An adeno-associated virus serotype 9 (AAV9) vector encoding a DREADD delivered on the tongue leads to the expression of the DREADD in motor neurons, a new study conducted in a mouse model of Pompe disease showed.

DREADD stands for “designer receptors exclusively activated by designer drugs” and in this case consisted of a designer receptor specific to astrocytes under a human synapsin promoter. 

Twelve weeks after the researchers injected the DREADD ligand intralingually in the mice, they found there was a statistically significant increase in inspiratory electromyogram activity recorded from the back of the tongue. There was no such increase in control animals injected with a control saline solution. 


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The analysis of the animals’ brainstems showed that the construct was present in the hypoglossal (XII) motor neurons in all the animals, “thus verifying retrograde movement of the AAV9 vector.”

Since Pompe disease is associated with tongue-related disorders such as dysarthria, dysphagia, and obstructive sleep apnea, specifically stimulating tongue motor output could be of great interest to treat these disorders in patients. 

Read more about the complications of Pompe disease

Here, researchers led by David D. Fuller, PhD, from the University of Florida in Gainesville demonstrated that lingual delivery of an AAV9 vector can drive the expression of DREADD in XII motor neurons.

“This approach provides a means to use ‘remote control’ to stimulate tongue motor activity in Pompe disease,” the researchers wrote. They added that this approach could “open new therapeutic opportunities for lingual-related dysfunction” in Pompe disease, as well as others.

The study is published in the Journal of Neurophysiology.

Pompe disease is a rare genetic disease caused by a mutation in the gene coding for the acid alpha-glucosidase (GAA) enzyme, the function of which is to break down glycogen to produce glucose. When the enzyme does not function properly due to a mutation, glycogen accumulates inside tissues, causing damage.

Reference

Singer ML, Rana S, Benevides ES, Barral BE, Byrne BJ, Fuller DD. Chemogenetic activation of hypoglossal motoneurons in a mouse model of Pompe disease. J Neurophysiol. Published online August 17, 2022. doi:10.1152/jn.00026.2022