Metal chaperones: a novel therapeutic strategy for brain injury?

ABSTRACT

Objective: This study sought to assess the potential efficacy of a novel class of metal chaperone on the outcomes in an animal model of a controlled cortical impact. This work was predicated on previous observations that this class of compound has exhibited neuroprotective potential in other models of aging and neurodegeneration.

Research design: The study employed a controlled cortical impact traumatic brain injury in three month old mice with subsequent behavioral and cellular assessments to determine therapeutic efficacy.

Methods: Cognitive (Y-maze) and motor assessments (Rotarod and Open Field) were employed to determine behavioral end points. Histological-based methods were utilized to assess neuronal integrity, astrocytosis, and lesion volume.

Outcomes: We demonstrate here that acute post-injury treatment with PBT2 (Prana Biotechnology) is sufficient to maintain neuronal integrity (evidenced by decreased lesion area and increased numbers of neurons; decreased astrocytosis was also present) and to normalize performance in cognitive testing (Y-maze). These effects occurred within days and were maintained for the entire duration of the study (26 days post-injury). These data support the further interrogation of the utility of metal chaperones for the treatment and/or prevention of the neuroanatomical, biochemical, and behavioral deficits that occur following brain injuries of different etiologies

KEYWORDS:

• Brain injury
• metal chaperone
• cognition
• therapeutic

Acknowledgments

The Florey Institute of Neuroscience and Mental Health acknowledge the strong support from the Victorian Government.

Author disclosure

PAA and DIF are paid consultants and shareholders in Prana Biotechnology. PAA, DIF, PC are variously supported by funds from the National Health and Medical Research Council of Australia, The Australian Research Council and Prana Biotechnology. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Disclosure statement

Paul A. Adlard and David I. Finkelstein are paid consultants and shareholders in Prana Biotechnology. The company played no role in the decision to publish or in the content of the manuscript. In addition, the Florey Institute of Neuroscience and Mental Health acknowledge the strong support from the Victorian Government and in particular the funding from the Operational Infrastructure Support Grant.