There is clear evidence that mitochondrial dysfunction and oxidative stress are precipitating and exacerbating factors in neurodegenerative diseases. The development and commercialization of radio frequency electronics for use in animal models of neurodegeneration to assess oxidative stress is critical to the development of new therapeutics. This technology will be used to identify surrogate markers of disease progression that translate from animals to humans for use in the assessment of therapeutic efficacy in early clinical trials helping to improve time-to-market and save hundreds of millions of dollars in R &D costs. Ekam Imaging Inc. (Ekam) has focused this grant application on developing a 1H/31P radio frequency coil system for use in magnetic resonance spectroscopy to evaluate oxidative stress and mitochondrial dysfunction in animal models of neurodegeneration. In this Phase I application, Ekam will use a rodent model of Parkinson's disease (PD) to test and optimize coil design.
The specific aims are to design and manufacture a prototype rat 1H/31P dual coil system and field test the 1H/31P dual coil system. If successful, a Phase II application will be submitted which will establish this MR spectroscopy technology and its application in a monkey model of PD. Engineers at Ekam will simulate the size, load and electrical properties of a biological object (in this case, an adult rat head) and model the electromagnetic behavior of a coil designed for this specific application. This data will be integrated with RF simulations to predict circuit components for board layouts that will be engineered to fit the product design. Two separate coils, one for 1H and another for 31P will be developed and made interchangeable. Thus, a rat will be imaged first with the 1H coil for high resolution anatomy and 1H spectroscopy (lactate and glutathione specifically) followed by 31P spectroscopy for (phosphate metabolism and pH). Coil simulations will be run with mechanical designs optimized for space filling to accommodate an adult rat head.
The prevalence of neurodegenerative diseases is escalating as the US population ages. With nearly 15% of the US population expected to be 65 or older by 2015, Medicare spending on neurodegenerative diseases (for which there are currently no cures) will reach $190 Billion by that date. Billions of dollars will be spent on the development of new therapeutics for these conditions and critical to this drug discovery process is the use of non-invasive imaging models to study the normal pathophysiology of disease progression.
|Sajo, Mari; Ellis-Davies, Graham; Morishita, Hirofumi (2016) Lynx1 Limits Dendritic Spine Turnover in the Adult Visual Cortex. J Neurosci 36:9472-8|