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New activity for antitumoral drugs in neurological disorders

Drug reporposingEpilepsyNeurological DisordersNeuronal hyperexcitabilityRiposizionamento farmaciSmall molecule

Introduction

The discovery of a new and unexpected activity in the Central Nervous System of compounds, currently under clinical trials for cancer therapy, opens the possibility of targeting a completely new pathway for the treatment of epilepsy as well as psychiatric disorders caused by neuronal hyper-excitability.

Technical features

Epilepsy is characterized by an aberrant neuronal firing and imbalance in the excitation/inhibition ratio. Current therapeutics are inefficient on 30% of patients, that are left with only palliative cures.We demonstrated that an ATR inhibitor (ATR is a kinase involved in the DNA damage response) can reduce unprovoked neuronal hyperactivity in vitro and seizures severity in vivo preclinical models. The ATR-inhibitor was initially developed as an antiproliferative drug and is currently in clinical trial for cancer treatment. In our invention, the treatment with the ATR-inhibitor induces a shift of the excitation/inhibition ratio toward inhibition and therefore makes ATR an alternative target to interfere with neuronal hyper-excitability. The molecule of the invention can indeed become a candidate drug for drug-resistant epilepsy, anxiety, depression and schizophrenia.

Possible Applications

  • Epilepsy;
  • Anxiety;
  • Depression;
  • Schizophrenia.

Advantages

  • Reduced seizures in preclinical models;
  • Intranasal administration reduces systemic effects;
  • Repurposing of a known molecule reduce time-to-market;
  • Targeting a completely new pathway might overcome resistance to current therapies.