Salvatore Albani, M.D., Ph.D, professor of medicine andpediatrics and Director of the Translational Research Unit of theClinical Investigation Institute (CII) at the UCSD School of Medicine,recently presented a summary of the findings at the “Frontiers ofClinical Investigation Symposium.” The symposium, sponsored by the CIIand Nature Medicine, was held in La Jolla, California in September.
Thenew drug, dnaJP1, is a peptide derived from a naturally occurringprotein, dnaJ, which generates inflammation in RA patients, whoseinflammatory-control mechanisms are impaired. The impairment causes thebody’s T cells – which trigger inflammation to kill and clear foreignpathogens in the body – to attack the body’s own tissues.
“Inessence, we re-educated the immune system T cells to be tolerant of thednaJP1 amino acid sequence, which would usually contribute toinflammation in rheumatoid arthritis patients,” Albani said.
DnaJP1works by resetting the ability of the patient’s immune system totolerate dnaJ, thus transforming a potentially damaging trigger into atool 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 orforeign. Much as food is ingested into the body and not rejected, thebody tolerates dnaJP1.
Current medications for treating RA rangefrom anti-inflammatory drugs, such as aspirin, to corticosteroids andmedicines that alleviate symptoms by suppressing or killing the body’simmune response, basically crippling the body’s ability to defenditself against other infectious diseases or cancer.
“Such drugsare costly, have potentially dangerous side effects and areinconvenient to administer,” Albani said. “Our drug leaves thepatient’s natural immune responses intact. This differs profoundly fromwhat is currently available to patients.”
DnaJP1 was foundeffective in a double-blind, placebo-controlled trial sponsored by theNational Institutes of Health, which took place between 2000 and 2005and involved 160 patients enrolled in centers nationwide includingUCSD, Stanford University, Johns Hopkins University, the Mayo Clinic,and Virginia Mason Medical Center in Seattle. The technology wasdeveloped at UCSD and has been licensed for further development toAndroclus Therapeutics, a biotechnology company located in San Diegoand Milan, Italy. Dr. Albani is one of the company’s co-founders.
Patientsreceived 25mg of dnaJP1 daily by mouth for six months, and thetreatment was found to be safe and well-tolerated. When compared with aplacebo, patients in the treatment group experienced lessening ofsymptoms such as swollen joints, tenderness, pain and decreasedmobility. Improvement was particularly significant at the follow upvisits, indicating a lasting effect of the drug. Efficacy wasquantified in data generated from physicians, patients andlaboratories, measuring improvement according to standards set by theAmerican College of Rheumatology (ACR) from the beginning to laterpoints in the trial. For instance, “ACR 20” indicates a 20% improvementin standardized symptoms. ACR 20 response was in the 50-55% range; ACR50 in the 30-40% range; and ACR 70 in the 15-20% range of patientscompleting the trial.
Rheumatoid arthritis, or inflammation ofthe joints, is a chronic, painful disease affecting one percent of theU.S. population, or more than 2 million people. It occurs three timesmore often in women than men, targeting people of every age. Thecondition simultaneously strikes joints on both sides of the body, suchas 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 thecurrent available drugs pose risks to patients, the first two trials ofdnaJP1 have not raised any significant safety concerns and offer animproved treatment option for patients with rheumatoid arthritis,” saidAlbani. The next step, according to Albani, is to get approval andfunding to move into Phase III clinical trials.
“This is a veryexciting and novel therapeutic approach, which holds the promise to bean entirely new type of immunomodulatory drug – one that can shape apatient’s immune system, rather than suppressing it,” said Gary S.Firestein, M.D., Director of CII (http://cii.ucsd.edu/), which providesUCSD faculty with an infrastructure to support the translation offundamental biology into novel therapeutic interventions. “It is alsoan Institute success story because it represents a true ‘bench tobedside’ research model.”
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