Tag: nerve damage

Categories : New Compounds and Treatments Regenerative MedicineTags :

Researchers Identify New Compound that Could Stimulate Nerve Regeneration

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Research published in Nature has identified a new compound that can stimulate nerve regeneration after injury, as well as protect cardiac tissue from the sort of damage seen in heart attack. The UCL-led study identified a chemical compound, named ‘1938’, that activates the PI3K signalling pathway, and is involved in cell growth.

Results from this early research, which was done in partnership with the MRC Laboratory of Molecular Biology (MRC LMB) and AstraZeneca, showed the compound increased neuron growth in nerve cells, and in animal models, it reduced heart tissue damage after major trauma and regenerated lost motor function in a model of nerve injury.

Though further research is needed to translate these findings into the clinic, 1938 is one of just a few compounds in development that can promote nerve regeneration, for which there are currently no approved medicines.

Phosphoinositide 3-kinase (PI3K) is a type of enzyme that helps to control cell growth. It is active in various situations, such as initiating wound healing, but its functions can also be hijacked by cancer cells to allow them to proliferate. As a result, cancer drugs have been developed that inhibit PI3K to restrict tumour growth. But the clinical potential of activating the PI3K pathway remains underexplored.

Dr Roger Williams, a senior author of the study from the MRC Laboratory of Molecular Biology, said: “Kinases are ‘molecular machines’ that are key to controlling the activities of our cells, and they are targets for a wide range of drugs. Our aim was to find activators of one of these molecular machines, with the goal of making the machine work better. We found that we can directly activate a kinase with a small molecule to achieve therapeutic benefits in protecting hearts from injury and stimulating neural regeneration in animal studies.”

In this study, researchers from UCL and MRC LMB worked with researchers from AstraZeneca to screen thousands of molecules from its chemical compound library to create one that could activate the PI3K signalling pathway. They found that the compound named 1938 was able to activate PI3K reliably and its biological effect were assessed through experiments on cardiac tissue and nerve cells.

Researchers at UCL’s Hatter Cardiovascular Institute found that administering 1938 during the first 15 minutes of blood flow restoration following a heart attack provided substantial tissue protection in a preclinical model. Ordinarily, areas of dead tissue form when blood flow is restored that can lead to heart problems later in life.

When 1938 was added to lab-grown nerve cells, neuron growth was significantly increased. A rat model with a sciatic nerve injury was also tested, with delivery of 1938 to the injured nerve resulting in increased recovery in the hind leg muscle, indicative of nerve regeneration.

Senior author Professor James Phillips said: “There are currently no approved medicines to regenerate nerves, which can be damaged as a result of injury or disease, so there’s a huge unmet need. Our results show that there’s potential for drugs that activate PI3K to accelerate nerve regeneration and, crucially, localised delivery methods could avoid issues with off-target effects that have seen other compounds fail.”

Given the positive findings, the group is now working to develop new therapies for peripheral nerve damage, such as those sustained in serious hand and arm injuries. They are also exploring whether PI3K activators could be used to help treat damage in the central nervous system, for example due to spinal cord injury, stroke or neurodegenerative disease.

Source: University College London

Categories : Regenerative MedicineTags :

Scientists Coax CNS Axons into Regenerating

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Severed axons are unable to regenerate, which means that central nervous system (CNS) injuries such as to the spinal cord, can result in permanent loss of sensory and motor function. Presently, there are very limited options to help these patients regain their motor abilities. In mice, researchers have found that deleting a certain gene can cause axons to regrow. The results have recently been published in the scientific journal Neuron.

In a study using mice, a research team led by Associate Professor Kai Liu found that the deletion of PTPN2, a phosphatase-coding gene, in neurons can prompt axons to regrow. Combination with the type II interferon IFNγ, can accelerate the process and increase the number of axons regenerated.

Unlike the CNS, peripheral nerves have a greater ability to regrow and repair by themselves after injury. Scientists have yet to fully understand the relationship between this self-repair and the intrinsic immune mechanism of the nervous system. Thus, the team aimed to resolve how immune-related signalling pathways affected neurons after injury, and whether they could enhance axonal regeneration directly.

This study investigated whether the signalling pathway IFNγ-cGAS-STING had any role in the regeneration process of peripheral nerves. Researchers found that peripheral axons could directly modulate the immune response in their injured environment to promote self-repair after injury.

In previous research, Prof Liu’s team had already demonstrated that elevating the neuronal activity and regulating the neuronal glycerolipid metabolism pathway could  boost axon regenerative capacity. The current study is providing further insights into the search of treatment solutions for challenging conditions such as spinal cord injuries, with one possible option being the joining of several types of different signalling pathways.

Source: EurekAlert!

Categories : Regenerative MedicineTags :

Hydrogen Peroxide Clue to Repairing Nerve Damage

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A healthy neuron.
A healthy neuron. Credit: NIH

Zebrafish and human DNA are over 70% similar, and the fish is widely used for biomedical research, particularly in its capacity for appendage and nerve damage regeneration. Now, the researcher who discovered the role of hydrogen peroxide in these restorative processes delves deeper in a recent study published in the Proceedings of the National Academy of Science (PNAS).

In 2011, Dr Sandra Rieger made the groundbreaking discovery that hydrogen peroxide is produced in the epidermis and is responsible for promoting nerve regeneration following injury.

Dr Rieger stated, “It was a great discovery, but at the time we did not know the exact molecular mechanisms that drove nerve regeneration after injury.”

In her latest study, Rieger and her colleagues investigated how hydrogen peroxide stimulates nerve regeneration. They studied this process using time-lapse imaging with fluorescent labelling of proteins in zebrafish and mutant analysis.

“Time-lapse imaging provides a detailed view of the biological processes and relationships between nerves and skin, as well as how these interactions lead to regeneration,” explained Dr Rieger. “The findings we sought will answer the question of how the skin affects regeneration, as the skin is so important in producing factors that are essential to the regeneration process.”

Hydrogen peroxide was found to react to Epidermal Growth Factor Receptor (EGFR) in the skin, which is essential for skin remodelling and aids nerve regrowth into the wound. “This is vital for the restoration of the skin,” said Dr Rieger.

“However, we discovered that if hydrogen peroxide is not present in neurons, nerve endings also cannot regenerate,” Dr Rieger continued. “It appears that both neurons and skin require hydrogen peroxide to coordinate the regeneration of their nerve endings.”

It is hoped that these findings will pave the way for future studies that lead to improved therapies for restoring skin and nervous system functions.

Source: University of Miami