Penetrates and heals
A research team from the University of Birmingham has demonstrated on cell lines and animal models that the candidate drug AZD1390 can block the reaction to DNA damage in nerve cells and promote the regeneration of damaged nerves, leading to the restoration of their motor and sensory functions after spinal injury. A few weeks ago, the same research team showed that another investigational drug (AZD1236) can reduce damage after spinal cord injury by blocking the inflammatory response. Both studies were supported The AstraZeneca Open Innovation Program.
AZD1390 is a highly selective inhibitor of the ataxia telangiectasia mutated protein (ATM) mutant in ataxia telangiectasia and is currently being investigated for blocking ATM-dependent signaling and repair of double-stranded DNA breaks to increase the sensitivity of cancer cells to radiation therapy.
The DNA damage response system is activated by a violation of DNA integrity, including double-stranded breaks that occur in several common cancers, as well as after spinal cord injury. The researchers suggested that the constant activation of the DNA damage response system may hinder recovery after spinal cord injury and that its blocking will contribute to the restoration of nerves and their functions after injury. Initially, they showed that AZD1390 stimulates the growth of nerve cells in culture and inhibits the ATM protein kinase pathway, a biochemical cascade that regulates the response to DNA damage.
The researchers then used animal models to study in vivo the effect of AZD1390 on spinal cord injury. They showed that when administered orally, AZD1390 penetrates the blood-brain barrier and causes significant suppression of the ATM protein kinase pathway, leading to regeneration and restoration of the ability of nerves to transmit electrical signals through the site of injury. The animals treated with AZD1390 demonstrated recovery of motor and sensory functions, and 4 weeks after the injury were no different from healthy relatives.
The simple method of oral administration and a good safety profile suggest that AZD1390 is a potential new therapy that promotes the restoration of function after spinal cord injury in patients.
The researchers have applied for a patent.
Article by Z.Ahmed et al. The brain-penetrant ATM inhibitor, AZD1390, promotes axon regeneration and functional recovery in preclinical models of spinal cord injury published in the journal Clinical and Translational Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Birmingham: Research shows investigational drug fosters nerve repair after injury.