Prof. Colleen Aldous: Spider-Man’s power off switch is real; it’s already lowering cholesterol in SA

What does a Marvel blockbuster have to do with your cholesterol? More than you’d think. In Spider-Man: Brand New Day, RNA interference switches off Peter Parker’s unwanted powers. Fiction, surely? Not entirely. The technique is real, and South Africa has already registered it. Inclisiran, sold here as Sybrava, lowers “bad” LDL cholesterol with an injection every six months once treatment is underway. This explainer from UKZN’s Prof Colleen Aldous covers how “gene silencing” works, how it’s helping patients with rare inherited diseases, and where its limits lie. Spoiler: a spider bite still won’t have you climbing walls. The science is impressive enough..By Prof. Colleen Aldous.A spider bite changes Peter Parker’s life. He gains superhuman strength, climbs walls and develops senses that warn him of danger. This is the Spider-Man story. His attempts to control those powers offer an opportunity to explain some real science.In the movie, Spider-Man: Brand New Day, RNA interference is used to suppress Spider-Man's unwanted powers. The name sounds suited to a superhero film, but medicines using this approach already exist. One is registered in South Africa for lowering cholesterol.To understand how it works, we need to start with the instructions inside our cells.Genes are sections of DNA. Many carry instructions for making proteins. We tend to associate protein with food and muscle, but proteins made in our cells do much of the work that keeps us alive. They help muscles contract, carry substances through the blood, pass signals between cells and control chemical reactions.Think of DNA as an instruction book that the cell keeps safe in its nucleus. When a particular protein is needed, the cell makes a working copy of the relevant instructions. That copy is called messenger RNA (mRNA). The mRNA leaves the nucleus and the cell reads it and builds the protein.The amount produced is important, as is the place and timing. Most cells contain essentially the same DNA, yet a skin cell behaves differently from a nerve cell because it uses different combinations of those instructions.This is where the spider bite explanation becomes science fiction. Venom cannot deliver everything needed to rebuild a person with a spider’s abilities. Even if scientists deliberately put a spider gene into human cells, the cells might produce a particular spider protein. That would be a long way from creating Spider-Man.Making silk, for example, requires more than the instructions for a silk protein. The animal also needs structures that produce, store and spin it. A human cell making that protein would not suddenly give its owner a web-shooting wrist.The film’s idea of reducing protein production has a scientific basis.Scientists can design a small piece of RNA to match a particular mRNA, which helps the cell find and destroy that message. With fewer copies of the instructions available, the cell makes less of the protein. This is RNA interference, often shortened to RNAi. The medicines use molecules called small interfering RNAs, or siRNAs.The original DNA instructions remain in place. We are reducing how much they are used. The term “gene silencing” describes this, although the reduction may be incomplete.This can help when a protein contributes to disease. The siRNA Patisiran, for example, reduces production of a protein called transthyretin. In an inherited disease, this protein can fold incorrectly and accumulate in tissues, damaging nerves and other organs. Reducing its production helps treat the associated nerve disease.Another use concerns a rare inherited cause of kidney stones. In primary hyperoxaluria type 1, the liver produces excessive amounts of oxalate. This substance can combine with calcium to form crystals and stones, and can cause serious kidney damage. Lumasiran, sold as Oxlumo, reduces the production of a liver enzyme called glycolate oxidase. Enzymes are proteins that help chemical reactions take place. Reducing this enzyme slows a step that supplies material for oxalate production, lowering the amount of oxalate in the blood and urine. The medicine is given by injection under the skin. It addresses the excess oxalate that contributes to stone formation in this particular inherited condition. It does not dissolve existing stones and is not a general treatment for everyone who develops kidney stones. It is approved overseas, but not yet available in South Africa.A more familiar problem for South African readers is high cholesterol. Inclisiran, sold here as Sybrava, reduces production of a liver protein called PCSK9. This allows the liver to retain more of the receptors that collect LDL cholesterol from the blood. LDL is often called “bad cholesterol”.South Africa’s medicines regulator, SAHPRA, authorised it in September 2022. The registered use is alongside diet and the highest tolerated statin treatment in adults with specified high-cholesterol conditions. A healthcare professional gives an injection under the skin, followed by another at three months and then one every six months.That long interval is useful for patients. It also shows why Spider-Man could not expect his powers to return immediately after removing an inhibitor. Some RNAi treatments continue working inside cells for months.Another treatment shows how carefully scientists must understand the system they are changing. In haemophilia, blood does not clot adequately. Fitusiran, approved in the United States, reduces a protein that normally slows clotting. Reducing this brake helps prevent bleeding. Patients need monitoring because too much clotting can also cause harm. .Read more:.The Economist: Can you eat your way to lower cholesterol?.These examples show both the possibilities and the limits. A treatment must reach the correct cells and reduce the intended protein sufficiently to help. The same protein may have multiple functions, so reducing it can have unintended consequences.Nor will stopping new protein production immediately remove protein already present. Changes that have developed in an organ or tissue may persist. Timing, dose and delivery all matter.Spider-Man gives us a way into this science, provided we keep those distinctions clear. We can already influence the use of particular genetic instructions to treat disease. Each application depends on understanding what the protein does, where it is produced and what happens when there is less of it. That is a substantial medical achievement in its own right..Sign up for your early morning brew of the BizNews Insider to keep you up to speed with the content that matters. The newsletter will land in your inbox every morning on weekdays. Register here.Support South Africa's bastion of independent journalism, offering balanced insights on investments, business, and the political economy, by joining BizNews Premium. Register here.If you prefer WhatsApp for updates, sign up to the BizNews channel here.

Prof. Colleen Aldous: Spider-Man’s power off switch is real; it’s already lowering cholesterol in SA

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