Daily Supplementation of D-ribose Shows No Therapeutic Benefits in the MHC-I Transgenic Mouse Model of Inflammatory Myositis

Abstract

BackgroundCurrent treatments for idiopathic inflammatory myopathies (collectively called myositis) focus on the suppression of an autoimmune inflammatory response within the skeletal muscle. However, it has been observed that there is a poor correlation between the successful suppression of muscle inflammation and an improvement in muscle function. Some evidence in the literature suggests that metabolic abnormalities in the skeletal muscle underlie the weakness that continues despite successful immunosuppression. We have previously shown that decreased expression of a purine nucleotide cycle enzyme, adenosine monophosphate deaminase (AMPD1), leads to muscle weakness in a mouse model of myositis and may provide a mechanistic basis for muscle weakness. One of the downstream metabolites of this pathway, D-ribose, has been reported to alleviate symptoms of myalgia in patients with a congenital loss of AMPD1. Therefore, we hypothesized that supplementing exogenous D-ribose would improve muscle function in the mouse model of myositis. We treated normal and myositis mice with daily doses of D-ribose (4 mg/kg) over a 6-week time period and assessed its effects using a battery of behavioral, functional, histological and molecular measures.ResultsTreatment with D-ribose was found to have no statistically significant effects on body weight, grip strength, open field behavioral activity, maximal and specific forces of EDL, soleus muscles, or histological features. Histological and gene expression analysis indicated that muscle tissues remained inflamed despite treatment. Gene expression analysis also suggested that low levels of the ribokinase enzyme in the skeletal muscle might prevent skeletal muscle tissue from effectively utilizing D-ribose.ConclusionsTreatment with daily oral doses of D-ribose showed no significant effect on either disease progression or muscle function in the mouse model of myositis.

Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies

“…Blood was collected routinely at 2, 6, and 10 weeks after immunization and at the time of euthanization. Nine weeks after immunization, BW was determined and grip strength for both forelimbs and hind limbs was assessed using a grip strength meter as described elsewhere (65). Sixteen weeks after immunization, mice were euthanized.…”

Role of toll-like receptors in the pathogenesis of dystrophin-deficient skeletal and heart muscle

“…After 5 weeks of treatment (10-week-old mice), blood and tissue samples were harvested from the mice, and in vitro muscle force, serum creatine kinase, and histological data were collected. All the tests were conducted as described previously (18)(19)(20)(21).…”