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

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NPC Disease and it’s Connection to Ebola

Amy Marcus at the Wall Street Journal has written a short story about the unexpected connection between NPC and Ebola today.  It is a fascinating article that provides further compelling evidence about 2 concepts.

First, the idea that Rare Disease research can inform the research going on in the “big conditions” like Ebola

Second, it appears that NPC Disease is the unintended outcome of genetic protections that may have evolved in order to protect us against horrible viruses like Ebola.  It appears (from the animal models) that carriers of NPC mutations are more likely to survive an Ebola infection.

We donated our ‘fibroblasts’ (skin cells) in 2009 to a wonderful non-profit bio-bank called The Corriel Institute for Medical Research.  We could not have imagined that our cells would be used by researchers to study Ebola and to discover that the NPC gene and it’s proteins could provide critical answers to how best to treat and protect against Ebola.

The original article on the WSJ pay site is HERE.   A reposted version of the article is HERE on the Global Genes website.

 

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.

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