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
atherosclerosisthe 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 metabolismeven 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 cyclodextrina drug already approved for use in humans by the US Food
and Drug Administrationmay 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 cholesterollowering drugs, which are not always effective, particularly when patients
dont 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 cyclodextrins 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 doesnt 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 cyclodextrins therapeutic potential came in a 2004

scientific publication. Researchers were searching for a treatment for an ultrarare 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 Alzheimers 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 neurosteroidgiven

with the carrier cyclodextrinseemed 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 allit 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 couldnt 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 twinsand they won. Regular treatments gradually
improvedalthough didnt curethe 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 theres too
much cholesterol in the blood stream, can trigger inflammation. The immune
response then produces a snowball effect eventually leading to the
development of plaqueslayers 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
concludeall thanks to some motivated parents.