By John Hewitt on July 30, 2014 at 3:17 pm
Stem cell technology can not come soon enough. Transplants of cells engineered to shuttle lifesaving medicines and the genes of youth may now be as coveted as Gollum’s golden ring, but the most precious cargo they might carry is something else entirely. The company that aims to bring us this new power is called Biplastiq, and their magic ingredient is a bit of fancy genetic reprogramming which allows mitochondria to be controlled with light.
Recently, it was announced that regulations for mitochondrial replacement to create so-called three-parent embryos will be put before the British Parliament. This technology would replace the faulty mitochondria inside an egg with healthy ones from a donor so that mothers with genetic preconditions could have healthy children. By contrast, Biplastiq aims to replace normal mitochondria with genetically-enhanced mitochondria that contain a protein that augments their function when illuminated. Previous research has demonstrated that free mitochondria can be coaxed into producing more energy in the form of ATP by low level light therapy (LLLT). This effect presumably occurs by altering the function of essential protein in mitochondria known as cytochrome c oxidase.
Taking a cue from this natural effect, researchers sought to magnify it, and make it more reliable. One issue regarding the absorption of light by cytochrome c, is that it changes depending on the chemical state (oxidation state) of the iron and copper atoms contained at its core. Last year, researchers were able to transfect a bacterially-derived, light-activated protein (known as delta rhodopsin) into mitochondria, and use it to directly control the electrochemical potential across their membranes. Essentially what they did is enhance the “proton motive force” to produce additional energy in the same way that chloroplasts do in plants.
What good is this for humans?
Recently we described new research aimed at helping veterans with traumatic brain injury. Perhaps even more insidious than these assaults is the suite of symptoms that falls under the blanket malady of Gulf War Syndrome. During that time many soldiers were tasked with disposing of chemical nasties in the desert, not to mention also having to breathe acrid smoke from nearby burning oil wells. Added to that toxic background, he likely was battling an internal antibody storm created by having to juggle vaccinations against everything from anthrax to botulism. The common theme most readily identifiable in this multifarious state seems to be poorly performing mitochondria.
Whether we call it mitochondrial disease, dysfunction, or disorder, one thing for sure is that it affects a lot of people. These illnesses can not usually be diagnosed with simple genetic tests. Typically doctors try to measure them using metabolic tests to gauge levels of critical enzymes in the blood. Unfortunately these methods are often imprecise and there is much confusion in the field. The high profile case of medical prisoner Justina Pelletier has given much publicity to the cause with news of her recent release from a Boston hospital. In her case, doctors at odds with each other ultimately turned against Justina’s family with the law on their side in a shocking abuse of medical and legal power.
Justina’s disease, and Gulf War Syndrome, illustrate what appears to be the effect of cumulative attacks on our mitochondrial energy production system. This diffuse network has considerable heterogeneity both inside each single cell, and across different cell populations in the body. This complexity means that the first applications of Biplastiq’s technology may be more geared to cases where the damage is not very severe, or the disease etiology (circumstance and cause) is more precisely known. Multifaceted afflictions (like Gulf War Syndrome) may one day be treated with stem cell emissaries loaded with custom mitochondria, but more likely, the first case use will be in energy intensive applications like regeneration or tissue repair.
Today, if I showed up at the ER with a serious medical situation, and were sent home with a shot and a fancy flashlight I might be a bit concerned. However new technologies now in the pipeline are more than just the average bili light. Bili lights, we should mention, are an extremely effective phototherapy tool used to fix the symptoms of jaundice in newborns. In this case blue light converts bilirubin (a breakdown product from hemoglobin normally excreted into the bile) in the body into a form that can be secreted in the normal waste disposal pathways. In this way a simple light protects the child from otherwise inevitable brain damage like cerebral palsy.
Where a bili light is an example of a simple but very useful treatment, what Biplastiq hopes to offer is several steps more advanced. A more apt example of the therapeutic light technology we are talking about now is the DARPA/NASA-funded WARP lamp project. This LED-based device has been successfully applied to wound healing and operates at least in part through the cyctochrome c effect described above. When coupled with genetically modified cells and mitochondria to sharpen, localize, and amplify these kinds of effects, light therapy will have much more to offer. I talked to spokesman Christopher Powell about their new technology and he seemed filled with optimism:
“BiPlastiq is being developed with an eye toward supporting a broad portfolio of regenerative applications. We believe that our strategy has the potential to improve the efficacy of any cell-based therapeutic platform. Generally, we envision that its effect on such platforms would be somewhat analogous to a cutting-edge computer processor’s ability to improve the quality of the latest PC.
As large-scale biotechnology firms make substantial headway into the arena of cellular and gene therapy, we believe there is real opportunity for (smaller) highly specialized firms, like ourselves, to produce the component architecture required to refine these therapies and bring their true potential to light.”
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