
- Zinc
- Copper
- Iron
Copper & Zinc: In a recent presentation at ICAD, Prana's Head of Research, Associate Professor Robert Cherny, showed that the effectiveness of PBT2 lies in a unique combination of complementary activities. PBT2 acts to detoxify A-beta by disarming it of copper and zinc and returns these crucial metals to neurons. Dr. Cherny showed that by returning these metals to neurons, important cell signaling pathways are activated that prevent neuronal death and promote neuronal function. In addition, data was also presented linking the neuroprotective qualities of PBT2 with beneficial effects evident in an animal model of Huntington’s Disease.
Iron Overload: In additional research, evidence published in Cell shows that the source of beta-amyloid, the beta- amyloid precursor protein (APP), plays a hitherto unknown critical role in exporting iron out of neurons. If APP fails to carry out this role, iron builds up in the neurons contributing to oxidative stress, neurofibrillary tangle formation and ultimately neuronal cell death. Importantly, Prana scientists demonstrated that synaptic zinc can prevent APP from performing its normal iron transporting role. Synaptic zinc levels and distribution changes in the Alzheimer’s brain, because zinc released into the synaptic space is drawn into the beta-amyloid that forms plaques in the synapse. This is problematic for the brain because neurons are deprived of the zinc required for neurotransmission and the zinc induces toxic beta-amyloid oligomer formation. Moreover, as now indicated by the research in the journal, Cell, the zinc caught up in the beta-amyloid can be transported or exchanged to the APP, impeding its ability to prevent iron buildup in neurons.
Accordingly, the maintenance of correct zinc levels in the brain is vital for neuronal function and ultimately cognition.
Prana’s PBT2 acts as a zinc chaperone that transports zinc from the brain beta-amyloid deposits and returns it to neurons to facilitate normal neurotransmission. PBT2 has also demonstrated important neuroprotective and neurotrophic properties, consistent with its ability to prevent zinc from impairing the ability of APP to prevent iron overload.
Conclusions from Recent Data
Mr. Geoffrey Kempler, Executive Chairman of Prana, said of the research published in Cell, “The report is the most comprehensive validation to date of the importance of brain metals, which are the key therapeutic target of PBT2, in treating Alzheimer’s Disease. These new findings strengthen the expectation that PBT2 will reverse brain damage in Alzheimer’s Disease, and raise hopes that it will achieve further success in the next stage of clinical trials”.
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More Information
Click here to listen to an audio webcast on Prana's plans to advance Alzheimers clinical trial.
Source:
- Iron-Export Ferroxidase Activity of β-Amyloid Precursor Protein Is Inhibited by Zinc in Alzheimer's Disease, Cell, Volume 142, Issue 6, 857-867, 02 September 2010
- Prana Biotechnology Limited
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