Translational Science

Projects

A Phase 2 Study to Evaluate the Impact of MTP-131 (elamipretide) on Skeletal Muscle Function in Elderly (MOTION) (NCT02245620)

Loss of mitochondria function results in exercise intolerance and is a key factor in the disability that develops in aging and chronic disorders. In mice, single dose of SS-31 (same active compound as ELAM) improves in vivo mitochondrial energetics and muscle function in aged mice after only one hour and 8 weeks of treatment (Siegel et al. 2013; Campbell et al. 2019). In human, we found a single dose of ELAM elevated mitochondrial capacity immediately after 2 hr infusion. This result demonstrated ELAM improves mitochondrial dysfunction immediately after treatment in aging human muscle (Roshanravan et al. Preprint).

The impact of daily dose of an Astaxanthin formulation alone with exercise training on skeletal muscle function in the elderly (complete)

Building strength and endurance has been a challenge in exercise training in the elderly. A daily oral dose of Astaxanthin (AX) with interval training improved muscle strength and size (figure) in addition to the elevation in endurance found with training alone in healthy elderly (Liu et al. 2018).

Changes in muscle properties after 3 month of training in AX and placebo. MVC (maximum voluntary contraction, muscle strength) CSA (cross sectional area, muscle size) specific force ( MVC/CSA).

Evaluate skeletal muscle mitochondrial bioenergetics and physical performance in chronic kidney disease

Defects in mitochondrial energetics may impair skeletal muscle function and compromise physical performance and contribute to poor quality of life in CKD patients. In collaboration with the UW Kidney Research Center we compared in vivo mitochondrial function between CKD and healthy age-matched control subjects. We found that in vivo mitochondrial energetics were disrupted in the skeletal muscle of the CKD patients relative to controls. This suggests that one of the consequences of declining kidney function is skeletal muscle mitochondrial dysfunction that then can contribute to further physiological decline and loss of mobility leading to a downward spiral of function. (article in review)

Bioenergetics and Muscle Function Improvement With AMAZ-02 in Elderly Skeletal Muscle (ENERGIZE Trial) (NCT03283462)

Functional food and food supplements are increasingly being developed to deliver bioactive natural ingredients to mitigate pathophysiology of disease and improve health. Work from collaborators indicates that treatment with urolithin A, a natural compound that stimulates mitophagy, extended lifespan in worms and improved muscle function in adult mice and improved endurance and muscle strength in old animals (Ryu et al. 2016). We are conducting a clinical trial to test whether supplementing with urolithin A (AMAZ-02) for 4 months improves muscle performance, in vivo muscle energetics, and exercise tolerance in the elderly. (ongoing)

Functional and metabolomic biomarkers of mitochondrial dysfunction in Parkinson’s Disease (ongoing)

The goal of this study, sponsored by the Michael J. Fox Foundation for Parkinson’s Research, is to use unique in vivo assessment of metabolic fluxes and metabolite biomarkers assessed with 31P MRS to identify the unique signature of bioenergetics markers and mitochondria dysfunction in muscle of individuals with Parkinson’s Disease (PD) compared with healthy aging population. (ongoing)

Study of Muscle, Mobility and Aging (SOMMA) (ongoing)

SOMMA logoThis is a multisite study: Evaluate the role of age related biological changes in skeletal muscle on the decline in mobility.  Our center is to provide a standardized approach for characterizing mitochondrial and cell energetic properties in vivo across multisites. To train personnel in MR spectorosocy and imaging across multiple data collecting sites , implement a standard exercise protocol , measure phosphorus metabolite dynamics and muscle size/mass; provide quality control for acquired spectra and images and auantify phosphorus metabolites, PH, ATPflux and muscle mass.