The Effect of Fibrate Therapy in Two Patients With Neutral Lipid Storage Disease With Myopathy (NLSDM)
Status:
Completed
Trial end date:
2012-12-01
Target enrollment:
Participant gender:
Summary
Neutral Lipid Storage Disease With Myopath (NLSDM) is a disease caused by a defect in the
PNPLA2 gene encoding ATGL. Patients with NLSDM accumulate triglycerides and exhibit muscle
weakness, cardiac failure and hepatosteatosis. Most of these patients die at young age due to
cardiac failure. Not much is known about the underlying mechanisms, though recently it was
discovered that PPAR activation in ATGL-/- mice was impaired leading to decreased
mitochondrial function, lipid accumulation and cardiac failure resulting in death at young
age. Activation of PPARs, by treatment with fibrates rescued the phenotype and reduced
mortality rates in these mice. These findings may have a major impact for patients with NLSDM
if these results can be translated to humans. Therefore, the investigators would like to
evaluate the beneficial effects of fibrate treatment on muscle mitochondrial and cardiac
function in patients with NLSDM.
Patients will be treated with fibrates during a period of 28 weeks. Baseline measurements
will be performed prior to the study and after treatment. Cardiac and muscular lipid
accumulation, cardiac function, mitochondrial function and insulin sensitivity will be
assessed during these baseline measurements.