New Rheumatoid Arthritis Drug Developed At UCSD Promises Improved
Treatment Options
Researchers at the University of California, San Diego (UCSD) School
of Medicine have announced successful completion of Phase II clinical
trials of a novel drug for the treatment of rheumatoid arthritis (RA),
one that works without suppressing the patient’s immune system.

The new drug, dnaJP1, is a peptide derived from a naturally occurring
protein, dnaJ, which generates inflammation in RA patients, whose
inflammatory-control mechanisms are impaired. The impairment causes
the body’s T cells – which trigger inflammation to kill and clear
foreign pathogens in the body – to attack the body’s own tissues.

“In essence, we re-educated the immune system T cells to be tolerant
of the dnaJP1 amino acid sequence, which would usually contribute to
inflammation in rheumatoid arthritis patients,” Albani said.

DnaJP1 works by resetting the ability of the patient’s immune system
to tolerate dnaJ, thus transforming a potentially damaging trigger
into a tool for controlling the disease. Oral ingestion of dnaJP1 is
key, because the mucosal immune system found in the gut has the
ability to “teach” the body to view a protein as one that isn’t
dangerous or foreign. Much as food is ingested into the body and not
rejected, the body tolerates dnaJP1.

Current medications for treating RA range from anti-inflammatory
drugs, such as aspirin, to corticosteroids and medicines that
alleviate symptoms by suppressing or killing the body’s immune
response, basically crippling the body’s ability to defend itself
against other infectious diseases or cancer.

“Such drugs are costly, have potentially dangerous side effects and
are inconvenient to administer,” Albani said. “Our drug leaves the
patient’s natural immune responses intact. This differs profoundly
from what is currently available to patients.”

DnaJP1 was found effective in a double-blind, placebo-controlled trial
sponsored by the National Institutes of Health, which took place
between 2000 and 2005 and involved 160 patients enrolled in centers
nationwide including UCSD, Stanford University, Johns Hopkins
University, the Mayo Clinic, and Virginia Mason Medical Center in
Seattle. The technology was developed at UCSD and has been licensed
for further development to Androclus Therapeutics, a biotechnology
company located in San Diego and Milan, Italy. Dr. Albani is one of
the company’s co-founders.

Patients received 25mg of dnaJP1 daily by mouth for six months, and
the treatment was found to be safe and well-tolerated. When compared
with a placebo, patients in the treatment group experienced lessening
of symptoms such as swollen joints, tenderness, pain and decreased
mobility. Improvement was particularly significant at the follow up
visits, indicating a lasting effect of the drug. Efficacy was
quantified in data generated from physicians, patients and
laboratories, measuring improvement according to standards set by the
American College of Rheumatology (ACR) from the beginning to later
points in the trial. For instance, “ACR 20” indicates a 20%
improvement in standardized symptoms. ACR 20 response was in the
50-55% range; ACR 50 in the 30-40% range; and ACR 70 in the 15-20%
range of patients completing the trial.

Rheumatoid arthritis, or inflammation of the joints, is a chronic,
painful disease affecting one percent of the U.S. population, or more
than 2 million people. It occurs three times more often in women than
men, targeting people of every age. The condition simultaneously
strikes joints on both sides of the body, such as the hands or feet or
knees but can also affect the skin, eyes, lungs, heart, blood, nerves
or kidneys. It is an incurable disease, with most therapies focusing
on symptom relief.

“Although the current available drugs pose risks to patients, the
first two trials of dnaJP1 have not raised any significant safety
concerns and offer an improved treatment option for patients with
rheumatoid arthritis,” said Albani. The next step, according to
Albani, is to get approval and funding to move into Phase III clinical
trials.

“This is a very exciting and novel therapeutic approach, which holds
the promise to be an entirely new type of immunomodulatory drug – one
that can shape a patient’s immune system, rather than suppressing it,”
said Gary S. Firestein, M.D., Director of CII (http://cii.ucsd.edu/),
which provides UCSD faculty with an infrastructure to support the
translation of fundamental biology into novel therapeutic
interventions. “It is also an Institute success story because it
represents a true ‘bench to bedside’ research model.”

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