Two parents’ quest to save their twin daughters’ lives from a rare, degenerative genetic disorder may end up saving and improving the lives of millions.

After digging through medical literature and fitting pieces of data together, the non-medically trained couple contacted German researchers and suggested that a chemical called cyclodextrin may be able to treat atherosclerosis—the hardening of arteries with cholesterol-rich plaques, which is a precursor to heart attack, stroke, and other cardiovascular diseases.

The researchers, Eicke Latz at the University of Bonn and colleagues, followed up on the parents’ hypothesis and found that in mice, cyclodextrin indeed blocked plaque formation, melted away plaques that had already formed in arteries, reduced atherosclerosis-associated inflammation, and revved up cholesterol metabolism—even in rodents fed cholesterol-rich diets. In petri dish-based tests, the researchers found that the drug seemed to have the same effects on human cells and plaques.

The findings, published Wednesday in Science Translational Medicine, suggest that cyclodextrin—a drug already approved for use in humans by the US Food and Drug Administration—may be highly effective at treating and preventing heart disease.

Currently, cardiovascular diseases are the leading cause of death worldwide, and around 43 percent of Americans have high cholesterol, which can lead to atherosclerosis. Typical treatments include statins and other cholesterol-lowering drugs, which are not always effective, particularly when patients don’t adhere to doctor-prescribed, low-cholesterol diets.

While Latz and co-authors stress that clinical trials are needed to validate the effects of cyclodextrin, the researchers note that it would be fairly easy to repurpose the drug to treat and prevent cardiovascular diseases.

But, while cyclodextrin’s road ahead may be clear, its path to medical treatments was oddly bumpy.

Sweet solution?

The chemical, which is simply a bunch of sugar molecules assembled in a ring, is already widely used in medications and foods. Because the outside of the ring is hydrophilic (it mixes with water) and the inside of the ring is hydrophobic (it doesn’t mix with water), cyclodextrin can trap chemicals inside the ring and help them mix into medicines and foods. In medications, cyclodextrin acts as a ‘carrier’ that make active drugs dissolve better in the body. Cyclodextrin is also used in foods, such as mayonnaise, sweets, and butter, to stabilize flavors and emulsifications and to remove cholesterol. But besides its role as an additive, it was largely overlooked by researchers.

One of the first inklings of cyclodextrin’s therapeutic potential came in a 2004 scientific publication. Researchers were searching for a treatment for an ultra-rare genetic disorder called Niemann-Pick type C disease (NPC), which likely affects only a few hundred patients in the US. The disease is caused by a genetic mutation that breaks a protein responsible for shuttling cholesterol in cells. Because cholesterol is a vital building block to cell membranes and various organic molecules, its transport through the body and its cells is critical for proper health. In the absence of a working transporter, cholesterol gradually piles up in cells throughout the body, causing organ dysfunction, neurodegeneration, and eventual death.

NPC is sometimes called childhood Alzheimer’s because kids with the disease are often diagnosed after they develop symptoms similar to dementia, including deteriorating memory, balance, and verbal skills.

In the 2004 study, researchers presented data that a neurosteroid—given with the carrier cyclodextrin—seemed to help mice that were genetically engineered to have a broken cholesterol transporter. A single dose, the researchers found, doubled the life expectancy of the mice.

While other researchers rushed to repeat the experiment, which validated the finding, it took several years for researchers to figure out what was really going on: that the neurosteroid had no effect on the mice at all—it was the cyclodextrin.

Enter the Hempels

As researchers rolled out data on cyclodextrin, a couple named Chris and Hugh Hempel in Reno, Nevada, paid close attention. In 2007, their twin daughters, Addi and Cassi, then three years old, were diagnosed with NPC. As doctors repeatedly told them there was nothing to be done, the parents kept digging into the research and looking for a cure.

They found cyclodextrin and initially tried using it in oral doses, which is known to be safe. However, the chemical couldn’t effectively reach the brain that way. The couple made headlines with their tireless efforts to get drug companies, the FDA, and doctors to let them try out intravenous treatments of cyclodextrin for their twins—and they won. Regular treatments gradually improved—although didn’t cure—the twins’ conditions. Cyclodextrin is now in clinical trials to treat other kids with NPC.

Meanwhile, in 2010, Latz and colleagues published a study in Nature showing that cholesterol crystals, which accumulate along arteries when there’s too much cholesterol in the blood stream, can trigger inflammation. The immune response then produces a snowball effect eventually leading to the development of plaques—layers of cholesterol crystals, immune cells, and calcified lesions in the artery wall. Upon reading the study, Chris Hempel contacted Latz and told him about their experience with cyclodextrin clearing cholesterol from cells. Perhaps the sweet chemical could also clear it from plaques.

In mice fed high-cholesterol diets, cyclodextrin cleared away plaques and helped prevent more plaques from forming, Latz and his colleagues found. The chemical also activated cholesterol metabolism that boosted clearance of the waxy substance from arteries, plus dampened inflammation responses that spur atherosclerosis.

Using blood vessel tissue from human patients with atherosclerosis, researchers found that cyclodextrin induced the same changes in the human cells as it did in the mice.

The study, which includes Hempel as a coauthor, shows that cyclodextrin is a promising new treatment for atherosclerosis in humans, the researchers conclude—all thanks to some motivated parents.

Science Translational Medicine, 2015. DOI: 10.1126/scitranslmed.aad6100 (About DOIs).