New approach to treating osteoarthritis advances

Date:
August 10, 2020
Source:
NYU Langone Health / NYU School of Medicine
Summary:
Injections of a natural 'energy' molecule prompted regrowth of
almost half of the cartilage lost with aging in knees, a new study
in rodents shows.



FULL STORY ==========================================================================
The study results revolve around the long-established idea that machines
within animal and human cells turn the sugars, fats, and proteins we
eat into energy used by the body's millions of cells. The molecule
most used to store that energy is called adenosine triphosphate, or
ATP. Along with this central role in metabolism, adenosine also helps
signal other cells and serves as a building block of genetic material,
and so is central to the growth of human tissue.


========================================================================== Previous research had shown that maintaining supplies of adenosine, known
to nourish the chondrocyte cells that make cartilage, also prevented osteoarthritis in similar animal models of the disease.

In the new NYU Grossman School of Medicine-led study, researchers injected adenosine into the joints of rodents whose limbs had been damaged by inflammation resulting from either traumatic injury, such as a torn
ligament, or from massive weight gain placing pressure on joints. The biological damage in these cases is similar, researchers say, to that
sustained in human osteoarthritis.

Publishing online in the journal Scientific Reports on Aug. 10, the study rodents received eight weekly injections of adenosine, which prompted
regrowth rates of cartilage tissue between 50 percent and 35 percent as measured by standard laboratory scores.

"Our latest study shows that replenishing adenosine stores by injection
works well as a treatment for osteoarthritis in animal models of the
disease, and with no apparent side effects," says lead study author
Carmen Corciulo, PhD, a postdoctoral fellow at NYU Langone.

Corciulo says it is too soon to use this experimental model as a therapy
in people. Clinical trials must await a test drug that can be safely
stored for days if not weeks, and experiments in larger mammals.



========================================================================== Study senior investigator Bruce Cronstein, MD, the Dr. Paul R. Esserman Professor of Medicine at NYU Langone Health, says the team's research is important because the few existing drug therapies for osteoarthritis,
such as acetaminophen and COX-2 inhibitor drugs, including naproxen
and ibuprofen, only numb joint pain, or like hyaluronic acid, just
lubricate its tissues. None stall disease progression or reverse the
damage. Painkillers, such as opioids, are often prescribed, but are also
highly addictive, he cautions.

"People with osteoarthritis desperately need more treatment options
with fewer side effects, and our research advances that effort,"
says Cronstein, who also serves as the director of the Clinical and Translational Science Institute (CTSI). He noted that other experimental medications are being developed elsewhere, including parathyroid hormone
to stimulate bone growth, WNT inhibitor drugs to block the bone and
cartilage degradation, and growth factor chemicals to promote cartilage
growth.

Cronstein, Corciulo, and NYU Grossman School of Medicine have a patent application pending for the use of adenosine and other agents that help
with its binding to chondrocytes, called A2A receptor agonists, for the treatment of osteoarthritis.

Among the study's other key findings was that a cell-signaling pathway,
known as transforming growth factor beta (TGF-beta) and involved in many
forms of tissue growth, death and differentiation, was highly active
in cartilage tissue damaged by osteoarthritis, as well as in cartilage
tissue undergoing repair after being treated with adenosine. Additional
testing in lab-grown chondrocytes from people with osteoarthritis showed different chemical profiles of TGF-beta signaling during breakdown than
during growth, providing the first evidence that the pathway switched
function in the presence of adenosine (from assisting in cartilage
breakdown to encouraging its repair.) Developing treatments to halt or
slow the disease is important, Cronstein says, because well over 100
million people worldwide are estimated to have osteoarthritis, which
is tied to aging, especially in women. This figure, he says, is only
expected to grow as more people live longer and obesity rates climb.

"Right now, the only way to stop osteoarthritis is to have affected joints surgically replaced, which not only comes with pain and risk of infection,
but is also quite costly," says Cronstein. "If new therapies can delay
or prevent disease onset and progression, then fewer joint replacements
will save people from a lot of pain and expense." The study was funded
by National Institutes of Health grants R01 AR056672 and R01 AR068593,
NYU-HHC Clinical and Translational Science Institute grant UL1 TR000038,
and the Arthritis Foundation.


========================================================================== Story Source: Materials provided by NYU_Langone_Health_/_NYU_School_of_Medicine. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Carmen Corciulo, Cristina M. Castro, Thomas Coughlin, Samson
Jacob, Zhu
Li, David Fenyo", Daniel B. Rifkin, Oran D. Kennedy, Bruce
Neil Cronstein. Intraarticular injection of liposomal adenosine
reduces cartilage damage in established murine and rat models
of osteoarthritis.

Scientific Reports, 2020; 10 (1) DOI: 10.1038/s41598-020-68302-w ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200810103257.htm

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