Further Information - Prana’s PBT2 Clinical Trials Cited as Most Advanced in Addressing Neurodegeneration from the Metal Equilibrium Perspective
Melbourne – September 20, 2012; Prana Biotechnology (NASDAQ:PRAN; ASX:PBT) today reported that it had been cited in an interview in The Life Sciences Report with George Zavoico, Ph.D., senior equity analyst and managing director with MLV & Co., as the only drug company to address in clinical trials the control of transition metal levels in neuronal synapses, a key event in age-related dysfunction of the brain. The Report citing Prana is titled, “Seven Innovative Biotechs That Could Soar By Year- End”.*
Further information regarding MLV & Co & Prana is provided below.**
In the published interview, Dr. Zavoico spoke about an emerging hypothesis addressing the formation of beta amyloid plaques, and how another neuronal protein, tau, is hyperphosphorylated, enabling it to form neurofibrillary tangles. These are recognized by experts in the field as key events in age-related brain dysfunction and cognitive loss. The basis for what has been called the “Metals Dyshomeostasis Hypothesis” is the abnormal distribution and loss in the control of transition metal levels in neuronal synapses. Dr. Zavoico said, “Metals like zinc, copper and iron have a number of important biologic functions, most notably in the function of numerous enzymes and receptors. Zinc, in particular, binds to beta amyloid, leading to its aggregation and, ultimately, plaque formation”.
Moreover, studies have shown that abnormal distribution of transition metals driven partly by beta amyloid plaque formation affects the function of tau, an intracellular protein essential for normal neuronal function. Tau becomes hyperphosphorylated and forms neurofibrillary tangles, which is thought to cause neuronal cell death.
Prana is evaluating the potential clinical benefit of PBT2 in two Phase II trials in two different neurodegenerative diseases. In Alzheimer’s disease, the IMAGINE trial, a double-blind placebo controlled trial enrolling 40 patients with prodromal or mild Alzheimer’s disease, being treated for 12 months will test cognition and use brain imaging to measure the effects of PBT2 on beta-amyloid deposits in the brain and effects on increasing brain activity.
In the interview, Dr. Zavoico added: “In preclinical studies, Prana's lead drug candidate, PBT2, has been shown to redistribute zinc and other transition metals, preventing beta amyloid aggregation and even inducing its disaggregation. Sequestration of zinc in beta amyloid plaques reduces zinc levels inside the neuron, which can lead to its [tau protein’s] hyperphosphorylation. The metals hypothesis appears to unify the pathology underlying both amyloid plaque and neurofibrillary tangle formation, which makes this approach so compelling, in my mind”.
Notably, Huntington’s disease is also characterized by misfolding and aggregation of proteins, but of Huntingtin protein, not beta amyloid. Like Alzheimer’s, studies indicate that the pathology underlying Huntington’s disease is also due to abnormal distribution of certain transition metals. The Reach2HD trial, enrolling 100 patients with early to mid- stage Huntington’s disease, being treated for 6 months, aims to demonstrate safety, motor and behavioural benefits and the same cognitive benefits for Huntington’s patients that it has already demonstrated in Alzheimer’s patients treated with PBT2. Results of Prana’s clinical trials are expected in the second half of next year.
Prana’s CEO, Geoffrey Kempler, commented that “it is very encouraging that the strength of our science and the clinical potential of PBT2 is being recognized by industry experts and analysts, particularly at a time when so many competing drug candidates to treat Alzheimer’s have failed to meet their clinical endpoints. As some researchers are losing hope that Alzheimer’s can even be treated, we remain very confident in the potential of PBT2 to help patients”.
*The Life Sciences Report, A Streetwise Report, September 13, 2012.
**The Life Sciences Report, A Streetwise Report interview with Dr Zavoico follows an Equity Research Life Sciences Biotechnology Company Update of MLV & Co LLC dated August 10, 2012. A copy of the initial report is available on the Company’s website at www.pranabio.com. MLV & Co LLC is a New York based full service investment bank which, as previously announced, has acted and continues to act and receive fees as a broker to the Company.