PBT2 Dementia Trial is 2012 Editor's Choice
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PBT2 experienced significant strides in 2011. It is the Alzheimer's & Dementia Weekly Editor's Choice. PBT2 is arguably the dementia drug in clinical trials to make the most progress in 2011 and offer the greatest hope for 2012.
Research
The Journal of Biological Chemistry published a study offering powerful validation of PBT2 as a treatment for a number of neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntingtons diseases.
The study's team leader was Professor Susan Lindquist, a Professor of Biology at Massachusetts Institute of Technology.
The study first explored the general therapeutic potential of 8-hydroxyquinolines (8-OHQ) in treating these disorders, then went into further depth to explore specific types, such as PBT2.
The drugs were protective against the neurotoxic proteins behind these neurodegenerative diseases. Specifically, PBT2 was sited as providing positive therapeutic results.
PBT2 is Prana Biotechnology's lead drug for treating dementia in Alzheimer's and Huntington's disease. It is a specific type of 8-OHQ. Prana designed and selected PBT2 therapy for its enhanced efficacy and tolerability.
The study is accessible under the title, "Different 8-OHQ's Protect Models of TDP-43, alpha-synuclein, and Polyglutamine Proteotoxicity through Distinct Mechanisms".
200,000 compunds were tested in this study. From all these compounds, the researchers identifiied 8-OHQ compounds as protective against neurodegeneration. The mechanism they identified was their influence on metal homeostasis in the brain.
In other words, PBT2 works by keeping brain metals in balance. It mainly works on 3 metals:
- Zinc
- Copper
- Iron
The authors noted that the,
"ability of different 8-OHQ's to impinge on diverse proteotoxicities (neurotoxicity caused by overabundant mutant or misfolded proteins) further links metal homeostasis to neurodegenerative diseases including Alzheimer's, Parkinson's and Huntington's diseases."
The potential for this class of drug is huge. Small changes can be made to its chemical backbone, allowing researches to customize it to treat many more brain disorders.
The different varieties of this drug can confer subtle but effective redistribution of metals in the brain. By reorganizing brain metals, researchers could hopefully block poisonous, neurotoxic events. In addition, the right form of this drug should encourage neuro-regeneration, which would help rebuild damaged brain cells.
In real terms, Prana has developed a library of 800 versions of this compound. Three of them are well on their way to becoming real treatments. These are:
- PBT2 as a Phase II candidate for Alzheimer's and Huntington's
- PBT434 for Parkinson's disease
- PBT519 for brain cancer.
Prana's Head of Research, Associate Professor Robert Cherny, commented on the new study,
"This is a landmark paper supporting Prana's therapeutic strategy. The findings by the authors that precise chemical modifications to the 8-OHQ compounds altered metal binding and metal transport properties resulting in various mechanisms of action supports findings by Prana scientists that the therapeutic benefits of selected members of this class of compound arise from a unique combination of metal recovery and redistribution."
Clinical Trials
Prana has already commenced recruitment and screening of patients for a 12 month Phase II Imaging trial testing PBT2, the Company's drug in development for Alzheimer's Disease.
Professor Colin Masters, Director of the Mental Health Research Institute, explained,
"We are selecting patients with established Alzheimer's Disease, as well as targeting those very early in the disease process. We are using the most modern techniques available for measuring PBT2's disease modifying effects to establish cognitive, functional and physical changes in the brain. By disease modifying, I mean modifying the rate of progress of Alzheimer's, slowing it down and delaying onset. We are using PiBPET imaging to measure the drug's effects on the insoluble form of Abeta, and we are using a recently developed blood test to measure levels of the soluble oligomers of Abeta."
"In my opinion PBT2 has the best and highest chance of all drugs currently in development to have a major impact on the disease process, and help avoid the global epidemic of Alzheimer's which, left untreated, is poised to become unmanageable. This trial that is now in progress will establish for the first time not only that PBT2 can improve cognition, as already shown, but that it can actually modify the course of the disease. It will be a major step forward if the drug demonstrates, as I think it will, its ability to affect both soluble and insoluble Abeta levels."
In Huntington's disease, Prana has announced clinical trials opening in Australia and the USA. They will be run by clinical experts at such institutions as Harvard's Massachusetts General Hospital and Johns Hopkins University.
Louise Vetter, CEO of the world's largest Huntington's group, the Huntington's Disease Society of America, enthused,
"We are hopeful and encouraged by Prana's commitment and look forward to the start of recruitment. Patients and families have always been involved in research which fosters a better understanding of this disease and will undoubtedly embrace this new opportunity. We are anxiously awaiting more information on Prana's trial."
Shiralee Judge is the Chairperson of the Australian Huntington's Disease Association. She commented,
"It's very exciting and positive that an Australian company is conducting such extensive research to help us learn more about this disease and to identify a potential treatment to help patients. Huntington's is a very challenging disease, currently without an effective treatment or cure. Patients are very interested in new clinical research and we are looking forward to assisting Prana and their team of researchers with their investigation of PBT2."
The benefits to both Huntington's and Alzheimer's may prove to be powerfully complimentary. In an earlier Alzheimer's clinical trial, PBT2 significantly improved cognitive Executive Function. Huntington's patients also suffer cognitive decline. So there is hope that PBT2 will bring these same cognitive benefits to Huntington's patients.
Prana plans to trial about a hundred people with early stage Huntington's at approximately 15 locations for some six months.
Japanes Patents
In 2011, the Japanese Patent Office granted Prana a composition of matter patent for PBT2 and other selected 8-Hydroxyquinoline compounds in Japan.
Geoffrey Kempler, Prana's Executive Chairman, explained the significance of this particular patent.
"This decision by the Japanese Office to grant a claim to PBT2 completes a suite of core patent rights protecting this asset in key markets including the United States, Europe, Japan and Australia, further bolstering our commercialization plans in both Huntington's and Alzheimer's Disease".
The Japanese patent has a twenty year term expiring on 16 July 2023.
Funding
At the end of the day, the people who arguably understand the real potential of an experimental drug are the people who are paying the bills to develop it. Some impressive backers joined Prana this year, including:
Alzheimer's Drug Discovery Foundation
Private Placement with Rodman & Renshaw, LLC
The backing of the Alzheimer's Drug Discovery Foundation and Quintiles are particularly impressive, as these are two organizations who deeply understand the complexity, history and hurdles of Alzheimer's clinical trials. Their backing sealed PBT2 as the Alzheimer's & Dementia Weekly 2011 Editor's Choice.
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More Information
About Prana Biotechnology Limited
Prana Biotechnology was established to commercialize research into age-related neurodegenerative disorders. The Company was incorporated in 1997 and listed on the Australian Securities Exchange in March 2000 and listed on NASDAQ in September 2002. Researchers at prominent international institutions including The University of Melbourne, The Mental Health Research Institute (Melbourne) and Massachusetts General Hospital, a teaching hospital of Harvard Medical School, contributed to the discovery of Prana's technology.
For further information please visit the Company's web site at www.pranabio.com.
About the Alzheimer's Drug Discovery Foundation
The Alzheimer's Drug Discovery Foundation (ADDF) is the only non-profit organization whose sole mission is to accelerate the discovery and development of drugs to prevent, treat and cure Alzheimer's Disease, related dementias and cognitive aging. Since 1998, the ADDF has granted more than $50 million to fund over 325 Alzheimer's drug discovery programs in academic centers and biotechnology companies in 18 countries. For more information about the Foundation, please visit www.AlzDiscovery.org.
About Quintiles
Quintiles is a leading global clinical research provider.
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