Use of low doses of hydroxychloroquine for the treatment of lipin-1 deficiency

Abstract

Lipin-1 deficiency is a rare, life-threatening condition that causes severe rhabdomyolysis episodes (RM) triggered by febrile illness and effort. Now, the inventors treated 10 patients with LPIN1 mutations with hydroxychloroquine (HCQ) in an off open-label use phases 1 and 2 study, to assess safety, clinical, and biological effects of the drug. A first inclusion group of patients were treated with oral HCQ at a dose of 6.5 mg/Kg/day in one intake, not exceeding 400 mg/day. Five patients have not presented any new acute RM under treatment, except for 2 patients experimented one and two episodes of RM respectively despite HCQ in a context of gastroenteritis. Plasma levels of HCQ were in the range of 400 ng/ml except in the two patients who experimented RM, in whom the plasma HCQ levels were higher (1000 ng/ml). With a therapeutic adjustment, in order to maintain plasma levels of HCQ under 700 ng/ml, in a new group of patients, two patients did not suffer from new acute RM under treatment. HCQ had not seem to have benefit effect for one patient. Thus, the inventors describe the first human experience with HCQ for Lipin-1 disease. The results allow the inventors to propose low doses of HCQ as a long-term treatment to prevent further relapses in this severe disease.

Dependencies are inferred from the claim text.