BCCMA: Recovery of Aged Muscle After Disuse Atrophy (REMEDY): Targeting metabolism to accelerate recovery from disuse atrophy in aged mice

Summary

This project investigates whether AdipoRon treatment can accelerate recovery from disuse muscle atrophy in aged mice, addressing the lack of effective strategies for hospital-acquired muscle weakness in older Veterans.

What they want

The project aims to determine AdipoRon's effectiveness in stimulating skeletal muscle mitochondria to mitigate disuse atrophy and/or accelerate recovery, and to define its life-phase impact on muscle atrophy and recovery, focusing on metabolism and growth processes. Mice of different ages will be treated with AdipoRon during hind limb suspension and recovery phases. Recovery will be assessed at tissue and functional levels, quantifying skeletal muscle contractile function, composition, mitochondrial and lipid metabolism, intramuscular adiposity, fiber shrinkage, and fibrosis. Systemic indices like glucoregulatory function, adiposity, and adipokine/inflammatory signaling will also be measured. The study will employ targeted histological approaches and unbiased molecular approaches including transcriptomics, metabolomics, lipidomics, and kinetic proteomics to define the disuse atrophy and recovery trajectory. Clinical insights will be reverse translated and analyzed against the pathology of disuse atrophy and recovery trajectories with or without AdipoRon treatment.

Deliverables

Determination of AdipoRon's effectiveness in mitigating disuse atrophy and/or accelerating recovery
Definition of AdipoRon's life-phase impact on muscle atrophy and recovery
Quantification of skeletal muscle contractile function, composition, mitochondrial and lipid metabolism, intramuscular adiposity, fiber shrinkage, and fibrosis
Quantification of systemic indices including glucoregulatory function, adiposity, and adipokine and inflammatory signaling
Definition of disuse atrophy and recovery trajectory using molecular approaches
Clinical insights reverse translated and analyzed against pathology of disuse atrophy and recovery trajectory

Technical requirements

AdipoRon treatment
Hind limb suspension model (in mice)
In vivo and ex vivo measurements
Quantification of skeletal muscle contractile function
Quantification of muscle composition
Quantification of mitochondrial and lipid metabolism
Quantification of intramuscular adiposity
Quantification of fiber shrinkage and fibrosis
Quantification of glucoregulatory function
Quantification of adiposity

Market context

inferred from NAICS

Professional, Scientific & Technical Services

NAICS 541714

US market size: $2.0T
Typical award: $25K – $50M

Typical buyers

All federal civilianDoDStates

Commonly required

8(a)WOSBSDVOSBPE/PMP

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