In May 2024, Xuhui Liu (co-director of the Feeley-Liu Lab) was awarded the UCSF Resource Allocation Program grant for research of FAP (Fibro Adipogenic Progenitor) in neuromuscular junction health (NMJ) with Amyotrophic lateral sclerosis (ALS). The grant will be used to investigate FAP mitochondria biosynthesis and transfer during muscle denervation and NMJ degeneration in ALS, and to determine the role of FAP mitochondria transfer in muscle and NMJ health in ALS muscle.

ALS is a severe neurodegenerative disease marked by progressive muscle weakness and dysfunction, affecting movement, swallowing, speaking, and breathing. Research suggests that ALS pathology may start at the neuromuscular junction (NMJ) in muscles rather than motor neurons, with muscle denervation preceding motor neuron abnormalities. 

FAP cells play a key role in muscle health, aiding in muscle regeneration and homeostasis. FAPs, which expand in response to injury, can both support muscle repair and contribute to fibrosis and fat deposition in chronic damage conditions. They also help stabilize the NMJ, with their depletion leading to muscle weakness and NMJ deterioration.

Mitochondrial dysfunction is linked to ALS. Research shows mitochondria can be transferred between cells, helping restore function in damaged tissues. FAPs can transfer mitochondria to muscle cells post-injury, promoting regeneration. This study aims to explore mitochondrial transfer as a mechanism for FAPs to support muscle and NMJ health in ALS.

In this study, Dr. Liu will revise previous studies on mitochondrial transfer and will use a new mouse model to track FAP mitochondria in ALS. Dr. Liu believes FAPs transfer mitochondria to muscle cells, satellite cells, and neuromuscular junctions to combat muscle and nerve degeneration in ALS. He also seeks to understand the exact role of FAP mitochondrial transfer in muscle and nerve health. To study this, he'll give these drugs to ALS mice and observe how they impact mitochondria transfer, muscle and nerve degeneration, limb function, and disease progression. This will help Dr. Liu determine the functional role of FAP mitochondria transfer in ALS.

This experiment holds the promise of providing compelling evidence for in vivo FAP mitochondria transfer in ALS, representing a significant advancement in our understanding of this phenomenon.