What are those wonky line drawings to the left, you ask? They are visual representations of four molecules that Professor Richard Deth (rhymes with teeth) and his grad student, Malav Trivedi, think might hold the key to autism.
The one on the far left you’re probably familiar with…although hopefully not too familiar. BCM-7 is a peptide (or piece of protein) that is generated when the milk protein casein gets digested. As you can see, the version found in cow’s milk looks a bit different from the one found in human milk. α-Gliadin-7 is a peptide that results from gluten protein digestion.
Now, I’ve always been one to steer clear of gluten and dairy free diet plans. I’m something of bread and butter fiend and the thought of eliminating either from my diet, even if it did make my gut feel better, well…it would make my heart cry a little.
My personal gastrointestinal preferences aside, so-called “GFCF” diets (for Gluten Free — Casein Free) are being adopted by many families with autistic children. Despite the fact that no statistical evidence has confirmed a connection between gluten or casein and autism, many parents say they notice improvements in their children’s symptoms when they eliminate gluten and dairy from the menu.
Deth has long considered autism to be a result of oxidative stress in the body. While not the mainstream scientific opinion, Deth’s hypothesis is shared by others in the field. “If oxidative stress is true,” he said, “perhaps the GF/CF diet improves things.”
As we talked he pulled out a diagram to keep me oriented. The first time I looked at this kind of diagram I cried (I don’t mean metaphorically. I really started crying. And then I dropped out of my cell biology class.) So, if this stresses you out half as much as it did the 18 year old me, don’t worry.
Basically that mess up there highlights a series of biological pathways that have to do with oxidative stress. And what does that mean exactly? Basically it’s a state in which a cell has too many reactive oxygen species floating around. ROSs as they’re called (not to be confused with ROUSs), are molecules that contain oxygen and are ready to go at it with other crucial molecules in the body. Up there in the top right quadrant of the jumble, you’ll see “GSH” or glutathione. This puppy is the holy grail when it comes to getting rid of ROSs. If anything gets in the way of GSH’s ability to do it’s job, well…oxidative stress persists.
The GSH protein contains a whole bunch of the amino acid cysteine in its structure. So as you can imagine, proper functioning of GSH depends on getting enough cysteine into cell. Trivedi’s RISE:2012 work demonstrated that the gluten– and casein– derived peptides shown at the top inhibit cysteine uptake in cells from the human intestinal lining. Interestingly, the effect was similar to that of morphine and when they blocked opiate receptors with another molecule, the peptides no longer got in the way of cysteine uptake.
The peptides also impact another part of the diagram above. See where it says “methylation reactions”? Methylation is a process that turns genes on or off based on both inherited and environmental factors. It is one of a few biological processes collectively called “epigenetics,” which is any kind of gene regulation that happens outside of the original sequence we’re born with. Trivedi showed that methylation increased when both human and bovine BCM-7 entered the picture. Gene expression, on the other hand went down in the case of the bovine peptide and up in the human case. All of this indicates that there may be a link between the peptides, epigenetics, and the oxidative state of the cell.
While still very early data, these results could lend insight into the broader biological mechanism of autism spectrum disorders.