New Injectable Gel Shows Promise for Treating
Millions with Arthritis
Half of senior citizens – aged 65 and over – suffer
with arthritis, one of most common causes of disability
potentially new way to treat arthritis - new gel (red, with
yellow rectangles representing encapsulated medicine) is
injected into an arthritic joint. There enzymes (black image)
associated with arthritis break down the biodegradable gel,
releasing the medicine. Courtesy: Praveen Vemula, Karp lab, BWH
April 13, 2011 - Some 25
million people in the U.S. suffer from rheumatoid arthritis or its
cousin osteoarthritis, diseases characterized by often debilitating pain
in the joints. At least half of all senior citizens suffer with some
form of arthritis. Now researchers at Brigham and Women’s Hospital (BWH)
report an injectable gel that could be a key to future treatment these
Among its advantages, the gel
could allow the targeted release of medicine at an affected joint, and
could dispense that medicine on demand in response to enzymes associated
with arthritic flare-ups.
“We think that this platform
could be useful for multiple medical applications including the
localized treatment of cancer, ocular disease, and cardiovascular
disease,” said Jeffrey Karp, leader of the research and co-director of
the Center for Regenerative Therapeutics at BWH.
Karp will present the findings
April 15 at the annual meeting of the Society for Biomaterials (SFB) as
winning the coveted SFB Young Investigator Award for this work. The
work was also reported by Karp and colleagues in the May 2011 issue of
the Journal of Biomedical Materials Research (JBMR): Part A, and is
currently available on the journal’s website.
Arthritis is a good example of
a disease that attacks specific parts of the body. Conventional
treatments for it, however, largely involve drugs taken orally. Not only
do these take a while (often weeks) to exert their effects, they can
have additional side effects. That is because the drug is dispersed
throughout the body, not just at the affected joint. Further, high
concentrations of the drug are necessary to deliver enough to the
affected joint, which runs the risk of toxicity.
“There are many instances
where we would like to deliver drugs to a specific location, but it’s
very challenging to do so without encountering major barriers,” says
Karp, who also holds appointments through Harvard Medical School (HMS),
Harvard Stem Cell Institute (HSCI), and the Harvard-MIT Division of
Health Sciences and Technology (HST).
For example, you could inject
a drug into the target area, but it won’t last long--only minutes to
hours--because it is removed by the body’s highly efficient lymphatic
system. What about implantable drug-delivery devices? Most of these are
composed of stiff materials that in a dynamic environment like a joint
can rub and cause inflammation on their own. Further, most of these
devices release medicine continuously--even when it’s not needed.
Arthritis, for example, occurs in cycles characterized by flare-ups then
Two of the researchers stand next to a
graphic describing their approach - Praveen Kumar Vemula of BWH
and Jeffrey Karp, co-director of the Center for Regenerative
Therapeutics at BWH. Photo by Donna Coveney
Toward the Holy Grail
“The Holy Grail of drug
delivery is an autonomous system that [meters] the amount of drug
released in response to a biological stimulus, ensuring that the drug is
released only when needed at a therapeutically relevant concentration,”
Karp and colleagues write in JBMR. His coauthors are Praveen Kumar
Vemula, Nathaniel Campbell, and Abdullah Syed of BWH, HMS and HSCI; Eric
Boilard (now at Université Laval), Melaku Muluneh, and David Weitz of
Harvard University; and David Lee of BWH, currently at Novartis. Karp
notes the key involvement of Lee, a doctor who is “treating patients
with the problem we’re trying to solve.”
The researchers tackled the
problem by first determining the key criteria for a successful locally
administered arthritis treatment. In addition to having the ability to
release drug on demand, for example, the delivery vehicle should be
injectable through a small needle and allow high concentrations of the
drug. The team ultimately determined that an injectable gel seemed most
Next step: what would the gel
be made of? To cut the time involved in bringing a new technology to
market, the team focused only on materials already designated by the
Food and Drug Administration as being generally recognized as safe
(GRAS) for use in humans.
Ultimately, they discovered a
GRAS material that could be coaxed into self-assembling into a
drug-containing gel. “The beauty of self-assembly is that whatever
exists in solution during the assembly process--in this case, a
drug--becomes entrapped,” says Vemula, first author of the paper, who
also has an appointment at HST.
They further expected that the
same material would disassemble, releasing its drug payload, when
exposed to the enzymes present during inflammations like those
associated with arthritis.
A series of experiments
confirmed this. For example, the team created a gel containing a dye as
a stand-in for a drug, then exposed it to enzymes associated with
arthritis. The drug was released. Further, the addition of agents that
inhibited the enzymes stopped the release, indicating that the gel “can
release encapsulated agents in an on-demand manner,” the researchers
write. Although the team has yet to test this in humans, they did find
that dye was also released in response to synovial fluid taken from
arthritic human joints.
Among other promising results,
the researchers found that gel injected into the healthy joints of mice
remained stable for at least two months. Further, the gel withstood wear
and tear representative of conditions in a moving joint.
Additional tests in mice are
underway. The technique has yet to be demonstrated in humans, but the
researchers write that it “should have broad implications for the
localized treatment of many…diseases” caused by the enzymatic
destruction of tissues.
The researchers have applied
for a patent on the work, which was sponsored by the Center for
Integration of Medicine and Innovative Technology (CIMIT) through the
U.S. Army and by the Harvard Catalyst Program.
Information about Arthritis
Here are some
Association of Rheumatology Health Professionals
1800 Century Place, Suite 250
Atlanta, GA 30345-4300
P.O. Box 7669
Atlanta, GA 30357-0669
or check the telephone directory for your local chapter www.arthritis.org
of Arthritis and Musculoskeletal and Skin Diseases
NIAMS Information Clearinghouse
1 AMS Circle
Bethesda, MD 20892-3675
1-301-565-2966 (TTY) www.niams.nih.gov
for Complementary and Alternative Medicine
P.O. Box 7923
Gaithersburg, MD 20898
1-866-464-3615 (TTY/toll-free) www.nccam.nih.gov
To get the NIA’s
exercise guide or Beware of Health Scams or for more information on
health and aging, contact:
a senior-friendly website from the National Institute on Aging and the
National Library of Medicine. This website has health information for
older adults. Special features make it simple to use. For example, you
can click on a button to have the text read out loud or to make the type
Institute on Aging
National Institutes of Health
U.S. Department of Health and Human Services
feel pain and stiffness in your body or have trouble moving around, you
might have arthritis. Most kinds of arthritis cause pain and swelling in
your joints. Joints are places where two bones meet, such as your elbow
or knee. Over time, a swollen joint can become severely damaged. Some
kinds of arthritis can also cause problems in your organs, such as your
eyes or skin.
type of arthritis,
osteoarthritis, is often
related to aging or to an injury. Other types occur when your immune
system, which normally protects your body from infection, attacks your
body's own tissues.
Rheumatoid arthritis is
the most common form of this kind of arthritis.
Juvenile rheumatoid arthritis
is a form of the disease that happens in children.
Infectious arthritis is
an infection that has spread from another part of the body to the joint.
arthritis (RA) is a form
of arthritis that causes pain, swelling, stiffness and loss of function
in your joints. It can affect any joint but is common in the wrist and
fingers. More women than men get rheumatoid arthritis. It often starts
between ages 25 and 55. You might have the disease for only a short
time, or symptoms might come and go. The severe form can last a
Rheumatoid arthritis is different from
the common arthritis that often comes with older age. RA can affect body
parts besides joints, such as your eyes, mouth and lungs. RA is an
which means the arthritis results from your immune system attacking your
body's own tissues.
knows what causes rheumatoid arthritis. Genes, environment and hormones
might contribute. Treatments include medicine, lifestyle changes and
surgery. These can slow or stop joint damage and reduce pain and
body's immune system protects you from disease and infection. But if you
have an autoimmune disease, your immune system attacks healthy cells in
your body by mistake. Autoimmune diseases can affect many parts of the
body. These diseases tend to run in families. Women - particularly
African-American, Hispanic-American, and Native-American women - have a
higher risk for some autoimmune diseases.
are more than 80 types of autoimmune diseases, and some have similar
symptoms. This makes it hard for your health care provider to know if
you really have one of these diseases, and if so, which one. Getting
diagnosed can be frustrating and stressful. In many people, the first
symptoms are being tired, muscle aches and low fever.
diseases may also have flare-ups, when they get worse, and remissions,
when they all but disappear. The diseases do not usually go away, but
symptoms can be treated.