Update September 30, 2017
Lab-made “mini organs” helping doctors treat cystic fibrosis
This illustration provided by the Hubrecht Institute
in Utrecht, Netherlands shows organoids (mini organs), created from the
intestinal tissues of a patient. (Hubrecht Institute via AP)
Netherlands (AP) - Els van der Heijden, who
has cystic fibrosis, was finding it ever harder to breathe as her lungs
filled with thick, sticky mucus. Despite taking more than a dozen pills
and inhalers a day, the 53-year-old had to stop working and scale back
doing the thing she loved best, horseback riding.
Doctors saw no
sense in trying an expensive new drug because it hasn’t been proven to
work in people with the rare type of cystic fibrosis that van der
scraped a few cells from van der Heijden and used them to grow a mini
version of her large intestine in a petri dish. When van der Heijden’s
“mini gut” responded to treatment, doctors knew it would help her too.
“I really felt,
physically, like a different person,” van der Heijden said after taking
a drug - and getting back in the saddle.
This experiment to
help people with rare forms of cystic fibrosis in the Netherlands aims
to grow mini intestines for every Dutch patient with the disease to
figure out, in part, what treatment might work for them. It’s an early
application of a technique now being worked on in labs all over the
world, as researchers learn to grow organs outside of the body for
treatment - and maybe someday for transplants.
So far, doctors
have grown mini guts - just the size of a pencil point - for 450 of the
Netherlands’ roughly 1,500 cystic fibrosis patients.
“The mini guts are
small, but they are complete,” said Dr. Hans Clevers of the Hubrecht
Institute, who pioneered the technique. Except for muscles and blood
vessels, the tiny organs “have everything you would expect to see in a
real gut, only on a really small scale.”
organoids mimic features of full-size organs, but don’t function the
same way. Although many of the tiny replicas are closer to undeveloped
organs found in an embryo than adult ones, they are helping scientists
unravel how organs mature and providing clues on how certain diseases
might be treated.
In Australia, mini
kidneys are being grown that could be used to test drugs. Researchers in
the U.S. are experimenting with tiny bits of livers that might be used
to boost failing organs. At Cambridge University in England, scientists
have created hundreds of mini brains to study how neurons form and
better understand disorders like autism. During the height of the Zika
epidemic last year, mini brains were used to show the virus causes
malformed brains in babies.
In the Netherlands,
the mini guts are used as a stand-in for cystic fibrosis patients to see
if those with rare mutations might benefit from a number of pricey
drugs, including Orkambi. Made by Vertex Pharmaceuticals, Orkambi costs
about 100,000 euros per patient every year in some parts of Europe, and
it’s more than double that in the U.S., which approved the drug in 2015.
Despite being initially rejected by the Dutch government for being too
expensive, negotiations with Vertex were reopened in July.
Making a single
mini gut and testing whether the patient would benefit from certain
drugs costs a couple of thousand euros. The program is paid for by
groups including health insurance companies, patient foundations and the
government. The idea is to find a possible treatment for patients, and
avoid putting them on expensive drugs that wouldn’t work for them.
About 50 to 60
patients across the Netherlands have been treated after drugs were
tested on organoids using their cells, said Dr. Kors van der Ent, a
cystic fibrosis specialist at the Wilhelmina Children’s Hospital, who
leads the research.
Clevers made a
discovery about a decade ago that got researchers on their way. They
found pockets of stem cells, which can turn into many types of other
cells, in the gut. They then homed in a growing environment in the lab
that spurred these cells to reproduce rapidly and develop.
“To our surprise,
the stem cells started building a mini version of the gut,” Clevers
Cystic fibrosis is
caused by mutations in a single gene that produces a protein called
CFTR, responsible for balancing the salt content of cells lining the
lungs and other organs.
To see if certain
drugs might help cystic fibrosis patients, the medicines are given to
their custom-made organoids in the lab. If the mini organs puff up, it’s
a sign the cells are now correctly balancing salt and water. That means
the drugs are working, and could help the patient from whom the mini gut
also using the mini guts to try another approach they hope will someday
work in people - using a gene editing technique to repair the faulty
cystic fibrosis gene in the organoid cells.
are underway in the Netherlands and the U.S. to test whether organoids
might help pinpoint treatments for cancers involving lungs, ovaries and
While the idea
sounds promising, some scientists said there are obstacles to using mini
organs to study cancer.
Growing a mini
cancer tumor, for example, would be far more challenging because
scientists have found it difficult to make tumors in the lab that behave
like in real life, said Mathew Garnett of the Wellcome Trust Sanger
Institute, who has studied cancer in mini organs but is not connected to
Also, growing the
cells and testing them must happen faster for cancer patients who might
not have much time to live, he said.
wants to one day make organs that are not so mini.
“My dream would be
to be able to custom-make organs,” he said, imagining a future where
doctors might have a “freezer full of livers” to choose from when sick
Others said while
such a vision is theoretically possible, huge hurdles remain.
“There are still
enormous challenges in tissue engineering with regards to the size of
the structure we’re able to grow,” said Jim Wells, a pediatrics
professor at the Cincinnati Children’s Hospital Medical Center. He said
the mini organs are far smaller than what would be needed to transplant
into people and it’s unclear if scientists can make a working,
life-sized organ in the lab.
There are other
limitations to growing miniature organs in a dish, said Madeline
Lancaster at Cambridge University.
“We can study
physical changes and try to generate drugs that could prevent
detrimental effects of disease, but we can’t look at the complex
interplay between organs and the body,” she said.
For patients like
van der Heijden, who was diagnosed with cystic fibrosis as a toddler,
the research has helped her regain her strength. Vertex agreed to supply
her with the drug.
“It was like
somebody opened the curtains and said, ‘Sunshine, here I am, please come
out and play’,” she said. “It’s strange to think this is all linked to
some of my cells in a lab.”
Update September 23, 2017
New drug reduces heart attacks, but is that enough?
A new type of cholesterol drug meant to
prevent heart attacks and other complications clearly did so, in an
unusually large study whose results were announced Tuesday, Aug. 29,
2017, at a conference of heart specialists. (AP Photo/Mel Evans, File)
Linda A. Johnson
Trenton, N.J. (AP) - So-so
results for a new type of cholesterol drug have left Merck in a
quandary: Does the company try to bring it to market or scrap it?
A large, long-term study of the
drug showed that it prevents heart attacks and reduces the need for
heart procedures, while three similar drugs developed by rivals failed.
But the drug, anacetrapib, only reduced those complications by 9
Now Merck, which has spent 13 years
and likely hundreds of millions of dollars testing the drug, has to
decide whether to spend even more to seek approval from regulators and
convince people to buy it in a market full of cholesterol drugs.
The results of the 30,450-patient
study were announced Tuesday, Aug. 29, 2017, at a conference of heart
specialists in Barcelona, Spain and published in the New England
Journal of Medicine. The study found that anacetrapib is
safe and somewhat effective.
That kind of result is normally
enough to seek approval to market a new medicine, especially for heart
disease, which is the top killer in many developed countries. Yet even
after seeing the results weeks ago, Merck says its executives are still
consulting with medical experts and regulators on whether to go through
the costly process of applying for approval.
Analyst Steve Brozak, president of
WBB Securities, predicts Merck will do so, given anacetrapib’s safety,
the huge pool of potential patients and all the resources Merck has
poured into the drug.
“This will get used,” Brozak said.
Merck would likely price the bill
somewhere between the two extremes that now define the market for
Generic versions of brand-name
statin cholesterol pills including Lipitor, Crestor and Merck’s own
Zocor now cost $10 to $20 a month. Repatha and Praluent, two new
injected medicines in a different drug category that have been shown to
dramatically reduce cholesterol, cost $14,000 a year.
Georgetown University cardiologist
Dr. Allen J. Taylor said he thinks the drug would be approved by the
Food and Drug Administration despite its “relatively weak benefit.”
“If you were discussing this with
patients,” Taylor said, “you would have to tell them that when you start
this, you’ll have to take it for four years to have a 1 percent chance
of preventing an event,” meaning a heart attack or a procedure such as
bypass surgery or implanting a stent to keep an artery open.
Taylor said it’s still unclear how
anacetrapib controls cholesterol, which would make it hard for doctors
to determine which patients would benefit much from it. But he and
Brozak praised the company for doing such an exhaustive, expensive study
in an era when many studies are quick and relatively small, sometimes
producing unclear results.
In the study, patients getting
anacetrapib plus a statin for four years had, on average, lower levels
of bad cholesterol and other fats, and higher levels of good
cholesterol, compared to a group getting a statin and a dummy pill. But
Merck’s drug didn’t prevent any deaths from heart attacks or other
Anacetrapib’s only worrisome side
effect was a long-term accumulation of the drug in patients’ fatty
tissue. It’s unknown if that will cause problems, so Merck plans to
study that by following some participants for two years after they stop
taking the drug.
Update September 16, 2017
US clears breakthrough gene therapy for childhood leukemia
In this July
9, 2015, photo, provided by Novartis Pharmaceuticals Corp.,
human T cells belonging to cancer patients arrive at Novartis
Pharmaceuticals Corp.’s Morris Plains, N.J., facility. (Brent
Stirton/Novartis Pharmaceuticals Corp. via AP)
Washington (AP) - Opening a new era
in cancer care, U.S. health officials have approved a
breakthrough treatment that genetically engineers patients’ own
blood cells into an army of assassins to seek and destroy
and Drug Administration said the approval was historic, the
first gene therapy to hit the U.S. market. Made from scratch for
every patient, it’s one of a wave of “living drugs” under
development to fight additional blood cancers and other tumors,
Pharmaceuticals set the price for its one-time infusion of
so-called “CAR-T cells” at $475,000, but said there would be no
charge for patients who didn’t show a response within a month.
“This is a
brand new way of treating cancer,” said Dr. Stephan Grupp of
Children’s Hospital of Philadelphia, who treated the first child
with CAR-T cell therapy - a girl who’d been near death but now
is cancer-free for five years and counting. “That’s enormously
treatment uses gene therapy techniques not to fix
disease-causing genes but to turbocharge T cells, immune system
soldiers that cancer too often can evade. Researchers filter
those cells from a patient’s blood, reprogram them to harbor a
“chimeric antigen receptor” or CAR that zeroes in on cancer, and
grow hundreds of millions of copies. Returned to the patient,
the revved-up cells can continue multiplying to fight disease
for months or years.
completely different way to harness the immune system than
popular immunotherapy drugs called “checkpoint inhibitors” that
treat a variety of cancers by helping the body’s natural T cells
better spot tumors. CAR-T cell therapy gives patients stronger T
cells to do that job.
entering a new frontier in medical innovation with the ability
to reprogram a patient’s own cells to attack a deadly cancer,”
said FDA Commissioner Scott Gottlieb.
CAR-T version, developed by Novartis and the University of
Pennsylvania, is approved for use by several hundred patients a
year who are desperately ill with acute lymphoblastic leukemia,
or ALL. It strikes more than 3,000 children and young adults in
the U.S. each year and while most survive, about 15 percent
relapse despite today’s best treatments.
In a key
study of 63 advanced patients, 83 percent went into remission
soon after receiving the CAR-T cells. Importantly, it’s not
clear how long that benefit lasts: Some patients did relapse
months later. The others still are being tracked to see how they
far higher percentage of patients go into remission with this
therapy than anything else we’ve seen to date with relapsed
leukemia,” said Dr. Ted Laetsch of the University of Texas
Southwestern Medical Center, one of the study sites. “I wouldn’t
say we know for sure how many will be cured yet by this therapy.
There certainly is a hope” that some will be.
patients suffered side effects that can be grueling, even
life-threatening. An immune overreaction called “cytokine
release syndrome” can trigger high fevers, plummeting blood
pressure and in severe cases organ damage, side effects that
require sophisticated care to help patients without blocking the
cancer attack. The FDA designated a treatment for those side
remarkable technology,” said Dr. Mikkael Sekeres of the American
Society of Hematology. But, he cautioned that CAR-T “isn’t a
concerns, sometimes leukemia can develop resistance, and
sometimes patients worsen while waiting for their new cells,
said Sekeres, who directs the Cleveland Clinic’s leukemia
program and wasn’t involved with CAR-T testing.
“Unfortunately leukemia grows so rapidly that it can evade even
the smartest of our technologies,” he added.
ensure patient safety, the FDA is requiring Novartis to offer
CAR-T therapy only through medical centers specially trained and
certified to handle the complicated treatment. Novartis expects
to have 32 centers around the country, mostly in large cities,
running by year’s end, with the first 20 offering care within
the next month.
collected immune cells will be frozen and shipped to a Novartis
factory in New Jersey that creates each dose, a process the
company says should take about three weeks. The $475,000 price
tag doesn’t include the cost of needed hospitalizations, travel
to a certified hospital and other expenses.
conference call Wednesday, Novartis executives said the company
is working with the Medicaid program and private insurers and
expects broad coverage, and will offer some financial assistance
with such things as copay and travel costs. But they didn’t
promise all patients would be able to get the therapy.
patients, the new CAR-T therapy might replace bone marrow
transplants that cost more than half a million dollars, noted
Grupp, who led the Novartis study.
want to be an apologist for high drug prices in the U.S.,” Grupp
stressed. But if it’s the last treatment they need, “that’s a
really significant one-time investment in their wellness,
especially in kids who have a whole lifetime ahead of them.”
“This is a
turning point in the fight” against ALL, said Penn’s Dr. Carl
June, who pioneered the therapy.
But he and
other researchers say thousands more patients eventually may
benefit. Kite Pharma’s similar CAR-T brand, developed by the
National Cancer Institute, is expected to win approval later
this year to treat aggressive lymphoma, and Juno Therapeutics
and other companies are studying their own versions against
blood cancers including multiple myeloma.
around the country also are trying to make CAR-T therapies that
could fight more common solid tumors such as brain, breast or
pancreatic cancers - a harder next step.
narrow in scope, today’s FDA ruling is a milestone,” said Dr.
David Maloney of the Fred Hutchinson Cancer Research Center in
Seattle, whose team has worked with Juno and is researching
CAR-T in a variety of cancers. “Approvals are an important step,
but they’re just the beginning.”
Is it really Lyme? Researchers
developing a new test to tell
undated photo provided by the U.S. Centers for Disease Control and
Prevention (CDC), a blacklegged tick - also known as a deer tick.
Diagnosing if a tick bite caused Lyme or something else can be difficult
but scientists are developing a new way to catch the disease early,
using a “signature” of molecules in patients’ blood. (CDC via AP)
- Diagnosing if a tick bite caused Lyme or
another disease can be difficult but scientists are developing a new way
to do it early - using a “signature” of molecules in patients’ blood.
It’s still highly
experimental, but initial studies suggest the novel tool just might
uncover early-stage Lyme disease more accurately than today’s standard
test, researchers reported Wednesday. And it could tell the difference
between two tick-borne diseases with nearly identical early symptoms.
“Think about it as
looking at a fingerprint,” said microbiology professor John Belisle of
Colorado State University, who helped lead the research.
Lyme disease is
estimated to infect 300,000 people in the U.S. every year. Lyme-causing
bacteria are spread by blacklegged ticks - also called deer ticks -
primarily in the Northeast and Midwest, although their range is
spreading. Lyme typically starts as a fever, fatigue and flu-like
symptoms - often but not always with a hallmark bulls-eye rash - and
people usually recover quickly with prompt antibiotics. But untreated,
Lyme causes more serious complications, including swollen joints and
arthritis, memory and concentration problems, even irregular heartbeat.
Yet today’s best
available test often misses early Lyme. It’s considered no more than 40
percent accurate in the first few weeks of infection. It measures
infection-fighting antibodies the immune system produces. Those take a
while to form, making the test more useful a month or more after
infection sets in than when people first start feeling ill.
“We are trying our
best to come up with something to help the diagnosis in the very early
stages of this infection,” said microbiologist Claudia Molins of the
Centers for Disease Control and Prevention, who teamed with Belisle to
develop a new test. “Our goal really is to try to fill that gap.”
The new approach
essentially looks for a biochemical fingerprint that shows the body is
beginning to respond to an infection, long before antibodies mobilize.
It’s based on cellular metabolism, subtle changes in the kind and amount
of small molecules that cells produce, such as sugars and amino acids
First, Belisle and
Molins found a signature - specific changes in those metabolites - that
enabled them to distinguish between blood from Lyme patients and from
The tougher hurdle:
Could the tool also tell the difference between Lyme and a disease with
very similar symptoms? To tell, they compared a mysterious Lyme
look-alike called Southern Tick-Associated Rash Illness, or STARI.
STARI is spread by
a different tick, the Lone Star tick that is found widely throughout the
East and Southeast, areas that overlap with the Lyme-carrying
blacklegged ticks. STARI involves a round rash and other symptoms
similar to early Lyme, and is treated with the same antibiotic - but
it’s not caused by the same bacteria. In fact, scientists don’t yet know
the cause of STARI, and there’s no test for it. The only way to identify
STARI is to definitively rule out other ailments.
stored blood samples from people determined to have either Lyme or
STARI, Belisle and Molins found biomarkers that could tell the two
disease apart. Using those markers to study additional blood samples,
they concluded their tool was 82 percent accurate in determining early
Lyme - far better than today’s standard, Molins said.
The research was
published in the journal Science Translational Medicine.
“It is a very novel
way of looking at diagnosis,” said Dr. John Aucott, who directs Johns
Hopkins University’s Lyme Disease Clinical Research Center. He was not
involved in the new study, and notes that other test approaches are
being explored, too.
Creating a test
will take several more years of research, cautioned Molins. First, the
team is turning its sophisticated metabolic-measuring techniques into a
test that standard laboratories could use. Then, with next spring’s tick
season, researchers will start a new round of testing.
cautions that other infections unrelated to ticks can be confused with
Lyme, too, so any new test also would have to rule out those
But better early
diagnosis isn’t the only need, he stressed. Today’s Lyme test also can’t
prove if antibiotic treatment was successful, because it can detect
antibodies even years after people recovered. He wonders if tracking
cellular metabolism could solve that problem.
“If you can show
the host metabolic signature goes back to normal, that could be a great
test of cure,” he said.
Science Says: DNA test results may not change health habits
Institutes of Health (NIH) Director Francis Collins poses for a portrait at
the NIH headquarters in Bethesda, Md., Friday, July 28, 2017. After DNA
testing showed he was predisposed to Type 2 diabetes, which is more likely
to develop if a person is overweight or obese, Collins shed 35 pounds (16
kilograms). (AP Photo/Sait Serkan Gurbuz)
New York (AP) -
If you learned your DNA made you more susceptible to getting a disease,
wouldn’t you work to stay healthy?
You’d quit smoking, eat
better, ramp up your exercise, or do whatever else it took to improve your
odds of avoiding maladies like obesity, diabetes, heart disease or cancer,
The scientific evidence
says: Don’t bet on it.
DNA testing for disease
risk has recently expanded in the U.S. The company 23andMe recently started
selling the nation’s first approved direct-to-consumer DNA tests that
evaluate the buyer’s genetic risk for certain disease or conditions. That
go-ahead came in April, about three years after it was told to stop selling
such kits until it got the OK from regulators.
The field also gained a
new entrant in July, when a company called Helix launched an online
marketplace for DNA tests, including some for genetic health risk. Helix
decodes a consumer’s DNA and passes the results along to another company for
analysis. A request for the currently available health tests must be
approved by a physician’s group that reviews the customer’s medical history.
DNA tests for diseases
typically assess genetic predisposition to getting sick. They don’t provide
absolute predictions about whether or not a disease will strike. Genetic
risk is only part of a person’s overall risk, which includes influence from
other things like a person’s lifestyle.
While some disease are
caused by a single malfunctioning gene, more common illnesses are influenced
by multiple genes, and often each gene nudges a person’s risk only slightly.
A 23andMe test that
includes ancestry and other information goes for $199. Helix’s decoding
costs $80, while the currently available health-risk analyses cost $150 and
$125. Both companies use a saliva sample for the test.
Last year, researchers
published an analysis that combined 18 studies of people who got
doctor-ordered DNA test results about disease risks. None involved
direct-to-consumer tests; participants were drawn mostly from medical
clinics or elsewhere. Eight of the 18 studies were done in the United
The result? Getting the
DNA information produced no significant effect on diet, physical activity,
drinking alcohol, quitting smoking, sun protection or attendance at
That fits with other
results showing that, on balance, getting the information “has little if any
impact on changing routine or habitual behaviors,” said psychologist Theresa
Marteau of Britain’s Cambridge University, a study author.
In an interview, Dr.
James Lu, a co-founder of Helix, agreed that the evidence on whether people
change their lifestyles in response to DNA information is mixed. But he said
it’s more likely if they get the right information, education and support.
“We’re learning a lot
as the field evolves,” Lu said.
Marteau is not claiming
that testing never changes behavior. She notes the example of Dr. Francis
Collins, director of the U.S. National Institutes of Health. After DNA
testing showed he was predisposed to Type 2 diabetes, which is more likely
to develop if a person is overweight or obese, Collins shed 35 pounds (16
“It was a kick in the
pants,” Collins explained. “It was an opportunity to wake up and say, maybe
I’m not going to be immortal and maybe there are things I am doing to myself
that aren’t healthy that I ought to change.”
Dr. Robert C. Green of
Brigham and Women’s Hospital in Boston, whose research indicates DNA test
results can change health behavior, said cases like Collins are just the
It’s very hard to get
people to improve health habits, and even when they do, it’s hard for
researchers to prove that DNA test results were responsible, he said. So
it’s no surprise that evidence favoring an effect is limited, he said.
“It doesn’t necessarily
mean that it doesn’t help some people,” said Green, who’s also a scientific
adviser to several companies involved in genetic testing.
He and co-authors in
May reported evidence that simply going through the process of DNA testing
may slightly improve diet and exercise, regardless of what the results
reveal. Maybe the experience serves to remind and motivate people about
beneficial health behaviors, the authors said.
Green also said that
people seek such results for a number of reasons, including simple
curiosity, so the value of DNA testing should not be judged simply by
whether it changes health behavior.
“I think people have a
right to this information,” he said.