DiversityNursing Blog

Catharine Paddock PhD

Drug development is a costly and lengthy business, not helped by the fact there is a high failure rate in drug testing due to the reliance on animal models. Animal biology is not an ideal substitute for human biology, but until something better comes along, it is all we have. Now, a new study suggests the organ-on-a-chip method may offer a more ideal model.

Study leader Kevin Healy, a bioengineering professor at the University of California-Berkeley, says:

"It takes about $5 billion on average to develop a drug, and 60% of that figure comes from upfront costs in the research and development phase. Using a well-designed model of a human organ could significantly cut the cost and time of bringing a new drug to market."

As around one third of the candidate drugs that are ditched are those that seem to have a bad effect on the heart, Prof. Healy and colleagues decided to design a model based on the human heart.

They conclude that their work is a major step forward in the development of faster, more accurate ways of testing drug safety. Prof. Healy believes that:

"Ultimately, these chips could replace the use of animals to screen drugs for safety and efficacy."

In their study, they describe how they devised the model and tested it with cardiovascular medications.

'Heart-on-a-chip' contains a network of pulsating cardiac muscle cells

The human heart model that Prof. Healy and colleagues devised is a "heart-on-a-chip" comprising an inch-long silicone device with a thin network of pulsating cardiac muscle cells.

In the journal Scientific Reports, the team says their heart-on-a-chip - which they call a "cardiac microphysiological system (MPS)" - is an ideal tool for testing toxic side effects of new drugs on the human heart because it ticks four important boxes:

1. It uses cells that have human genes
2. The cells are aligned in a way that reflects the structure of human heart tissue
3. It mimics the dynamics of blood flow in heart tissue
4. It can be used for biological, electrophysiological and physiological analysis.

The authors note that using animal models to predict human reactions to drugs often fail because of fundamental differences in biology between species. For example, the ion channels that conduct the electrical pulses that heart cells send out can vary in number and type between animals and humans.

"Many cardiovascular drugs target those channels, so these differences often result in inefficient and costly experiments that do not provide accurate answers about the toxicity of a drug in humans," Prof. Healy explains.

Device is populated with heart cells made from human-induced pluripotent stem cells

The heart-on-a-chip is made of heart cells generated from human-induced pluripotent stem cells - the adult stem cells that can be coaxed to differentiate into various types of tissue.

The heart-on-a-chip has a 3D geometry and spacing that is comparable to that of connective tissue fiber in a human heart. The researchers then populated this with layers of differentiated heart cells, which in the confined geometry were forced to align in one direction.

Microfluidic channels on either side of the cell-populated area perform like blood vessels and mimic the same dynamics of nutrients and drugs diffusing from blood vessels into human tissue.

Such a setup could also serve as a model of how the cells get rid of their waste products, note the authors.

Lead author Dr. Anurag Mathur, a postdoctoral scholar in Healy's lab and a fellow of the California Institute for Regenerative Medicine, explains:

"This system is not a simple cell culture where tissue is being bathed in a static bath of liquid. We designed this system so that it is dynamic; it replicates how tissue in our bodies actually gets exposed to nutrients and drugs."

Heart-on-a-chip tested with four drugs and reacted as expected

The authors explain how within 24 hours of populating the device with heart cells, the engineered heart tissue was beating on its own at the normal rate of 55-80 beats per minute.

The team tested four well-known cardiovascular drugs on the device: isoproterenol, E-4031, verapamil and metoprolol. They used changes in the pulse rate of the tissue to measure the response to the drugs.

The changes in pulse rate were as expected for the drugs. For example, after half an hour of being exposed to isoproterenol - a drug used to treat slow heart rate, or bradycardia - the pulse rate of the heart-on-a-chip increased from 55 to 124 beats per minute.

Multi-organ testing devices could have hundreds of microphysiological cell systems

The engineered tissue remained viable and worked for several weeks. Such a timescale is sufficient for testing several different drugs, Prof. Healy says.

He and his colleagues are now investigating whether the method can be used to model multi-organ interactions. Prof. Healy notes:

"Linking heart and liver tissue would allow us to determine whether a drug that initially works fine in the heart might later be metabolized by the liver in a way that would be toxic."

The team anticipates the "widespread adoption" of organ-on-a-chip for drug screening and disease modeling and foresee devices containing hundreds of microphysiological cell systems. 

The project is funded through the Tissue Chip for Drug Screening Initiative, which is sponsored by the National Institutes of Health.

In October 2014, Medical News Today learned how the University of Kansas is leading the development of a  lab-on-a-chip that promises to detect lung cancer - and possibly other deadly cancers - much earlier. That method, which only uses a small drop of a patient's blood, is also based on microfluid technology. It analyzes the contents of exosomes - tiny bags of molecules that cells release now and again.

Source: www.medicalnewstoday.com

By Linda Carroll

For years Larry Hester lived in darkness, his sight stolen by a disease that destroyed the photoreceptor cells in his retinas. But last week, through the help of a “bionic eye,” Hester got a chance to once again glimpse a bit of the world around him.

Hester is the seventh patient to receive an FDA-approved device that translates video signals into data the optic nerve can process. The images Hester and others “see” will be far from full sight, but experts hope it will be enough to give a little more autonomy to those who had previously been completely blind.

Hester’s doctors at Duke University Eye Center believe that as time goes on the 66-year-old tire salesman from Raleigh, N.C., will be able to “see” more and more. After only five days, there has been remarkable progress.

“I hope that [after some practice] he will be able to do things he can’t do today: maybe walk around a little more independently, see doorways or the straight line of a curb. We don’t expect him to be able to make out figures on TV. But we hope he’ll be more visually connected.” said Dr. Paul Hahn, an assistant professor of ophthalmology at the university in Durham.

It was at Duke three decades ago that Hester learned that something was seriously wrong with his eyes. After a battery of tests, doctors delivered the disheartening news: Hester had retinitis pigmentosa, a disease that would inexorably chip away at the rods and cones in his retinas, eventually leaving him blind.

“It was a pretty devastating blow, frankly,” Hester said. “I was 33 at the time.”

But Larry Hester wasn’t the sort of guy to sit around feeling sorry for himself. With the support of family, friends and a devoted wife, he found a way to live his life as normally as possible, depending on his memory to help him navigate around his home and his workplace.

One day his wife, Jerry, saw a story about a device that might help Larry. The FDA had just approved it for use in people who suffer from the same condition as Larry —some 50,000 to 100,000 in the U.S.  

Larry was just the kind of patient that Hahn was looking for to try out the Argus II Retinal Prosthesis system, and he became the first to get the device at Duke.

Argus was designed to bypass damaged photoreceptors and send signals directly to the next layer of retinal cells, which are on the pathway to the optic nerve.

A miniature video camera seated in a pair of glasses captures what the patient is “looking” at and sends the video through a thin cable to a small external computer that transforms the images into signals that can be understood by that second layer of retinal cells. Those data are then sent back to the glasses, which transmit the information through a small antenna to an array of 60 tiny electrodes that implanted up against the patient’s retina.

The electrodes emit small pulses of electricity that make their way up the undamaged retinal cells to the optic nerves, creating the perception of patterns of light. The hope is that patients will learn to interpret those patterns as images.

Last week with the new glasses perched on his nose, Larry sat in a chair at Duke surrounded by medical staff and his family — all waiting for Hahn to turn on the device. Directly in front of Larry was a brightly lit screen.

“At the count of three, we’re going to hit the start button and we’ll see what happens,” Hahn said.

At three, a smile started to play on Larry’s lips.

“Yes,” he said and the smile broadened across his face. “Oh my goodness!”

Jerry looked at him and exclaimed, “Can you see, Larry?”

After giving her husband a kiss, she asked again, “Can you really see?”

“Yes. Flashing. Big time flashing.”

Experts see the new device as the start of something big.

“It’s a fairly limited device, but it’s an amazing leap forward,” said Dr. Colin McCannel, a retinal expert at the Jules Stein Eye Institute at the University of California, Los Angeles. “It’s not the vision you or I are used to. But for someone who has been in complete darkness it must be amazing to see again. I think it’s absolutely phenomenal.”

Dr. Neil Bressler turns to the space program for an analogy.

“It’s like the first rocket ship that went up and down, or when John Glenn went into orbit,” said Bressler, a professor of ophthalmology and chief of the retina division at Johns Hopkins Medicine. “If you asked can we put a man on the moon the next day the answer would be no. It was the first of many steps to achieve the objective of putting a man on the moon.”

While the device isn’t even close to giving Larry back the vision he was born with, he can see contrasts, which allows him, for example, to distinguish between a white wall and a darkened doorway.

If you’ve lived in darkness for decades, that little bit of new-found vision can be a huge gift.

“The other night I was sitting on a dark leather chair,” Jerry said. “He was able to scan over and see my face because it was lighter. And he reached out and touched my face. That is the first time he had done that in a long time. It was a sweet and precious moment.”

Linda Carroll is a regular contributor to NBCNews.com and TODAY.com. She is co-author of "The Concussion Crisis: Anatomy of a Silent Epidemic” and the recently published “Duel for the Crown: Affirmed, Alydar, and Racing’s Greatest Rivalry.”

Source: www.today.com

By Karen Weintraub

Parkinson's disease is like a "rolling wave" of ever-changing symptoms, not a lightning strike of different events, says its most famous patient, the actor Michael J. Fox.

So when doctors ask for a list of recent symptoms, they miss a lot of the subtleties of the progressive disease.

Hoping to change that, the Michael J. Fox Foundation and Intel announced Wednesday that they are collaborating on a project to track Parkinson's patients 24/7.

Using a device like the popular FitBit (a wristband activity monitor), patients will be tracked over the course of their day, as their medication kicks in and wears off, as food hits their system, as their environment changes and as they sink into sleep. The data generated will be so enormous that Intel's digital expertise will be needed to make sense of it, both organizations said.

The information should lead to new insights into a disease diagnosed in about 60,000 Americans a year, leading to tremors, paralyzing stiffness and physical awkwardness, among other symptoms.

"The answers are within us," Fox said in an interview. "We just need to find a way to let people into our brains both literally and figuratively to help us figure this out."

The collaboration, which started with a small pilot trial of 25 people this spring, aims to measure patient gait, tremors and sleep patterns, among other metrics, and stream the data in real time to the cloud. Intel, which provided the servers and software to collect and manage the data, is also developing algorithms to help analyze it, said Diane Bryant, senior vice president and general manager of Intel's Data Center Group.

Former Intel CEO Andrew Grove has had Parkinson's since 2000, and initiated the discussion between the company and the foundation, Bryant said.

The company isn't disclosing how much it is investing in the project, but Bryant said that costs for this kind of effort have fallen dramatically in recent years. "Ten years ago it would have been ridiculous to consider" a project like this, she said.

The collaboration is Intel's first step into health care, but it likely won't be the last.

"It's a wonderful first step for us," Bryant said. Health care lends itself well to so-called big-data analytics, because there is so much information to collect on a patient, from symptoms to genetics to lab results.

Fox Foundation CEO Todd Sherer said doctors score the disease's severity based on how the patient feels during a visit – but symptoms can change minute by minute, from near normal to completely disabling.

"If the doctor is running 15 minutes late, the assessment could be completely different than if they'd seen the disease 15 minutes earlier," Sherer said.

Also, he said, sometimes patients minimize symptoms for their doctor, or time their medication so they'll perform well during the visit. "The doctor might say everything's doing great, and we'll hear from the spouse: 'You should have seen them yesterday.' "

The same problems also make research into the disease more difficult. It's hard for researchers to get a realistic view of whether a treatment is effective, if they only get occasional snapshots of a patient.

The new devices will therefore provide a much more realistic – and objective – view of the disease than has been possible before, Sherer said.

If shown effective during pilot studies, he said, the devices will likely be used both for clinical research trials – in which the patient data will be anonymous – and, say, for a week before a doctor's visit, to provide an update on a patient's disease.

Source: www.usatoday.com