Neutral Lipid Storage Disease
Conditions
Keywords
NLSDM, Lipid accumulation
Brief 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.
Interventions
DRUGFibrate treatment
Patients will receive a dosage of 400mg Bezafibrate every day during 28 weeks
Sponsors
Maastricht University Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* suffering from NLSDM
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| mitochondrial function | 28 weeks | mitochondrial function will be measured in vivo with 1H-MRS by pCr-recovery and ex vivo by high resolution respirometry. |
| lipid accumulation | 28 weeks | Lipid accumulation will be measured both by 1H-MRS as CH/H2O ratio's in the Tibialis anterior muscle, as well as quantified from skeletal muscle biopsy with ORO from the vastus lateralis muscle. |
| Cardiac function | 28 weeks | Cardiac function will be measured with ultrasound and be assessed by 2 blinded cardiologists. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insulin sensitivity | 28 weeks | This will be assessed by an euglycemic hyperinsulenemic clamp and whole body isulin sensitivity will be expressed with the M-value. |
Countries
Netherlands
Outcome results
None listed