• David Merberg, Rodney Moreland, Zhenqiang Su, Bin Li, Bob Crooker, Kathleen Palmieri, Simon W Moore, Andrew Melber, Ruby Boyanapalli, Galen Carey, and Mahindra Makhija.
• Takeda Pharmaceutical Company Limited, Rare Disease Drug Discovery Unit, Cambridge, MA, USA.
• Ann. Med. 2024 Dec 1; 56 (1): 24025032402503.

IntroductionAcid α-glucosidase (GAA) is a lysosomal enzyme that hydrolyzes glycogen to glucose. Deficiency of GAA causes Pompe disease (PD), also known as glycogen storage disease type II. The resulting glycogen accumulation causes a spectrum of disease severity ranging from infantile-onset PD to adult-onset PD. Additional non-invasive biomarkers of disease severity are needed to monitor response to therapeutic interventions.MethodsWe measured protein and miRNA abundance in exosomes from serum and urine from the PD mouse model (B6;129-GaaTm1Rabn/J), wild-type mice, and PD mice treated with a candidate gene therapy.ResultsThere were significant differences in the abundance of 113 miRNA in serum exosomes from Pompe versus healthy mice. Levels of miR-206, miR-133, miR-1a, miR-486, and other important regulators of muscle development and maintenance were altered in the Pompe samples. The serum and urine exosome proteomes of healthy and Pompe mice also differed broadly. Several of the dysregulated proteins are encoded by genes with potential target sites for affected miRNA.ConclusionExosomes derived from urine or serum are a potential source of biomarkers for Pompe Disease. Further study of the differences in the miRNA transcriptome and proteome content of exosomes may yield new insights into disease mechanisms.

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