Research finds target for central nervous system injury and neurodegenerative disease

Researchers in Birmingham in the UK have identified a potential drug target for treating long-term neurological conditions such as Alzheimer’s disease and promoting nerve regeneration in central nervous system injuries.

Research, published last week in science progressis part of a course of action that explores signaling pathways that respond to DNA damage, which is seen both in long-term neurological conditions and after traumatic injury, such as the spinal cord or optic nerve.

Regardless of the cause, neurons appear unable to fully repair this damage, and the cell’s DNA damage response (DDR) system is activated. Continuous activation of this system affects the function of the nervous system and potentially leads to programmed cell death (programmed cell death).

The same molecular factors

Zubair Ahmed from the University of Birmingham Institute of Inflammation and Agingand Richard Toxworth from Institute of Cancer and Genomicsto explain how this happens.

Ahmed said, “Our research began to explore DNA damage pathways that were activated after nerve injury. However, the same molecular factors in pathways appear in neurodegenerative diseases, and a full understanding of these mechanisms is an important step toward identifying potential targets for drug therapies.”

The latest research paper follows two recently published studies on spinal cord injury from the same research group. These studies showed that an existing drug may reduce damage after spinal cord injury, by Preventing the inflammatory response in the spinal cordThe brain-penetrating candidate drug currently being developed as a cancer treatment Promote nerve repair after injury.

gate guards

The current study focused on pathways involving enzymes called Checkpoint kinase 1 (Chk-1) and Checkpoint kinase 2 (Chk-2), which act as gatekeepers for the DDR system, and can be inhibited using small molecules called Checkpoint kinase (Chk) inhibitors. -he is).

The researchers first looked at a Drosophila model of amyloid toxicity, which occurs in neurological diseases when abnormal levels of this natural protein clump together and disrupt nerve cell function. Here the researchers found that reducing Chk1 or Chk2 expression has a protective effect.

They then turned their attention to investigating whether these findings could be reproduced in animal trauma models of optic nerve damage and spinal cord injury.

Optic nerve damage has been of interest to researchers because it occurs in patients with glaucoma, multiple sclerosis, Alzheimer’s disease and Parkinson’s disease. Animal models here showed that administration of Chk-2 promoted neuronal survival, and resulted in significant nerve regeneration while improving optic nerve function after injury.

A new treatment strategy

These findings were mirrored in spinal cord injury, where administration into the spinal canal promoted significant regrowth of neurons outside the injury site and, within three weeks, complete restoration of previously impaired sensation and movement.

Toxworth added: “This study raises the possibility of developing an entirely new treatment strategy for a variety of neurodegenerative diseases, which aims to support nervous system function and slow disease progression.”

The University of Birmingham Enterprise has filed patent applications covering the pathways and mechanisms disclosed in all three papers and is now seeking investment and partners for commercial development or licensing.