Glaucoma is a disease associated with elevated eye pressure that can damage the optic nerve and even lead to blindness. Although it shows some familiarity, it is not considered a genetic disease, yet the use of gene therapy could improve the course of the disease. This is discussed today on the pages of Science Advances, where a group of researchers from the University of Cambridge (United Kingdom) presents its idea to use gene therapy against neurodegenerative diseases, but not to correct the origin of a genetic defect, but to correct functional damage. Acting on several fronts. We’re talking about very preliminary studies, with evidence gathered in animal models, but that’s what it is.
The idea behind traditional gene therapy is to correct a gene defect by introducing from the outside the working copy of the defective gene (or a system capable of repairing it, with the advent of genome editing). This is an innovative approach, even if it has been under study for years, especially designed for genetic diseases due to the alteration of a single gene. Yet, other fields of application for gene therapy could be on the horizon.
Gene therapy is not new to neurological diseases, writes the team of Tasneem Khatib of the University of Cambridge, citing cases of Leber’s congenital amaurosis or spinal muscular atrophy. Disease, the latter for which AIFA has just approved the reimbursement of gene therapies for children weighing less than 13.5 kg. In both cases, these are therapies that work by trying to restore the lost and compromised function of a gene by providing a functioning copy. Khatib and colleagues went further: they tried to understand if gene therapy could repair a functional defect common to some neurodegenerative diseases, such as the failure of a part of neurons: the axons.
Axons are extensions of neurons along which nerve stimuli travel. If the axons do not work then, the neuronal communication suffers. And there are several pathologies in which axonal damage is found. Such as glaucoma and forms of taupathias, conditions associated with the accumulation of insoluble aggregates of a protein (the tau protein), which can be found in dementias, such as Alzheimer’s. Some evidence suggests that it is possible to improve axonal transport by stimulating axon growth and development. Like? By boosting the activity of two proteins, the researchers explain. In this case, strengthening means supplying the proteins in question from the outside: the brain-derived neurotrophic factor (BDNF) and its TrkB receptor (tropomyosin receptor kinase B).
To do this, the researchers resorted to gene therapy, exploiting a single viral vector to carry the information for the coding of both proteins in some animal models (mice and rats) of glaucoma and taupathy (classical gene therapy in fact makes use of viral vectors as a vehicle for gene information to be transported into host cells). In this way, they write, it is possible to achieve long-term expression of both proteins in target cells. “Instead of using a standard gene therapy approach whereby damaged genes are replaced or repaired, we used the technique to supply the brain with these molecules,” Khatib remarked, underlining the innovative nature of their approach.
Scientists have shown that their administration can improve axonal nerve impulse transport in animal models of disease (in detail, the researchers used a colored tracer to observe this transport between the retina and the brain), although the mechanisms by which two proteins manage to do this are not fully known, they explain. But not only: some clues, obtained by observing the behavior of animals used as a model of dementia and their tendency to explore new or already seen objects inside a maze, suggest that gene therapy is associated with an improvement in short-term memory. term.
The results observed in the visual pathways suggest that similar interventions, to improve axonal transport thanks to gene therapy, can also be achieved elsewhere in the central nervous system. And – the authors conclude – they open the way to new possible therapeutic strategies to repair the damage that characterizes some neurodegenerative diseases.
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