Researchers of the Medical Research Council, UK, identified the efficacy of GSK2606414 compound in preventing the death of brain cells in mice which raise hope for Alzheimer’s patients, but they need to wait at least 10 years to get the benefits from this discovery.
Many experts in this field described GSK2606414 as a breakthrough in the research for the treatment of brain diseases as this compound was the first chemical to prevent neurodegeneration completely.
GSK2606414 was discovered by GlaxoSmithKline, and it was initially investigated for the treatment cancer but failed to show positive results.
Researchers noted that testing of this drug’s safety and efficacy in human clinical trials is the reason behind the delay.
In this preclinical study, scientists induced prion disease (a neurodegenerative disorder) in mice and divided them into two groups. In one group, the mice were injected with GSK2606414 into their stomach by using a mouth tube. Other groups were used as control.
The results showed that, the mice in the experimental group lived longer compared to mice in the control group. Additionally, mice in the treatment group retained their neuro-motor abilities when Reflex test was used. In contrast, mice in the control group failed the reflex test.
The study results also showed that mice that were treated with GSK2606414 had lost 20 percent of their body mass and experienced high levels of blood sugar. Both of these observed side effects revealed the effect of the drug on the pancreas.
GSK2606414 in prevention of brain death
In the instances of viral attack, accumulation proteins are observed in brain cells. As a part of the natural defense mechanism, the healthy brain cells respond by completely shutting down the protein production, to prevent the spread of the virus. This phenomenon is called as unfolded protein response (UPR).
However, in case of patients with neurodegenerative disease, the brain cells produce “misfolded” proteins. These faulty proteins overactivate the UPR and prevent its timely switch off. This leads to prolonged inactivation of protein synthesis, thereby creating scarcity of proteins necessary for the nerve cell survival.
Unavailability of these proteins will eventually result in brain cell death. This uncontrolled death of neurons in the brain further deteriorates the disease. An enzyme, Protein Kinase R (PKR)-like Endoplasmic Reticulum Kinase (PERK), was identified to play a critical role in up-regulation of UPR.
The investigational compound, GSK2606414, selectively inhibits this PERK enzyme and restarts the protein production. This preclinical study revealed that GSK2606414 was a highly potent neuroprotective agent.
In spite of associated toxicities like diabetes and weight loss, researchers are positive about the discovery.
The researchers agree that even if GSK2606414 failed in human trials, the identified molecular pathway in itself can emerge as a platform for new treatment options. An increased research focus on this pathway is anticipated.
Overall, this discovery has raised the hope for new treatment options in the field of neurodegenerative diseases, which are devoid of effective therapies.
Written by: Janet Grace Ortigas