Beta-amyloid and biological metals

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In the recent edition of the journal, Proceedings of the National Academy of Sciences, the multi-institutional team led by Professor David Lynn showed how interactions between beta-amyloid (Abeta) and the biological metals copper and zinc can induce conformational alterations to the Abeta protein causing it to adopt a multitude of toxic forms.

In their article titled "Engineering metal ion coordination to regulate amyloid fibril assembly and toxicity," the authors note that subtle variations in the chemical environment of the brain can radically influence the binding of copper to a specific sequence of Abeta to generate both fibrillar and non-fibrillar (or 'oligomers') forms of the protein. The oligomeric forms of Abeta, in particular, are currently the subject of great interest in the Alzheimer's research community as the best validated therapeutic target in Alzheimer's disease. The authors also emphasize that their findings have relevance to other neurodegenerative conditions including Parkinson's disease, where metal binding is believed to modulate or induce the pathological aggregation of proteins.

Prana scientists, whose work is often cited in this publication, have promoted the concept that changes in brain chemistry associated with the aging process cause subtle fluctuations in the regulation of copper, zinc and iron, permitting toxic interactions with the Abeta protein. Prana's therapeutic approach uses Metal Protein Attenuating Compound (MPAC) technology comprising orally bio-available small molecules which specifically target such pathological interactions. PBT2, the Company's lead compound, was designed to inhibit the formation of toxic oligomers of Abeta resulting from interactions with copper and zinc. PBT2 is currently undergoing an 80 patient, double-blinded Phase IIa Alzheimer's disease clinical trial due to be completed by the end of 2007, and leads from the 400 strong MPAC library are currently being validated for clinical development in other neurodegenerative disorders.

Prana Chairman and Chief Executive Officer, Geoffrey Kempler, remarked, "This report, from an authoritative independent research group, lends further endorsement to the Prana therapeutic approach in neurodegeneration, which is to intercede in the metal dependent process of target protein aggregation." http://www.medicalnewstoday.com

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