spinal cord injuries

Innovative Nanogel Shown Effective in Treating Spinal Cord Injuries

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A recent study has introduced an innovative nanogel capable of delivering anti-inflammatory drugs directly to glial cells, showing promise in treating spinal cord injuries that lead to paraplegia or quadriplegia.

Innovative nanogels developed by researchers have shown effectiveness in targeting glial cells for the treatment of spinal cord injuries, offering a new avenue for therapeutic intervention.

In a study published in Advanced Materials, researchers Pietro Veglianese, Valeria Veneruso, and Emilia Petillo from Istituto di Ricerche Farmacologiche Mario Negri IRCCS in collaboration with Filippo Rossi of the Politecnico di Milano have demonstrated that an innovative nanovector (nanogel), which they developed, is able to deliver anti-inflammatory drugs in a targeted manner into glial cells actively involved in the evolution of spinal cord injury, a condition that leads to paraplegia or quadriplegia.

Challenges in Current Treatment Approaches

Treatments currently available to modulate the inflammatory response mediated by the component that controls the brain’s internal environment after acute spinal cord injury showed limited efficacy. This is also due to the lack of a therapeutic approach that can selectively act on microglial and astrocytic cells.

Nanogel – Scheme of selective drug treatment in the central nervous system. Credit: Politecnico di Milano – Istituto Mario Negri

Nanogel Development and Efficacy

The nanovectors developed by Politecnico di Milano, called nanogels, consist of polymers that can bind to specific target molecules. In this case, the nanogels were designed to bind to glial cells, which are crucial in the inflammatory response following acute spinal cord injury.

The collaboration between Istituto di Ricerche Farmacologiche Mario Negri IRCCS and Politecnico di Milano showed that nanogels, loaded with a drug with anti-inflammatory action (rolipram), were able to convert glial cells from a damaging to a protective state, actively contributing to the recovery of injured tissue.

Nanogels were shown to have a selective effect on glial cells, releasing the drug in a targeted manner, maximizing its effect, and reducing possible side effects.

Insights and Future Directions

“The key to the research was understanding the functional groups that can selectively target nanogels within specific cell populations,” explains Filippo Rossi, professor at the Department of Chemistry, Materials and Chemical Engineering ‘Giulio Natta’ at Politecnico di Milano. “This makes it possible to optimize drug treatments by reducing unwanted effects.”

“The results of the study,” continues Pietro Veglianese, Head of the Acute Spinal Trauma and Regeneration Unit, Department of Neuroscience at Istituto Mario Negri, “show that nanogels reduced inflammation and improved recovery capacity in animal models with spinal cord injury, partially restoring motor function. These results open the way to new therapeutic possibilities for myelolysis patients. Moreover, this approach may also be beneficial for treating neurodegenerative diseases such as Alzheimer’s, in which inflammation and glial cells play a significant role.”

Gene Therapy Shows Promise in Treating Neuropathy From Spinal Cord Injuries

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Summary: Gene therapy that inhibits targeted nerve cell signals effectively improves symptoms of neuropathic pain without negative side effects in mouse models of spinal cord injury or peripheral nerve damage.

Source: UCSD

An international team of researchers, led by scientists at University of California San Diego School of Medicine, report that a gene therapy that inhibits targeted nerve cell signaling effectively reduced neuropathic pain with no detectable side effects in mice with spinal cord or peripheral nerve injuries.

The findings, published in the May 5, 2022 online issue of Molecular Therapy, represent a potential new treatment approach for a condition that may affect more than half of patients who suffer spinal cord injuries. Neuropathy involves damage or dysfunction in nerves elsewhere in the body, typically resulting in chronic or debilitating numbness, tingling, muscle weakness and pain.

There are no singularly effective remedies for neuropathy. Pharmaceutical therapies, for example, often require complex, continuous delivery of drugs and are associated with undesirable side effects, such as sedation and motor weakness. Opioids can be effective, but can also lead to increased tolerance and risk of misuse or abuse.

Because physicians and researchers are able to pinpoint the precise location of a spinal cord injury and origin of neuropathic pain, there has been much effort to develop treatments that selectively target impaired or damaged neurons in the affected spinal segments. 

In recent years, gene therapy has proven an increasingly attractive possibility. In the latest study, researchers injected a harmless adeno-associated virus carrying a pair of transgenes that encode for gamma-aminobutyric acid or GABA into mice with sciatic nerve injuries and consequential neuropathic pain. GABA is a neurotransmitter that blocks impulses between nerve cells; in this case, pain signals.

The delivery and expression of the transgenes — GAD65 and VGAT — was restricted to the area of sciatic nerve injury in the mice and, as a result, there were no detectable side effects, such as motor weakness or loss of normal sensation. The production of GABA by the transgenes resulted in measurable inhibition of pain-signaling neurons in the mice, which persisted for at least 2.5 months after treatment. 

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There are no singularly effective remedies for neuropathy. Image is in the public domain

“One of the prerequisites of a clinically acceptable antinociceptive (pain-blocking) therapy is minimal or no side effects like muscle weakness, general sedation or development of tolerance for the treatment,” said senior author Martin Marsala, MD, professor in the Department of Anesthesiology in the UC San Diego School of Medicine. 

“A single treatment invention that provides long-lasting therapeutic effect is also highly desirable. These finding suggest a path forward on both.”

Potential target for restoring ejaculation in men with spinal cord injuries or ejaculatory disorders

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Potential target for restoring ejaculation in men with spinal cord injuries or ejaculatory disorders
New research provides insights on how to restore the ability to ejaculate in men who are not able to do so. Credit: Annals of Neurology

New research provides insights on how to restore the ability to ejaculate in men who are not able to do so.

In humans, the crucial role of the  in controlling ejaculation is based within a group of neurons located in the L3-L5 segments. In patients with a spinal cord lesion, the intactness of the L3-L5 segments was a determining factor for inducing ejaculation. Therefore, targeting this region might be a promising strategy for the recovery of ejaculation after spinal cord injury.

“The existence of a spinal ejaculation generator in the lumbar spinal cord of men was concluded from neuro-histological investigations and clinical observations from spinal cord injured patients. This generator is a promising therapeutic target for spinal cord injury  unable to ejaculate, and for other ejaculatory disorders,” said Dr. Francois Giuliano, senior author of the Annals of Neurology study.

Flexible Spinal Implant May Be Future Of Paralysis Treatment; Helps Paralyzed Rats Walk Again

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Although any kind of injury is bad, spinal cord injuries (SCI) might just be the scariest. Our spines are an information superhighway for nerves and their signals, which travel to the rest of the body. Just one strong blow to the back can be enough to offset vertebrae, which can tear or push into the spinal cord tissue, and just like that a person can be left paralyzed. It’s estimated that about 12,500 people will have a SCI each year, and 41 percent of them will end up either paralyzed from the waist down or throughout. After years of research, however, Swiss scientists are finally on track to giving these people their lives of movement back, with the help of elastic electrical spinal implants.

E-Dura

Scientists at Ecole Polytechnique Fédérale de Lausanne (EPFL) in Switzerland have been working on spinal cord implants for quite some time now, but a major roadblock for them has been maintaining flexibility akin to the spine. Current iterations of spinal cord implants are rigid and unable to move around if, for example, you’re bending down to tie your shoe. Over the course of a few days, these implants begin to rub against spinal tissue, causing inflammation and scar tissue build up. Eventually, the body rejects the implant.

The team’s new implant is called e-Dura. It’s named after the dura mater — one layer of the protective membrane that surrounds the spinal cord and brain — under which it’s placed. By using elastic silicone and cracked gold wiring, which created a mesh-like structure, the researchers were able to give it flexibility comparable to that of the nerve tissue surrounding it. And after two months of having the implant in their spines, paralyzed rats were able to walk, run, and jump without damage or rejection.

“This is quite remarkable. Until now, the most advanced prostheses in intimate contact with the spinal cord caused quite substantial damage to tissue in just one week due to their stiffness,” Dr. Dusko Ilic, from King’s College London, told the BBC. He was not involved in the study. “The work described here is a groundbreaking achievement of technology, which could open a door to a new era in treatment of neuronal damage.”

For the study, the researchers first tested the e-Dura against a stiffer implant and surgery alone, and found it was safe for the rats’ bodies without any adverse reactions. Then they inserted the implant in the rats’ motor cortexes to determine which signals indicated an intention to move their legs, and found that the device could indeed read signals, Live Sciencereported. Finally, they tested the device again on a group of paralyzed rats, finding that they had the ability to walk again after eight weeks, albeit with the help of an external stimulator which connected to the device with wires.

The team still has a long way to go if they want to bring this technology to humans. One of the first things they need to work on is getting the device to work independently of an external stimulator, which provides the signals for movement. “Translation of experimental treatments to humans often falters because insufficient attention is given to some of the more pragmatic aspects of translational science,” Dr. Mark Bacon, scientific director of the UK charity Spinal Research who wasn’t involved in the study, told the BBC.  “The combination of electrical and chemical stimulation has been proven in principle — in animal models at least — so it is encouraging to see the application of multidisciplinary efforts to take this one step closer to safe testing in patients.”

Source: Minev I, Musienko P, Lacour S, et al. Electronic dura mater for long-term multimodal neural interfaces. Science. 2014.