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Disruption of Adenosine Homeostasis in Epilepsy and Therapeutic Adenosine Augmentation

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Adenosine

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Abstract

Despite the development of new classes of antiepileptic drugs during the past 40 years, about a third of all patients with epilepsy continue to be refractory to conventional treatment. It becomes evident that a disorder of complex network dysfunction, such as epilepsy, cannot be treated in a comprehensive manner with traditional treatment approaches. In contrast, the homeostatic bioenergetic network regulator adenosine is uniquely suited to affect several different pathways and mechanisms synergistically on multiple different levels. Adenosine is a known endogenous anticonvulsant of the brain. Its levels rise during seizures, and this increase in adenosine is part of an endogenous control mechanism to terminate seizures. However, disrupted adenosine homeostasis and resulting adenosine deficiency is a pathological hallmark of the epileptic brain. Adenosine deficiency as such was recently shown to be sufficient to trigger seizures. Thus, adenosine augmentation therapy (AAT) is a rational intervention to treat epilepsy. Unfortunately, systemic AAT is not a therapeutic option due to unacceptable side effects. To circumvent this problem, focal AATs have been developed based on the rationale to reconstruct normal adenosine homeostasis within an epileptogenic brain.

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Acknowledgement

The work of the author is supported by grants R01NS058780, R01NS061844, and R01MH083973 from the National Institutes of Health (NIH).

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  1. RS Dow Neurobiology Labs, Legacy Research Institute, 1225 NE 2nd Ave, Portland, OR, 97232, USA

    Detlev Boison Ph.D.

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  1. Trinity College, 300 Summit Street, LSC 208, Hartford, 06106, USA

    Susan Masino

  2. Legacy Research Institute, Portland, OR,, 1225 NE 2nd Avenue, Portland, 97232, USA

    Detlev Boison

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Boison, D. (2013). Disruption of Adenosine Homeostasis in Epilepsy and Therapeutic Adenosine Augmentation. In: Masino, S., Boison, D. (eds) Adenosine. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3903-5_26

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