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New Drug Has Potential to Treat Neurological Disorders

by Ramya Rachamanti on August 29, 2019 at 4:05 PM
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New Drug Has Potential to Treat Neurological Disorders

New drug can prevent neuronal death by altering glucose metabolism in stressed neurons, according to a new study done on mice by the international team of scientists from Gero Discovery LLC, the Institute of Biomedical Research of Salamanca, and Nanosyn, Inc. The results are published in the Scientific Reports Journal.

Brain injuries of different nature and neurological disorders are among the most important causes of death worldwide. According to WHO, stroke is the second most common cause of mortality, and more than a third of people who have survived a stroke will have a severe disability.

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What is more, as the population ages, millions more people are posed to develop Alzheimer's or Parkinson's diseases in the near future. However, there are no efficient drugs for major neurodegenerative diseases. It is thus critically important to understand the biology of these diseases and to identify new drugs capable of improving quality of life, survival, and, in the best-case scenario, curing the disease completely.

Glycolysis is generally considered as the metabolic pathway essential for cell survival since it meets cell energy needs in case of intensive energy consumption. However, it is already known that in the brain tissue, the situation is quite different - different cell types show distinct glucose metabolism patterns.
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In neurons, only a small portion of glucose is consumed via the glycolysis pathway. At the same time, astrocytes provide nutrients to neurons and utilize glycolysis to metabolize glucose. These differences are mostly due to the special protein called PFKFB3, which is normally absent in neurons and is active in astrocytes.

In the case of certain neurological diseases, stroke being one of them, the amount of active PFKFB3 increases in neurons, which is highly stressful for these cells and leads to cell death.

An international team of researchers led by Peter Fedichev, a scientist and biotech entrepreneur from Gero Discovery, and professor Juan P. Bolaños from the University of Salamanca, suggested and further confirmed in the in vivo experiments that a small molecule, the inhibitor of PFKFB3, may prevent cell death in the case of ischemia injury.

Inhibition of PFKFB3 improves motor coordination of mice after stroke and reduced brain infarct volume. Moreover, in the experiments using mouse cell cultures, it was shown that PFKFB3 inhibitor protects neurons from the amyloid-beta peptide, the main component of the amyloid plaques found in the brains of Alzheimer's disease patients.

Professor Juan P. Bolaños: "Excitotoxicity is a hallmark of various neurological diseases, stroke being one of them. Our group has previously established a link between this pathological condition and high activity of PFKFB3 enzyme in neurons, which leads to severe oxidative stress and neuronal death"

"We are glad that our hypothesis that pharmacological inhibition of PFKFB3 can be beneficial in an excitotoxicity-related condition, such as stroke was confirmed. I would like to note that In our work, we used a known molecule to demonstrate that PFKFB3 blockage has a therapeutic effect. But, we have also performed the same experiments with other proprietary small molecule designed in our company and showed that it had a similar effect.

There is, of course, still much work to do. We are currently investigating the efficacy of our compounds in the models of orphan excitotoxicity-related neurological diseases. We have already obtained good safety results in mice and believe that we will be successful in our future investigations" said Olga Burmistrova, Director of preclinical development in Gero Discovery.

Gero Discovery team is planning to proceed with preclinical trials and to move into clinical trials soon. "These promising results bring hope to dozens of millions of patients suffering from life-threatening neurological diseases and provide tremendous business opportunities in many indications with unmet needs. We start communicating with potential investors and co-development partners and invite interested parties to collaborate on the further development of this breakthrough medicine through the preclinical and early clinical stage" mentioned Maksim Kholin, the Gero Discovery Co-Founder and Business Development Director.

Source: Eurekalert
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