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Mimetic peptides for restoring L-type Calcium channels

Cardiac failure and arrhythmiaContractilityIntracellular CalciumL-type calcium channelNeurotransmitter

Introduction

The present invention concerns peptides which are suitable for use in the treatment of conditions where the L-type calcium channel (LTCC) density and function is altered. The mimetic peptides (MPs) identify, based on a novel and physiologic molecular mechanism, a therapeutic tool for the treatment of human diseases associated with altered LTCC-dependent cellular Ca2+ homeostasis such as cardiovascular, neurological and urological diseases.

Technical features

Researchers at the CNR IRGB Institute have identified within the intracellular protein subunit (Cavβ2) of the L-Type Calcium Channels (LTCCs), a regulatory domain and corresponding selective binding peptides. Specific binding of the peptide to the domain activates a physiological mechanism of action that restores the LTTC density and function at the cellular plasma membrane. Without altering  the LTCC electrophysiological properties, the peptide eventually restore the intracellular calcium levels, and thus cell functions, otherwise compromised by the unfunctional LTCCs. The invention claims a specific peptide which, by binding to the above-mentioned domain, modulates those calcium-dependent cellular processes. Field of application are all those acquired or genetic-based pathologies in which the levels of intracellular calcium and LTCC density are altered.

Possible Applications

  • Cardiology (diabetic cardiomyopathy, fibrillation, Brugada syndrome, cardiomyopathy associated with hyper / hypothyroidism, cardiac hypertrophy, hyper / vascular hypotension, myocardial ischemia, angina pectoris);
  • Neurology (Alzheimer’s, Parkinson’s);
  • Ophthalmology (glaucoma);
  • Urology (bladder dysfunction, incontinence).

Advantages

  • Specificity of action for the L-type Calcium Channel (LTCC);
  • Physiological mechanism of action;
  • Dynamic (and reversible) restoring modulation of the dysregulated LTCC;
  • No supraphysiologic effect;
  • No alteration of LTCC electrophysiological properties;
  • Multiple via of administrations;
  • Many different applications in medicine.