The first MAPTA (Modeling Alliance of Systems Pharmacology in TAuopathies) Workshop held on May 26, 2017 in Washington, D.C. brought together key thought leaders and computational modeling experts from academia and industry to advance tauopathy research for TBI and other neurodegenerative disorders.
The microtubule associated-protein tau is a key driver of neurodegeneration in Alzheimer’s disease and other neuropathologies, such as Traumatic Brain Injury (TBI), which have few or no treatment options. Despite thousands of preclinical studies published on tau, few therapeutic trials have been conducted due to the complexity of the target.
To better understand the role of tau in brain disease, Cohen Veterans Bioscience in partnership with In Silico Biosciences formed the MAPTA Alliance to drive efforts in developing predictive models of brain disease. This will be achieved by building mechanistic models based on Quantitative Systems Pharmacology (QSP) approaches and by integrating Causal Knowledge Base models such as the TBI Knowledge MapTM. Immediate goals of the one-day workshop included:
Dr. Magali Haas of Cohen Veterans Bioscience highlighted the proposed 3-year scientific roadmap for MAPTA, which includes exploring the intracellular function of tau (Year 1), understanding the trans-synaptic spreading of tau pathology through the brain (Year 2), and using tau’s known synaptic function to study neuronal network models relevant to TBI (Year 3).
During this process, MAPTA aims to recruit additional Alliance partners and align modeling efforts with areas of interest to industry. As described by Dr. Hugo Geerts of In Silico Biosciences, MAPTA is spearheading actionable deliverables, including a temporal model of intra-neuronal tau pathology in combination with a spatial-temporal model of human tauopathy progression with the end goal of bridging the gap between fundamental science and clinically relevant research.
As evidenced by discussion at the MAPTA Workshop, we are currently seeing only the tip of the iceberg with respect to tau pathology. In opening his talk on tau neurobiology, Dr. Kenneth Kosik, a professor in neuroscience at the University of California at Santa Barbara, expressed hope about tau as a possible druggable target: We’ve been in Death Valley for some time in this field, but I feel optimistic as we start thinking about tau in novel ways.” However, the difficulty resides in developing an in-depth understanding of the pathophysiological mechanisms of
key tauopathies prior to modeling attempts. Indeed, the development of effective computational tools with the goal to optimize the selection of putative targets require the gathering and evaluation of the existing knowledge space and the identification of key knowledge gaps. The alliance will work together to pursue this goal.
Members of MAPTA’s Scientific Advisory Board discussed areas of opportunities for modeling neuropathology. Some highlights include:
To build on momentum from this workshop, working group meetings are planned for the second half of 2017. Through these on-going discussions, the MAPTA Alliance will start integrating preclinical and clinical data on tau biology into computational modeling efforts, prioritizing model development based on (1) the strength of the scientific literature, (2) appropriateness for modelling, and (3) relevancy from a drug discovery and development perspective. The objective is to develop a comprehensive and actionable modeling platform for identifying and validating druggable targets for tauopathies.
If you are interested in more details or would like to join the MAPTA Alliance, please contact [email protected].
Cohen Veterans Bioscience is a non-profit 501(c)(3) biomedical research and technology organization dedicated to advancing brain health by fast-tracking precision diagnostics and tailored therapeutics.