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A therapeutic use of NAADP and/or TPC2 antagonists

Calcium ionscovid-19Growth factorsIntracellular trafficLysosomal ion channelsPathological neoangiognesis

Introduction

Using different experimental models, it has been shown that the signaling mechanism of the TPC2 ion channel controls a specific intracellular pathway of the angiogenic response of endothelial cells to the VEGF receptor (VEGFR2). These data present a new, highly selective molecular target for the development of innovative therapies in diseases characterized by excessive and unwanted neovascularization, i.e., tumors and inflammation.

Technical features

The invention covers the identification of a crucial molecular target in important pathologies and proposal for therapeutic uses for its inhibition. The experimental results indicate that the intracellular signalling pathway that converges on the lysosomal ion channel TPC2 is crucial in the control of tumor growth, neoangiogenesis and coronavirus viral infection. Considering these data, TPC2 represents an important new drug target that could be exploited for cancer and infectious therapy. To date, the antiangiogenic therapies used inhibit the entire receptor machinery of VEGF (angiogenic but also antiangiogenic), offering short-term benefits. The inhibition of the VEGF angiogenic response alone through the TPC2 pathway offers a therapeutic specificity that is not achievable with current therapies. It is emphasised that the biological effects mediated by the activation of this ion channel were countered.

Possible Applications

  • Oncological and infectious therapy;
  • Development of innovative antiangiogenic therapies;
  • Anti-SARS-CoV-2 prophylaxis / therapy;
  • Formulation as a nasal spray containing a TPC2 inhibitor (e.g. naringenin).

Advantages

  • Therapeutic specificity;
  • Identification of a natural substance, Naringenin, capable of inhibiting TPC2;
  • Naringenin inhibitor of both VEGF-mediated angiogenesis and coronavirus infection.