16 November 2021

The cure for paralysis

A research team from Northwestern University, USA, has developed a drug that triggers the regeneration and proliferation of nervous tissue in paralyzed animals with severe spinal cord lesions. Just four weeks after a single injection of the drug into the cerebrospinal fluid, the rodents regained the ability to walk. 

By sending bioactive signals to cells that trigger regeneration, the revolutionary therapy led to the restoration of severe spinal cord injuries in five ways: severed axons regenerated; the volume of scar tissue, which can mechanically interfere with regeneration, significantly decreased; myelin, necessary for the effective transmission of electrical impulses, is re-formed around damaged cells; functional blood vessels grow to deliver nutrients to cells at the site of injury; most of the motor neurons do not die. After the medicine has performed its functions, it begins to decompose into nutrients for cells and is completely eliminated from the body within 12 weeks without noticeable side effects.

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Life expectancy has not improved since the 80s

According to the National Spinal Cord Injury Statistical Center, there are currently about 300,000 people living with spinal cord injury in the United States. Less than 3% of people with a complete lesion ever recover basic physical functions. Approximately 30% are re-hospitalized at least once in any year after the injury. The life expectancy of people with spinal cord injuries is significantly lower than that of people without spinal cord injuries, and the situation has not improved since the 80s.

Currently, there is no therapy that triggers spinal cord regeneration. The research team has been working to change the outcomes of spinal cord injury, given the huge impact it can have on patients' lives. "Dancing molecules" hit moving targets

Receptors in neurons and other cells are constantly moving. The secret of the new therapeutic approach is to control the movement of molecules so that they can find and properly engage these receptors. Injected in liquid form, the drug immediately turns into a complex network of nanofibers that mimic the extracellular matrix of the spinal cord. By repeating the movement of biological molecules and including signals for receptors, synthetic materials are able to interact with cells. The main feature of the development is the simultaneous control of the movement of more than 100,000 molecules inside nanofibers. By constantly moving, dancing, or even temporarily jumping out of these structures, they are able to connect more effectively with the receptors.

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A longitudinal section of the spinal cord treated with a bioactive drug, 12 weeks after the injury. Blood vessels (red) regenerate in the lesion.

The team found that fine-tuning the movement of molecules in the nanofiber network, making them more flexible, led to greater therapeutic efficacy in paralyzed mice. It was also shown that the drug with enhanced molecular motion showed better results during experiments on human cells in vitro, indicating increased bioactivity.

In other words, molecules moving faster will encounter receptors more often than sluggish and less "social" ones that may never come into contact with cells.

One injection, two signals

After connecting to the receptors, the moving molecules trigger two cascading pathways, each of which is extremely important for spinal cord repair. One signaling pathway prompts the long processes of neurons in the spinal cord to regenerate. Like electrical cables, axons carry impulses between the brain and the rest of the body. The rupture or damage of axons can lead to loss of sensitivity in the body or even to paralysis.

The second signaling pathway helps neurons survive injury. It triggers the proliferation of other cell types, contributing to the restoration of lost blood vessels that feed neurons and other cells for tissue repair. The therapy also stimulates the restoration of myelin around axons and reduces the formation of glial scars, which act as a mechanical barrier preventing the healing of the spinal cord.

The synthetic materials used in the study mimic the natural proteins needed to induce the desired biological reactions. They are short modified peptides that, when joined by thousands, can survive for several weeks while maintaining bioactivity.

Universal application

The tissues of the central nervous system that have been successfully restored in the damaged spinal cord are similar to brain tissues affected by stroke and neurodegenerative diseases (amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease). The movement of molecules is a key factor in bioactivity, so it can form the basis of new treatments for these diseases.

The article by Z.Alvarez et al. Bioactive scaffolds with enhanced supramolecular motion promote recovery from spinal cord injury is published in the journal Science.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on the materials of Northwestern University: 'Dancing Molecules' Successfully Repair Severe Spinal Cord Injuries.


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