Bethlem Myopathy Clinical Trial
Official title:
Low Protein Diet to Correct Defective Autophagy in Patients With Collagen VI Related Myopathies
- This is a 2 stage exploratory study with a 3-month observational phase on the natural
course, followed by a 12-month, open-label, non-comparative, single-arm, phase II pilot
study on the efficacy, safety and tolerability of a low-protein diet (LPD) in 8 adult
patients with Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD).
- Objective of this trial is to test the effect of a normocaloric LPD to reactivate
autophagy in BM/UCMD patients. The primary end point of the study will be the change in
muscle biopsy of Beclin 1, a marker of autophagy, at 1 year of LPD treatment when
compared to baseline.
- The rationale rests on our discoveries that (i) mitochondrial dysfunction mediated by
inappropriate opening of the PTP plays a key role in collagen VI myopathies; (ii)
defective autophagy with impaired removal of defective mitochondria amplifies the
defect; and (iii) reactivation of autophagy with a low-protein diet or treatment with
cyclosporine A, the mitochondrial PTP inhibitor, cured Co6a1-/- mice, hinting at a
common target among all beneficial treatments - namely autophagy.
- Specific aims of this project are to (i) study the modifications of clinical,
nutritional and laboratory parameters in a cohort of patients with BM/UCMD during a
3-month observational period before starting the LPD treatment; (ii) assess the effect
of a normocaloric LPD in correcting defective autophagy in muscle of patients; (iii)
test if new non-invasive biomarkers of activation of autophagy examined in the blood
are mirroring the effect of LPD in the muscle biopsy; (iv) assess the clinical efficacy
and safety of the LPD with an innovative combination of complementary measures of the
nutritional status in patients.
- The anticipated output is defining and validating a therapeutic nutritional approach in
autophagy upregulation for BM/UCMD.
n/a
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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