Synthetic molecules repair mouse brain function lost to disease and injury
The brain is an incredibly complex network of connections, but in some neurological disorders those connections can be lost. Researchers from the UK, Germany and Japan have now created synthetic molecules that may be able to help patch them up, with tests in cultured cells and mice showing promise in treating disease and injury.
Spinal injuries can be extremely debilitating, with broken connections preventing signals from moving from the brain to nerves and muscles. Diseases like Alzheimer’s can also begin to destroy neurons and their connections, resulting in memory loss, disrupted communication and behavioral changes.
To search for potential treatments for these kinds of conditions, researchers on the new study looked to a group of proteins called synaptic organizers. These molecules help to link neurons across synapses, maintaining the nervous system’s many connections. The hope was that by mixing and matching useful properties of these proteins, the researchers could develop artificial synaptic organizers that could restore some of the connections lost to injury or disease.
We created a molecule that we believed would help repair or replace neuronal connections in a simple and efficient way
Eventually they eventually settled on a particular artificial molecule called CPTX, which worked very well in lab-grown cell cultures to organize connections between neurons.
“Damage in the brain or spinal cord often involves loss of neuronal connections in the first instance, which eventually leads to the death of neuronal cells,” says Radu Aricescu, an author of the study. “Prior to neuronal death, there is a window of opportunity when this process could be reversed in principle. We created a molecule that we believed would help repair or replace neuronal connections in a simple and efficient way.”
Next, the team tested the molecule in animals, injecting CPTX into the brains of mice with conditions like cerebellar ataxia, Alzheimer’s disease and spinal cord injuries. In all cases, they observed neuronal connections being restored, while the animals performed better on memory, coordination and movement tests. A single injection improved things for about a week in the ataxia model, and up to eight weeks in the mice with injured spinal cords.
The team says that they’re developing new versions of CPTX that may be more stable and effective. Hopefully, further work can investigate whether the results will carry across to humans as well.
The research was published in the journal Science.
Source: UK Medical Research Council