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Huntington's Disease

Prana Comments on Archives of Neurology Publication Which Highlights Critical Role of Brain Metals in Huntington Disease Progression: MGH team publishes data that supports the use of PBT2 in Huntington disease

Melbourne – 1 May 2012: Prana Biotechnology (NASDAQ:PRAN; ASX:PBT) today commented on the publication of new data of relevance to the current clinical trial, testing Prana’s PBT2 as a treatment for Huntington disease.

The authors of the publication are led by Professor Diana Rosas of the Center for Neuroimaging of Aging and Neurodegenerative disease at Massachusetts General Hospital (MGH) in Boston. The paper, entitled “Alterations in Brain Transition Metals in HD”, published in the Archives of Neurology* describes how the rise in levels of Iron in the brains of people carrying the mutant gene which causes Huntington disease, correlates with the severity of symptoms and also predicts the time of disease onset. The article concluded that “an important and early role of altered metal homeostasis is suggested in the pathogenesis of Huntington disease” and this points to “metals as potential therapeutic targets”. Selected patients in the current Reach2HD trial, testing PBT2, will be monitored using the imaging technology described in the publication.

According to Professor Rudy Tanzi, Prana’s Chief Scientific Advisor and the Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard University, "The new findings serve to further support the role of brain metal imbalances in the pathology of neurodegenerative diseases such as Alzheimer's disease and Huntington disease. It is becoming increasingly clear that PBT2 and Prana's other metal chaperone drugs could have broad utility as powerful modifiers of disease progress in a growing number of neurodegenerative diseases caused by misfolded proteins."

Ira Shoulson MD, Professor of Neurology, Pharmacology and Human Science at Georgetown University (Washington DC) and the Chair of the Executive Committee of the Huntington Study Group said “The data from the Harvard group are very encouraging and timely. The Reach2HD trial is underway and intended to characterize the safety and dosing parameters of PBT2, an experimental drug aimed at restoring function to neurons damaged by the pathological interaction between the mutant Huntingtin protein and transition metals. PBT2 has signaled some cognitive benefit in patients with Alzheimer disease that may also involve a pathological interaction between a protein and transition metals.”

Huntington disease is a complex and severely debilitating genetic, neurodegenerative disease, for which there is no cure. It is caused by an abnormally high number of repeats of a DNA sequence (CAG) which encodes for the amino acid glutamine. The disease often affects young adults and, whilst associated with severe physical movement symptoms, progressively impacts the mind and emotions as well. The disease causes incapacitation and death about 15-25 years after onset. The disease affects 30,000 people in the US and about 70,000 worldwide.

There are no drugs either available or in development that have established clinical evidence for treating the cognitive decline associated with Huntington disease. In this study, Prana aims to demonstrate cognitive improvements as already demonstrated in a Phase IIa study in mild Alzheimer’s patients treated with PBT2. The study will also investigate safety, functional, behavioural and motor benefits in this Huntington patient population.

PBT2 is concurrently being tested in a Phase II trial in Alzheimer’s disease.

Key points from the publication

Using an advanced non-invasive MRI Imaging technique with pre-symptomatic and symptomatic patients, the authors show that:

  • Iron levels in specific brain areas rise before symptoms appear and correlate with disease severity
  • Iron levels increase with increased CAG repeat length
  • Presymptomatic iron levels predict age of onset of symptoms

The authors found that the MRI data correlated well with the levels and anatomical distribution of iron in postmortem brain tissue.

** Rosas HD, Chen YI, Doros G, Salat DH, Chen N-k, Kwong KK, Bush A, Fox J, Hersch SM (2012) Alterations in Brain Transition Metals in Huntington disease: An Evolving and Intricate Story. Arch Neurol archneurol.2011.2945.