This week (19th Oct–24th October) is Real Time Chem Week (if that means nothing to you,check out their FAQ page here!). As part of it, we’re featuring the RTC Week competition-winning entries of five different chemists here on Compound Interest, with a different feature every day this week. Today’s feature takes a look at how deuterating fatty acids we normally consume in our diet could provide possible treatments for Parkinson’s and other nervous system diseases.
Maksim Fomich is currently looking into creating deuterated polyunsaturated fatty acid compounds, with a view to using them to potentially treat a range of diseases. Here, he explains the premise behind his research.
“My research concerns the synthesis of deuterium-reinforced polyunsaturated fatty acids (PUFAs).
Our initial hypothesis was based on the fact that substitution of some hydrogen atoms in PUFAs for deuterium might protect the most vulnerable sites of the molecule (the carbon carbon double bonds) from oxidation and degradation. Hydrogen atoms are composed of a proton and an electron; a deuterium atom is simply a hydrogen atom with an added neutron.
Unfortunately, it is not easy to substitute these atoms into natural PUFAs, so we needed to make these molecules from available compounds using a multistep synthesis. These and analogous acids (with different combinations of hydrogen and deuterium) not only help us to investigate the mechanism of lipid oxidation, but also allow us to test their protective properties in organisms. For example, tests on yeast showed that even small addition of deuterated PUFAs (up to 20 %) helped to suppress lipid auto-oxidation and prevent cell death under oxidative stress conditions.
Our major dream is to feed people with deuterated fats and see if they live longer. For that purpose, we would need a really big quantity of these expensive fats. Therefore, we put our major efforts into delivery of deuterated PUFAs to those places in human organism, which suffer from free radicals and which need this reinforcement mostly. These are the nervous system and eyes.
In the nervous system, oxidative damage of membrane PUFAs is suspected to play major role in Parkinson’s disease. Our group showed that a diet containing deuterated PUFAs diminished degeneration in a mouse model of Parkinson’s disease.
Also, the fact that deuterated PUFAs also protect mitochondria from oxidative stress suggests that deuterated PUFA can be used to treat mitochondrial disorders. Currently, our compounds are undergoing clinical trials on humans to treat another nervous system disorder, Friedreich’s ataxia.
Another hypothesis we are currently investigating is that deuterated PUFAs can be used for treatment of retinal diseases, as the reason for some of them could be continuous action of free radicals and destruction of membrane lipid compounds in the retina.”
- Isotopic reinforcement of PUFAs diminishes nigrostriatal degeneration in a mouse model of Parkinson’s disease (£) – M Shchepinov and others
- Small amounts of isotope-reinforced PUFAs suppress lipid auto-oxidation (£) – S Hill & others
- Isotope-reinforced PUFAs protect mitochondria from oxidative stress (£) – A Y Andreyev & others