Researchers have found a cure for some disorders, such as spinal muscular atrophy, the target of Novartis’ Zolgensma by replacing the single or faulty gene. Most of the neurodegenerative disorders are caused by multiple genetic abnormalities, which makes them difficult to address with gene therapy targeted at single mutations. The study was published in Science Advances.
The Scientists from the University of Cambridge have chosen a different path. They divided not to go after the dysfunctional genes but they developed a gene therapy that expresses two therapeutic proteins that boost nerve development and function. The therapy was the target of Astellas’ acquisition of U.K. gene therapy biotech Quethera in 2018.
Brain-derived neurotrophic factor and its receptor tropomyosin receptor kinase are known to promote a process called axonal transport, in which axons help move mitochondria, lipids, proteins, and other key elements between neuronal cells. This machinery is crucial for the function and survival of nerve cells, and its disruption is a hallmark of neurodegenerative disease.
The team first tested the theory in a mouse model of glaucoma, a disease that causes the optic nerve to degenerate. Brain-derived neurotrophic factor and tropomyosin receptor kinase signaling has shown to protect neurons after optic nerve injury and to delay retinal degeneration.Delivery of the BDNF-TrkB gene therapy led to an increase in axonal transport in the optic nerves. The rodents’ retinas also showed an improved electrical response to light, which the researchers characterized as functional recovery.