Programmable molecular nanorobots for treatment of chronic pain and epilepsy

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Proper detection and processing of information in the nervous system is highly dependent on the ability of neuronal network to control and regulate the excitability levels of individual neurons (intrinsic excitability) and the synapses that connect them into a functional network (network excitability). Regulation of the excitability is crucial for the ability of the circuits to adapt to changes in the environment, whereas uncontrolled alteration of intrinsic and network excitability leads to severe interruption of normal neuronal function. The archetypical manifestations of such uncontrolled changes are expressed as chronic pain and epilepsy. These devastating medical conditions reaching pandemic scale, lead to extreme suffering, as well as to exorbitant medical expenses. Despite extensive efforts, effective treatment for chronic pain and epilepsy remains elusive. It is absolutely necessary to design treatment strategies which selectively targets aberrant processes causing chronic pain or epileptic seizures. Here, we propose to use novel, ground-breaking technologies to detect and control these types of abnormal neuronal activity. To that end, we will design programmable DNA nanorobots that can sense specific modes of neuronal activity and respond by releasing selected modulators, thus affecting only pathological events, while sparing normal functions. Using DNA nanorobots, we will attempt to interfere with pain and seizure generation at multiple levels. This multi-disciplinary project will incorporate cutting edge nano-technologies together with electrophysiological, multiphoton imaging and behavioural methodologies, which have been fine-tuned to study and control pain- and epilepsy-reIated mechanisms. The results of this proposal are expected to provide a basis for novel platforms for treating chronic pain and epilepsy, as well as to yield fundamental insights into themechanisms of hyperexcitable states.