Jorge Pincay ‘20

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease that results in the degradation of nerve cells in the brain over time. This disease is the result of a DNA mutation — a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion– that occurs in the gene that encodes for the huntingtin (Htt) protein. This repeat expansion causes a highly toxic form of the Htt protein to flood the brain, leading to brain atrophy and deterioration of a person’s mental and physical abilities. Currently there are no treatments to reverse or slow down the progression of this disease. However, gene therapies aimed to increase the expression of neurotrophic factors in the central nervous system (CNS) are currently undergoing testing in transgenic HD mouse models. These neurotrophic factors play an essential role in the health of the CNS by promoting growth, development, survival, and plasticity of neurons associated with motor function. 

The current method for the delivery of this therapeutic is direct delivery. Neurotrophic factors encapsulated in a liposome complex are injected directly into the brain using a needle. However, the invasiveness of this procedure poses the risk of neurological damage, bleeding, and infection. A group of scientists from Chang Gung University and National Tsing Hua University recently developed a new, less invasive form of delivery of a neurotrophic factor called gilial cell line-derived neurotrophic factor (GDNF)  in order to avoid the risks associated with direct injection. This novel method involves the use of focused ultrasound (FUS) in the presence of microbubbles, small gas-filled bubbles that are injected intravenously, to open the blood-brain-barrier and effectively deliver GDNF. 

The results of this therapy, delivered by a combination of focused ultrasound and microbubbles have demonstrated the potential for this therapy to slow down or even reverse the effects of HD in transgenic mouse models. More specifically, the results of this therapy, delivered by ultrasound and microbubbles, have shown a decrease in the rates of apoptosis and oxidative stress along with increased protection of neurological cells. 

The positive effects of this study have shown that there is a possibility of applying  this form of therapy to human patients in the future. Furthermore, the results of this therapeutic administration have shown potential for revolutionary treatment of neurological disease.

Reference:

1. C. Lin, et al., Focused ultrasound-induced blood brain-barrier opening enhanced vascular permeability for GDNF delivery in Huntington’s disease mouse model. Brain Stimulation 12, 1143-1150 (2019). Doi:10.1016/j.brs.2019.04.011.
2. Image retrieved from: C. Lin, et al., Focused ultrasound-induced blood brain-barrier opening enhanced vascular permeability for GDNF delivery in Huntington’s disease mouse model. Brain Stimulation 12, 1143-1150 (2019). doi:10.1016/j.brs.2019.04.011