公开(公告)号：US20230066065A1

公开(公告)日：2023-03-02

申请号：US17797265

申请日：2021-02-04

申请人： Institut National de la Santé et de la Recherche Médicale (INSERM) ,  Assistance Publique-Hôpitaux de Paris (APHP) ,  Centre National de la Recherche Scientifque (CNRS) ,  Fondation Imagine ,  Université Paris Cité

发明人： Pascale DE LONLAY-DEBENEY ,  Peter VAN ENDERT ,  Sebastian MONTEALEGRE ,  Caroline TUCHMANN-DURAND ,  Laure CACCAVELLI ,  Marine MADRANGE ,  Perrine RENARD

IPC分类号： A61K31/4706 ,  A61P3/00

摘要： 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.