, patients have also prescribed oral medication that would help the ureter relax. However, many studies have
offered conflicting evidence on the effectiveness of this drug.
team from MIT and Massachusetts General Hospital has proposed a new line of treatment
and the study is featured in
The senior author of the study, Michael Cima is a
member of MIT's Koch Institute for Integrative Cancer Research and also the
David H. Koch Professor of Engineering in the Department of Materials Science
and Engineering at MIT. The lead author is Christopher Lee, a PhD recipient
from the Harvard-MIT Division of Health Sciences and Technology.
They have identified a drug combination that
would help walls of the ureter relax. Using an instrument similar to a
catheter, the drug could be delivered directly to the ureter.
says that the stones could move easily through the ureter, which is a tube that
connects the kidneys to the bladder, if the walls are relaxed.
"We think this could significantly impact kidney
stone disease, which affects millions of people,"
Following the passing of stones, sometimes stents are required to be inserted
into the ureter in order to prevent blockage and collapse of the tube. This new
treatment would also make the insertion easier and less painful.
Background of the Study
the co-director of the Kidney Stone Program at MGH and also a study author,
alongside Cima, was contemplating ways to improve the treatment of kidney
. They devised this approach, which would be a better
alternative as it involves delivering the muscle relaxant directly to the
ureter. When the stones pass through the
narrow tube, cramps and inflammation in the ureter occur, causing most of the
pain. Therefore, if the muscles around the tube are relaxed, the passage could
Lee, who had joined MIT's Health Sciences and Technology program, became
interested in the field of kidney stone treatment when discussing possible
thesis options with Cima. "If you look at
how kidney stones are treated today, it hasn't really changed since about 1980,
and there's a pretty substantial amount of evidence that the drugs given don't
work very well. The volume of how many people this could potentially help is
Drug Selection Process
step involved identifying drugs that would work best when delivered directly to
the ureter. 18 drugs used in treating conditions like high blood
chosen and exposed to human ureteral cells that were grown in a lab dish. This
allowed for measuring the extent to which the drugs were able to relax the
smooth muscle cells. The hypothesis was
that the level of relaxation would be higher when the drugs were administered
directly to the ureter as opposed to taking them orally, which would also mean
minimizing harm to the rest of the body.
the selection of drugs, Cima said, "We
found several drugs that had the effect that we expected, and in every case, we
found that the concentrations required to be effective were more than would be
safe if given systemically."
computational processing was then used by the team to analyze individually, the
relaxation responses of close to 1 billion cells following exposure to the
drugs. Two drugs in particular were found to be very effective and worked even
better when administered together - Nifedipine,
which is a calcium channel blocker used in treating high blood pressure
and ROCK (rho kinase) inhibitor
, used in
combination in various doses was tested by the research team, in ureters
removed from pigs and demonstrated that the occurrence and span of contractions
of the ureter could be drastically reduced. Tests done on live pigs showed that
the ureteral contractions were nearly eliminated by the treatment.
the extent of the muscle-relaxing effects, knowing how long they would last and
the amount of relaxation required to accelerate the stone passage would require
further studies, the research team said. A startup company, Fluidity Medicine,
is also being
launched by them where the technology for possible testing in humans could be
could also be used for relaxing the ureter when doctors attempt to insert a
ureteral stent. Other instruments like endoscopes
could also be placed in the ureter
using the technique. Lee summarized, "The
platform pairs drug delivery to the ureter. We are eager to first target muscle
relaxation, and as offshoots of that, we have kidney stones, ureteral stents,
and endoscopic surgery. We have a bunch of other urological indications that
would go through different developmental pathways but can all be hit and all
have meaningful patient populations." Reference :
- New treatment could ease the passage of kidney stones - (http://news.mit.edu/2019/treatment-kidney-stone-passing-easier-1202)