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The role of Adamts in Cerebral Cavernous Malformation (CCM) disease

posted on April 15, 2019
Research Breakthroughs
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In the project above, I planned to test whether genetically and pharmacologically inhibiting Adamts in CCM disease can be utilised as a therapeutic target for Cerebral Cavernous Malformations (CCMs).

Since I received the grant, I have identified an FDA approved drug, Ponatinib, which can effectively target MEKK3-KLF-ADAMTS pathway to prevent CCM formation and growth in experimental mouse models. This work has been published in a highly regarded journal Science Advances (http://advances.sciencemag.org/content/4/11/eaau0731) in November 2018.

Meanwhile, I have continued the work to directly intervene ADAMTS activity. I concluded that genetic deletion of ADAMTS5 gene inhibited CCM lesion formation in mice with CCM2 mutations but not in CCM1 mutations. Suggesting, mutation specific role of ADAMTS5 CCM disease. Hence, I aim to investigate other family of ADAMTS proteins which maybe universally involved in CCM pathogenesis.

Part of the data generated from this project is used my grant applications in National Health and Medical Research Council of Australia (NHMRC) which is NIH equivalent in Australia. I expected to find the outcomes of these grants by end of 2019.

– Dr Jaesung P. Choi,

Locked Bag 6, Newtown NSW 2042 Australia | p 1800 677 977 | w centenary.org.au Affiliated with the University of Sydney and Royal Prince Alfred Hospital Centenary Institute Medical Research Foundation ABN 85 778 244 012 (DGR 2) • Centenary Institute ABN 22 654 201 090 (DGR 1)

Laura Callen

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