Applying gene therapy to correct brain defects


An article published in Brain by Wolfe, et al. described their advances in performing neural corrections in a large-brained model using gene therapy.

Gene therapy is a technique used to treat diseases by altering the patient’s genetic material, to either compensate for abnormal genes or create a beneficial protein. This is done by introducing genetic material into cells via an engineered ‘carrier’, known as a vector.

Source: National Human Genome Research Institute: Gene Therapy.  (2020)

Alpha-mannosidosis (AM) is a rare genetic disorder (1 in 500,000 people worldwide), caused by a mutation in a gene (MAN2B1) that codes for an enzyme working in the lysosomes. Lysosomes are cellular compartments that break up and digest materials. The enzyme assists in breaking down complex sugar molecules. In AM, this enzyme no longer functions, creating an accumulation of sugars in the lysosomes, causing cells to malfunction and die.

Source: Discover Alpha Mannosidosis, Mechanism of Disease. (2020)

AM is characterized by intellectual disability, a difficulty coordinating movements (ataxia), skeletal abnormalities and distinctive facial features.

In this study, researchers successfully corrected for this disease in animal models using gene therapy. They successfully did this in mice first, and then also in cats. Cats have a large brain (similar to humans) and are affected by AM in the same way, making their response especially important.

The vector was injected into the rodents and cats via the carotid artery and successfully crossed the blood-brain barrier. Several weeks after the vector was injected in the cats, the researchers found that the corrected gene had distributed to different parts of their brain, including the cerebellar cortex, hippocampus and mid-brain.

The treated cats had a delayed onset of neurological symptoms and a longer lifespan, and those treated with larger amounts lived the longest.  

Although this did not cure the disorder, it is the first time that the whole brain of a large-brained animal has been treated, and this is especially intriguing for its future clinical use in humans with this condition!

From: Brain (July 2020). Volume 143, Issue 7.
Authors: Sea Young Yoon, Jacqueline E Hunter, Sanjeev Chawla, Dana L Clarke, Caitlyn Molony, Patricia A O’Donnell, Jessica H Bagel, Manoj Kumar, Harish Poptani, Charles H Vite and John H Wolfe.

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