One molecule, two opposite effects
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Following a spinal cord injury, severed axons fail to reconnect. At first, because they age and lose the ability to regenerate. And second, because astrocytes in the environment in which they try to regrow build up a barrier that prevents neurons from moving further.
The molecule RhoA is involved in both mechanisms. Until recently only its effect on neurons was known. This knowledge prompted a clinical trial, published in 2018. The study with a medication targeting RhoA inhibition was unfortunately discontinued for lack of effect.
Tracing the effect
A group of scientists led by Frank Bradke recently published results that reveal why the clinical trial failed. By digging further into the mechanisms of RhoA activity, they found that its presence limits neuron regeneration as well as the environmental inhibition.
Releasing the right break
Knowing this, the researchers tested a more subtle approach. They managed to diminish RhoA only in neurons, while entirely avoiding the astrocytic one. This scenario, in which the brake is only released where needed could become a key factor for regeneration. Yet, the future will show if this approach is suitable on a cellular level in a clinical context.
This study was published in the journal Neuron and was supported by Wings for Life.
Source: Stern S, Hilton BJ, Burnside ER, Dupraz S, Handley EE, Gonyer JM, Brakebusch C, Bradke F. RhoA drives actin compaction to restrict axon regeneration and astrocyte reactivity after CNS injury. Neuron. 2021 Nov 3;109(21):3436-3455.e9. doi: 10.1016/j.neuron.2021.08.014. Epub 2021 Sep 10. PMID: 34508667.
You can find out more on the spinal cord and the influence of its damage on the human body in our basic-information. Wings for Life Glossary gives an understanding of scientific terms.