Drug for Rare Disorder Linked to Reducing Cholesterol Plaque

Compound being tested in a genetic condition showed promise in treating heart disease in mice

By:  Amy Dockser Marcus (Wall Street Journal)

Updated April 6, 2016 4:19 p.m. ET

Cyclodextrin, a compound now in testing to treat a very rare genetic disease, may have a potential use in treating a much more common condition too: heart disease.

Researchers reported Wednesday in Science Translational Medicine that in mice, cyclodextrin was able to reduce plaque and dissolve cholesterol crystals, which some research suggests could play a role in atherosclerosis, or narrowing of the arteries.

Statins and cholesterol-lowering drugs are highly effective in helping prevent heart attacks and stroke, but don’t adequately treat everyone. The cyclodextrin study may help draw attention to cholesterol crystals as a potential target for treatment. The idea is that cholesterol can crystallize and accumulate in arteries, causing inflammation and triggering or contributing to disease. The research is still in its early days, and positive findings in animals don’t always translate to humans.

“This is a potentially promising therapeutic approach,” said George Abela, chief of cardiology at Michigan State University, who has done extensive research on cholesterol crystals but wasn’t involved in the new study.

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Dr. Abela said he and other researchers are looking for a way to prevent or dissolve cholesterol crystals by testing agents that include aspirin, statins and alcohol, among others. He said they haven’t examined cyclodextrin for this purpose.

“The question is what is the most tolerable and efficient way to extract the crystals,” Dr. Abela said.

Cyclodextrin has long been used to help dissolve and deliver drugs and wasn’t considered an active drug itself. But efforts by scientists, clinicians and patient advocates to find a therapy for a rare genetic condition called Niemann-Pick Type C led to the realization that cyclodextrin might help treat the fatal cholesterol metabolism disorder.

Cyclodextrin is being tested in children with NPC disease in a clinical trial run by Vtesse Inc. A number of other patients with NPC are taking cyclodextrin outside the clinical trial with permission from the Food and Drug Administration.

The idea for the heart-disease study came from a parent of children with NPC disease who are taking cyclodextrin. The parent read a paper about cholesterol crystals and their potential role in heart disease. The parent reached out to one of the authors, Eicke Latz , inquiring whether cyclodextrin might dissolve them.

Dr. Latz, who is the director of the University of Bonn’s Institute of Innate Immunity and principal investigator on the cyclodextrin study, said he believes cyclodextrin makes the cells more efficient in getting rid of cholesterol, lowering the likelihood that cholesterol crystals will form in arteries.

In the mice studied, cyclodextrin worked even when the mice continued to eat a high-cholesterol diet.

Dr. Latz said much more work needs to be done, particularly on dosing if the drug gets to the human-testing stage. In at least some people with NPC disease, cyclodextrin has caused hearing loss.

Write to Amy Dockser Marcus at amy.marcus@wsj.com

In Science, Inspiration Can Come From Unlikely Places

A mom reached out to a scientist with a novel idea for an experiment. Years later, her hunch has blossomed into a published scientific study.

By:  Amy Dockser Marcus (Wall Street Journal)
Updated April 6, 2016 2:08 p.m. ET

In science, ideas can come from anywhere. Still, Eicke Latz was surprised to get an email in 2010 from a stranger proposing an experiment.

Dr. Latz and other researchers had just published a study in Nature proposing that cholesterol crystals that form in the arteries may help trigger  inflammation and heart disease. The scientists wondered in the paper if finding drugs that might dissolve the crystals could make a difference in treating or even preventing the disease.

One of the readers of Dr. Latz’s paper was Chris Hempel of Reno, Nev., the mother of twin girls with a rare and fatal cholesterol-metabolism disorder called Niemann-Pick Type C disease. Her children were receiving cyclodextrin as part of an experimental treatment approved by the U.S. Food and Drug Administration. Ms. Hempel wondered if cyclodextrin might work to dissolve cholesterol crystals. Dr. Latz said the idea was intriguing, and he set out to test it.

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Years later, Ms. Hempel’s inkling has turned into the focus of a newly published scientific study in the journal Science Translational Medicine. Dr. Latz lists Ms. Hempel as one of the co-authors.

“In the end,” he says, “the question turned out to not be so simple to answer.”

Here are edited excerpts of the conversation with Dr. Latz about how those most affected by a particular disease can end up helping to generate science.

WSJ: Have you ever pursued a suggestion from someone who isn’t a scientist?

Dr. Latz: Typically not. If the concept is maybe written up in a very clear way or it is a simple concept you may actually get ideas from people who are not scientists. Those are sometimes the best ideas, because when you have an education on a certain subtopic you are always a little bit biased. You understand what other people have written about the topic, you understand all the knowledge around the topic, or at least you think you understand it, but then sometimes the most obvious things don’t really stay in your mind. They don’t come out because you think too complicated.

WSJ: Can you expand on what some of the advantages an educated patient advocate, but not a trained scientist, might have in coming up with an idea for an experiment?

Dr. Latz: One thing is they probably have a lot of passion for what they read up on and for what they come up with, just because it affects the lives of their loved ones and this is a driving force, to really grasp everything around the disease. They want to get [at] something novel and…want to find something new so they can have a new therapy for their kids or people that have a disease. So I think it’s a special driving force that is in those people.

WSJ: What would be some of the limitations of working on ideas that come from people who don’t have any specialized science training?

Dr. Latz: I don’t think there is a limitation because, in the end, it is something you can test, in a mouse or a test tube or anexperiment. So if the idea is a good idea, it comes out perfectly well and ifit is a bad idea or an idea that is not justified, it will not show the answer.

Addison and Cassidy Hempel, twins with Niemann-Pick Type C disease, take an experimental drug now being tested in heart disease too. Photo: Chris and Hugh Hempel

WSJ: What factors limit more widespread collaboration between scientists and the public?

Dr. Latz: The information we typically get is from peer-reviewed journals. That is something that is not typically open to the general public…it is hidden between certain paywalls because people have to pay for viewing those articles. [But] there are more and more open access policies in science publishing so that other people actually can have access to the scientific literature. That is only one layer. The other layer is the language itself sometimes is a little bit cryptic. It is specialized. You always have to assume the reader has a certain knowledge level about what you write about.

Write to Amy Dockser Marcus at amy.marcus@wsj.com

CNN – Dr. Sanjay Gupta Chronicles Our Fight

Addi & Cassi Featured in an Incredible Wall Street Journal Story

Pulitzer prize winning journalist Amy Marcus spent 6 years following Addi & Cassi, their doctors, and the science community on our journey to find treatments.  In an unprecedented 10 chapter online e-book, the Wall Street Journal has published this remarkable story.

The story (without the amazing videos, audioclips) is featured on the front page of the print version today including an amazing 2 page spread in the center of section A.

What the Wall Street Journal has done with technology is also absolutely fantastic and unprecedented in so many ways.  The story is told with beautiful “images” that are actually moving videos.  This project was an amazing effort by literally dozens of dedicated people as the credits and footnotes clearly indicate.

We are so fortunate to have the support of so many scientists, doctors, families, the NIH, the FDA and our friends at Johnson & Johnson.  As the story so beautifully illustrates, the effort to bring treatments to all NPC patients is indeed an effort of our entire community working together.

We would like to especially thank Amy Marcus for her compassionate and compelling treatment of this complex subject.

Mother of All Lies – Casey Anthony. RIP Caylee. We won’t forget you, Little Sweetheart.

Note: I normally don’t post anything on Addi and Cassi’s website that is not about their disease or something that is medical related. Hugh would say to leave it to Facebook or Tweet about it.

But the case with Casey Anthony and her little daughter Caylee has captured my attention….and my heart.

When you’re in so much pain about losing your own kids to a terrible disease, you can’t imagine a mother suffocating an innocent child and discarding her in a swamp to be eaten by animals.

Peter Gelzinis of the Boston Herald said it all for me!  His commentary is below.

Jury swayed by
mother of all lies

The O.J. Simpson case introduced us to the idea of jury nullification, but it took a 25-year-old bar-hopping party girl, bored by motherhood, to refine the concept.

Yesterday, a Florida jury acquitted Casey Anthony on all three counts of murdering her 2-year-old daughter, Caylee.

Then, this very same jury went on to return four guilty counts of lying to police about . . . that’s right, the murder of her daughter.

Shame on this jury for denying the obvious.

If the O.J. debacle proved anything, it was that the chances of killing your wife and beating the rap are better in California.

Likewise, what we take away from this sad, slimy soap opera in the Sunshine State is that a bimbo looking to detach herself from the burdens of her 2-year-old daughter has a good chance of getting away with murder in Florida.

All you needed to know about the absurdity of yesterday’s verdict was uttered by Casey’s victorious defense lawyer, Jose Baez, who reminded the public that he had never denied his client was a liar.

Quite a victory declaration.

Ah, but then what else could this lawyer say? Even though Casey Anthony was the last person to see her daughter alive, she spent a month denying Caylee’s disappearance to everyone, including her own parents.

Even when the trunk of her car reeked with the stench of death left by a decomposing body, Casey kept lying. She couldn’t even bring herself to conduct a sincere vigil. While the cops searched by day, Casey was hitting the bar scene at night.

But as this trial unfolded, it was clear that such damning “circumstantial evidence” was dwarfed by the suntanned dysfunction of a family who were all more than somewhat wacky.

O.J. was helped tremendously by the behavior of a white LAPD detective branded a racist.

To plug the huge holes in Casey Anthony’s story, she and her lawyers put her father on trial. All of this woman’s malignant deficiencies and narcissism could be explained by the alleged molestation she suffered at the hands of her father, a former homicide detective.

Casey’s lawyers tried to pin Caylee’s death on Dad, suggesting he was the one who put the duct tape over her mouth after she drowned in the family’s pool.

Apparently, that seemed to qualify as reasonable doubt in this jury’s collective consciousness.

And yet they weren’t troubled by a young mother who gets the two-word credo “belle vita,” or beautiful life, tattooed on her body while her dead child is rotting away in the woods.

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