Efficacy of magnesium chloride in the treatment of Hailey-Hailey disease: from serendipity to evidence of its effect on intracellular Ca(2+) homeostasis.

Abstract

BACKGROUND:

Hailey-Hailey disease (HHD), also known as familial benign chronic pemphigus, is a rare autosomal dominant inherited intraepidermal blistering genodermatosis. Mutations in the ATP2C1 gene encoding for the Golgi secretory pathway Ca(2+) /Mn(2+) -ATPasi protein 1 (SPCA1) affect the processing of desmosomal components and the epidermal suprabasal cell-cell adhesion by deregulating the keratinocyte cytosolic Ca(2+) concentration. We report the unexpected, dramatic, and persistent clinical improvement of the skin lesions of a patient affected with longstanding HHD with daily intake of a solution containing magnesium chloride hexahydrate (MgCl2 ).

MATERIALS AND METHODS:

We investigated the effect of MgCl2 on the intracellular Ca(2+) homeostasis and on the activity of particular Ca(2+) -effectors in HeLa cells transfected with chimeric aequorins (cytAEQ, mtAEQ, erAEQ and GoAEQ) targeted to different subcellular compartments (cytosol, mitochondria, endoplasmic reticulum, and Golgi, respectively).

RESULTS:

Experimental investigations on HeLa cells showed the effect of MgCl2 on the function of Ca(2+) -extrusor systems, resulting in increased cytosolic and mitochondrial Ca(2+) levels, without altering the mechanisms of intraluminal Ca(2+) -filling and Ca(2+) -release of stores.

CONCLUSIONS:

Based on our clinical observation and experimental results, it can be hypothesized that MgCl2 could act as an inhibitor of the Ca(2+) -extruding activity in keratinocytes favoring intracellular Ca(2+) -disponibility and Ca(2+) -dependent mechanisms in desmosome assembly. This may represent the molecular basis of the good response of the HHD clinical features with MgCl2 solution in the patient described.

• Authors: Alessandro Borghi, Alessandro Rimessi, Sara Minghetti, Monica Corazza, Paolo Pinton, Annarosa Virgili
• Journal: International journal of dermatology (Int J Dermatol) Vol. 54 Issue 5 Pg. 543-8 ( 2015) ISSN: 1365-4632 [Electronic] England
• PMID: 25430969 (Publication Type: Case Reports, Journal Article)
• Copyright: © 2014 The International Society of Dermatology.

Chemical References

• Magnesium Chloride
• Calcium

Topics

• Aged
• Calcium (metabolism)
• Cells, Cultured
• Female
• HeLa Cells (drug effects, metabolism)
• Homeostasis
• Humans
• Intracellular Space (metabolism)
• Keratinocytes
• Magnesium Chloride (therapeutic use)
• Pemphigus, Benign Familial (drug therapy, metabolism)
• Treatment Outcome