University of Szeged Leads in mRNA-Based Spinal Injury Treatment

Hungary Today 2024.12.04.

A new mRNA-based therapy for spinal cord injuries is being developed at the University of Szeged (SZTE) under the leadership of Professor Antal Nógrádi, and after promising studies on rodents, interventions are now being planned to treat dogs, reports Magyar Nemzet.

The Department of Anatomy, Histology and Embryology of the University of Szeged started investigating the possibility of treating damaged motor neurons in the 2000s. In 2007, stem cell therapy experiments were launched,

during which it was discovered that stem cells implanted in the area of the injury produced a mixture of four to five proteins, called secretome, which had a positive effect on the survival of damaged neurons.

Fact

A spinal cord injury involves damage to the spinal cord or the nerves at its end, called the cauda equina. Since the spinal cord transmits signals between the brain and the body, such injuries often result in lasting changes to strength, sensation, and bodily functions below the affected area. Beyond physical effects, individuals may face mental, emotional, and social challenges. While there is no definitive cure, ongoing global research offers hope for future breakthroughs in spinal cord repair. Meanwhile, current treatments and rehabilitation help many lead independent, fulfilling lives.

In 2019, the researchers started a collaboration with Norbert Pardi from the University of Pennsylvania to develop a way to deliver mRNAs encoding the components of the secretome to the site of injury, the spinal cord, so that the body can produce the proteins locally.

First, they tried to deliver a simple signalling protein, mRNA encoding green fluorescent protein, into the spinal cord wrapped in a lipid envelope, and then, after this was successful, they tried to deliver a therapeutic protein, mRNA encoding interleukin 10 (IL-10, an anti-inflammatory cytokine).
Studies have shown that 60 percent of the secretome’s effect is due to this protein, protecting nerve cells and reducing inflammation.
The next step was the introduction of mRNA encoding a protein that promotes the growth of axons and nerve cell extensions of surviving and damaged neurons, glial cell line-derived neurotrophic factor (GDNF).

The bruised cavity in the spinal cord at the site of the injury is small, only a few microliters in volume, less than the size of a droplet. Only the amount of material that does not cause major damage and does not dilate the cavity should be introduced. Injecting all four factors of the secretion already pushes this limit.

Therefore, researchers use so-called “cargo” cells for the therapy. The cargo cells are a group of white blood cells called macrophages, responsible for clearing foreign elements after injury.

These cells go to the site of spinal cord injury and carry with them the therapeutic proteins, which have been produced from the mRNAs they have injected.

The researchers plan to test the viability of the solution in larger animals after rodent models. Dogs would be an excellent model for this, as some breeds, such as dachshunds, are susceptible to diseases of the spine as a supporting structure due to their body structure. In diseased individuals, too long of a load-bearing arc can no longer be sustained by the spine and it will snap, causing damage to the spinal cord. The idea is to treat sick animals by stimulating macrophage production of IL-10.

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Via Magyar Nemzet; Featured image via Pixabay