Mevalonate kinase deficiency: therapeutic targets, treatments, and outcomes

Annalisa Marcuzzi, Elisa Piscianz, Liza Vecchi Brumatti, Alberto Tommasini

Research output: Contribution to journalReview articlepeer-review


Introduction: Mevalonate Kinase Deficiency (MKD) is a rare inborn disease caused by the mutation of mevalonate kinase gene. The clinical phenotype encompasses recurrent fever episodes in combination with gastrointestinal, immunological, rheumatological and neurological complaints. No specific treatment is available, apart from the newly approved biologics (canakinumab), but MKD can be still considered an orphan-drug disease, since the identification of a reliable therapeutic target needs an improved knowledge on the pathogenesis of the disease, which is so far controversial. Areas covered: On one hand, shortage of isoprenoid compounds downstream of mevalonate led to a defective geranylgeranylation of RhoA/Rac proteins and increased caspase-1-dependent inflammation. On the other hand, recent studies pointed the attention to the pathogenic role of the mitochondrial dysfunction and to defective production of 25-hydroxycholesterol. These mechanisms are not exclusive of each other, as they can contribute to different pathogenic features of MKD. Expert opinion: Innovative therapeutic approaches to MKD may count upon various medicaments, such as isoprenoid compounds that can enter the metabolic pathway, specific enzyme inhibitors and mitochondria-targeted drugs. Some of these compounds have already passed the clinical phase for other uses and may be repositioned to the treatment of MKD, fostering the development of clinical trials.

Original languageEnglish
Pages (from-to)515-524
Number of pages10
JournalExpert Opinion on Orphan Drugs
Issue number6
Publication statusPublished - Jun 3 2017


  • cholesterol
  • immunology
  • inflammation
  • Rare disease

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
  • Health Policy
  • Pharmacology (medical)


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