Intravenous AAV dosing improves cardiac and respiratory function in Pompe disease

Lauren Duncanson and Bhuvna Mahajan have been selected for oral presentations to present recent work showing efficacy following systemic AAV-GAA administration

Intramuscular dosing to improve neuromuscular function

Direct administration of AAV9 results in high transduction of myofibers and results in long-term expression of transgene. We are actively pursuing this and alternative routes to maintain and enhance neuromuscular […]

Enhancing NMJ analysis

We are actively working on enhancing the acquisition and analysis of the NMJ. This will allow higher resolution of preparations and determination of pathogenesis or regenerative properties of the NMJ.

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Research projects in our laboratory are united in trying to understand the mechanisms regulating dissociation of the neuromuscular junction in neuromuscular disease. Research in the lab utilizes multiple animal models to understand how pathology stimulates a degenerative response at the neuromuscular junction and whether this is driven independently or in coordination by the peripheral nerve and skeletal muscle. We study these features across multiple levels (i.e. molecular biology - in vivo physiology) while incorporating adeno-associated virus (AAV) vectors to deliver therapy and ultimately restore neuromuscular function.

Neuromuscular Junction

Alterations in the pre- and post-synapse

Alterations in the pre- and post-synapse

Widespread disruption of diaphragmatic neuromuscular junctions in Pompe subjects.
Confocal images of acetylcholine receptor distribution in the diaphragm of representative (A and C) 9-month-old old wild-type 129SVE and (B and D) age-matched Gaa-/- mice. Lower magnification images from the same tissue samples show triple immunolabeling with anti-NFH (magenta), anti-synaptotagmin (green) and alpha-bungarotoxin (red). The white arrow in (C) indicates colocalization of presynaptic synaptotagmin and α-bungarotoxin labeling. (D) Representative area of neuromuscular junctions in Gaa-/- diaphragm show marked reduction in colocalization pre- and post-synaptic labels. White arrows indicate loss of presynaptic staining in motor endplates. Scale bars represent 10 μm.

Lysosomal accumulation in the sciatic nerve

Co-localization of Lamp1 in S100 positive nuclei

Co-localization of Lamp1 in S100 positive nuclei


Localization of lysosomes near Schwann cells in the sciatic nerve of affected animals.

Visualizing the NMJ


Confocal microscopy allows detailed acquisition and quantification of the neuromuscular junction