Medical

Injection of "dancing molecules" gets paralyzed mice walking in 4 weeks

Injection of "dancing molecule...
A molecular model of the new injectable nanofiber matrix containing clusters of two peptides (green and orange), which trigger cascading signals to repair spinal cord damage
A molecular model of the new injectable nanofiber matrix containing clusters of two peptides (green and orange), which trigger cascading signals to repair spinal cord damage
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A molecular model of the new injectable nanofiber matrix containing clusters of two peptides (green and orange), which trigger cascading signals to repair spinal cord damage
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A molecular model of the new injectable nanofiber matrix containing clusters of two peptides (green and orange), which trigger cascading signals to repair spinal cord damage

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.

Severe spinal cord injuries repaired with 'dancing molecules'

Source: Northwestern University

6 comments
6 comments
HenkSmit
Perhaps grinding a pure nerve and injecting this porridge into the damage also helps to restore the nerve
Karmudjun
Thanks Michael - nice write up.

This is certainly a field rife with research. The hope of a breakthrough in the 1980's (remember 40 years ago?) revolved around a class of drugs labeled "Lazarovs", a name much hyped for a less than useful drug. The hopes were that an injection of a "Lazarov" into the spinal fluid could stabilize the damage and promote a rapid regrowth of the damaged axons. For those who like to focus on the failures - the Lazarov research explored many of the mechanisms of injury that these dancing peptides seem to impact! So 40 years of research dead-ends may have contributed to this possible breakthrough. The research on mRNA is slightly newer - and look at the international benefit those 'designer drugs' are providing!

The problem for humankind is the rigorous studies necessary to determine possible side effects, possible harms, and understand the mechanisms of action for both.
BlueOak
“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.”

Talk and mice experiments are cheap. But if they can make this work on humans, wow, a lot bigger than enabling paralyzed folks walk again!
dean27
This could be a great asset in treating IVDD patients.
byrneheart
Wow, the strain taken off patients, carers and health systems, given the labour and administrative intensive nature of care for spinal cord injuries, would be immense if this scales up. Perhaps no hope offered up for existing injuries, but looking forward is a very hopeful sign
guzmanchinky
It is 2021, I am sure hoping the next decade sees huge strides in these kinds of advances. Burn injuries and nerve damage are possibly the two most devastating trauma that can happen to someone...