Temperature and drug treatments in mevalonate kinase deficiency: An Ex vivo study

Paola Maura Tricarico, Giulio Kleiner, Elisa Piscianz, Valentina Zanin, Lorenzo Monasta, Sergio Crovella, Annalisa Marcuzzi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Mevalonate Kinase Deficiency (MKD) is a rare autosomal recessive inborn disorder of cholesterol biosynthesis caused by mutations in the mevalonate kinase (MK) gene, leading to MK enzyme decreased activity. The consequent shortage of mevalonate-derived isoprenoid compounds results in an inflammatory phenotype, caused by the activation of the NALP3 inflammasome that determines an increased caspase-1 activation and IL-1β release. In MKD, febrile temperature can further decrease the residual MK activity, leading to mevalonate pathway modulation and to possible disease worsening. We previously demonstrated that the administration of exogenous isoprenoids such as geraniol or the modulation of the enzymatic pathway with drugs, such as Tipifarnib, partially rescues the inflammatory phenotype associated with the defective mevalonic pathway. However, it has not been investigated yet how temperature can affect the success of these treatments. Thus, we investigated the effect of temperature on primary human monocytes from MKD patients. Furthermore the ability of geraniol and Tipifarnib to reduce the abnormal inflammatory response, already described at physiological temperature in MKD, was studied in a febrile condition. We evidenced the role of temperature in the modulation of the inflammatory events and suggested strongly considering this variable in future researches aimed at finding a treatment for MKD.

Original languageEnglish
Article number715465
JournalBioMed Research International
Volume2013
DOIs
Publication statusPublished - 2013

Fingerprint

mevalonate kinase
Mevalonate Kinase Deficiency
Drug therapy
tipifarnib
Temperature
Mevalonic Acid
Pharmaceutical Preparations
Terpenes
Fever
Inflammasomes
Modulation
Phenotype
Therapeutics
Caspase 1
Interleukin-1
Chemical activation
Monocytes
Cholesterol
Biosynthesis
Enzyme activity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)

Cite this

Temperature and drug treatments in mevalonate kinase deficiency : An Ex vivo study. / Tricarico, Paola Maura; Kleiner, Giulio; Piscianz, Elisa; Zanin, Valentina; Monasta, Lorenzo; Crovella, Sergio; Marcuzzi, Annalisa.

In: BioMed Research International, Vol. 2013, 715465, 2013.

Research output: Contribution to journalArticle

Tricarico, Paola Maura ; Kleiner, Giulio ; Piscianz, Elisa ; Zanin, Valentina ; Monasta, Lorenzo ; Crovella, Sergio ; Marcuzzi, Annalisa. / Temperature and drug treatments in mevalonate kinase deficiency : An Ex vivo study. In: BioMed Research International. 2013 ; Vol. 2013.
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