Treatment of neurological diseases: study finds potential target

Researchers in Birmingham, UK, have identified a potential drug target to treat long-term neurological diseases such as Alzheimer’s disease and stimulate nerve regeneration in central nervous system injuries.

A study published last week in the Achievements of scienceis part of a work stream studying the signaling pathways that respond to DNA damage as observed in long-term neurological conditions and after a traumatic injury, such as to the spinal cord or optic nerve.

Regardless of the cause, nerve cells seem unable to fully repair this damage, and the cellular DNA damage response (DDR) system is activated. Constant activation of this system affects the functioning of the nervous system and potentially causes programmed cell death (apoptosis).

The same molecular factors

Zubair Ahmed from the University of Birmingham Institute of Inflammation and Agingand Richard Tuxworth of Institute of Cancer and Genomic Sciencesdecided to explain how it happens.

Ahmed said: “Our research started by looking at the DNA damage pathways activated after nerve damage. However, the same molecular factors of particularity in the pathways are seen in the neurodegenerative diseasesand a complete understanding of these mechanisms is an important step toward identifying potential targets for drug treatment.”

The latest research paper follows on from two recently published spinal cord injury studies conducted by the same research team. These studies have shown that an existing drug can reduce damage after spinal cord injury blocking the inflammatory response in the spinal cordand drug candidates that penetrate the brain are currently being developed as cancer therapies promotes nerve recovery after injury.


Current research focuses on pathways involving enzymes called Checkpoint kinase 1 (Chk-1) and Checkpoint kinase 2 (Chk-2), which act as gatekeepers of the DDR system and can be inhibited by small molecules called Checkpoint kinase inhibitors (Chk – there is).

For the first time, researchers have looked at a fruit fly model of amyloid toxicity, which occurs in neurological diseases when abnormal levels of this naturally occurring protein clump together and disrupt nerve cell function. Here, the researchers found that reducing Chk1 or Chk2 expression had a protective effect.

They then turned their attention to whether these findings could be replicated in animal models of neurotrauma involving optic nerve damage and spinal cord injury.

Optic nerve damage was of interest to researchers because it occurs in patients with glaucoma, multiple sclerosis, Alzheimer’s disease and Parkinson’s disease. Here, animal models showed that administration of Chk-2is promoted nerve cell survival and resulted in significant nerve regeneration with improved optic nerve function after injury.

A new strategy for the treatment of neurological diseases

These results were mirrored in spinal cord injury, where spinal canal administration promoted significant nerve cell growth beyond the injury site and, three weeks later, full recovery of previously impaired sensation and movement.

Tuxworth added: “This study raises the possibility of an entirely new treatment strategy for various neurodegenerative diseases that aims to support nervous system function and slow disease progression.”

University of Birmingham Enterprise has filed patent applications covering the pathways and mechanisms revealed in all three research papers and is now seeking investment and partners for commercial development or licensing. Treatment of neurological diseases: study finds potential target

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