Injection of "dancing molecules" gets paralyzed mice walking in 4 weeks
Spinal cord injuries are among the most debilitating, leading to difficulty walking or a complete paralysis of limbs. In a new breakthrough study, researchers at Northwestern University have developed a gel containing “dancing molecules” that allowed paralyzed mice to walk again four weeks after a single injection.
Neurons in the spine transmit signals between the brain and muscles, so damage to these can make even simple movements difficult or impossible. To make matters worse, the central nervous system has very limited capacity to repair itself, meaning paralysis is often permanent.
The new study reports a breakthrough therapy which, the team says, was able to repair the damage in five main ways. It regenerated axons, significantly reduced scar tissue formation, replenished the insulating myelin layer around axons, increased production of blood vessels, and increased the number of motor neurons that survived the injury.
In tests in mice, the results were very promising. The treatment was administered as a single injection of a liquid containing two types of modified peptides, and just four weeks later paralyzed mice were able to walk again.
The team says that the treatment works because these peptides trigger cascading signals that help repair the spinal cord. One peptide sets off a signal that regenerates axons, while the second reduces scarring and promotes the regrowth of blood vessels and myelin.
After injection, the liquid gels into a nanofiber structure that mimics the extracellular matrix surrounding the spinal cord. That allows the peptides to stick around much longer to do their work, before the gel biodegrades after about 12 weeks.
“The signals used in the study mimic the natural proteins that are needed to induce the desired biological responses,” says Zaida Álvarez, first author of the study. “However, proteins have extremely short half-lives and are expensive to produce. Our synthetic signals are short, modified peptides that – when bonded together by the thousands – will survive for weeks to deliver bioactivity. The end result is a therapy that is less expensive to produce and lasts much longer.”
But the key breakthrough, the team says, is that the gel matrix allows the molecules to move around to find the right receptors in the cells. Intriguingly, the treatment showed greater efficacy in mice that received treatments with more mobile molecules. Similar results were seen in human cells in culture.
“Receptors in neurons and other cells constantly move around,” says Samuel Stupp, lead author of the study. “The key innovation in our research, which has never been done before, is to control the collective motion of more than 100,000 molecules within our nanofibers. By making the molecules move, ‘dance’ or even leap temporarily out of these structures, known as supramolecular polymers, they are able to connect more effectively with receptors.”
The team says that the therapy could initially be used to prevent paralysis in patients after major trauma, such as falls, sporting injuries or traffic accidents. It could also be applied to a range of other diseases.
“The central nervous system tissues we have successfully regenerated in the injured spinal cord are similar to those in the brain affected by stroke and neurodegenerative diseases, such as ALS, Parkinson’s disease and Alzheimer’s disease,” says Stupp. “Beyond that, our fundamental discovery about controlling the motion of molecular assemblies to enhance cell signaling could be applied universally across biomedical targets.”
The researchers say that they are already planning to present the new treatment to the FDA to begin the process of approval for human use.
The research was published in the journal Science. The team describes the work in the video below.
Source: Northwestern University