DnaJP1 - Rheumatoid arthritis aid may come from UA

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Rheumatoid arthritis aid may come from UA: Researchers upbeat that synthetic

peptide will offer more relief

http://www.tucsoncitizen.com/daily/local/77417.php

A University of Arizona researcher's discovery may help millions of people

who suffer from crippling rheumatoid arthritis.

Dr. Salvatore Albani is working on a safer, better and less expensive way to

battle arthritis, the nation's leading cause of disability.

His discovery - a computer-designed peptide called dnaJP1 - could change the

way physicians treat rheumatoid arthritis - the most debilitating type of

arthritis that painfully inhibits joint function - and cut down potentially

harmful treatment side effects patients can face.

Albani, director of UA's Arizona Arthritis Center, likened conventional

treatments using drugs called immunosuppressants and biologics to suppress

the effects of rheumatoid arthritis - RA - to a civil war where many good,

innocent people are killed in the course of battle.

RA is an autoimmune disease, where the body's immune system, which normally

protects the body from disease and infection, itself generates inflammation

in joints, he said.

" It's like a civil war where the body turns against the body. The immune

system turns against the body, " Albani said.

Albani is working on an immune modulation therapy that " re-educates " the

immune system to avoid causing inflammation, joint swelling and pain.

" We detect a mechanism which itself sustains inflammation; it perpetuates

the inflammation, " he said. " We break the loop. We re-educate the system to

control those mechanisms of inflammation that generate the damage to the

body. "

Arthritis is the leading cause of disability in the United States, according

to the Centers for Disease Control and Prevention. Osteoarthritis, a

degenerative joint disease, is the most common form of arthritis, but RA is

responsible for the vast majority of disabilities related to the disease.

Arthritis and other rheumatic conditions, such as fibromyalgia and bursitis,

cost $127.8 billion in the U.S. - including $2.3 billion in Arizona - in

medical expenses and lost earnings in 2003, according to the CDC.

Biologic drugs designed to suppress the immune system have been used for 10

years to try to overcome the crippling effects of RA, said Dr. Berchman

Austin Vaz, assistant professor of medicine at University Medical Center.

About 30 percent to 40 percent of RA patients do not respond to biologics

and may benefit from the immune modulation therapy Albani is pursuing, Vaz

said.

" There are still a substantial number we could benefit with the new

therapies, " he said.

The existing treatments can wipe out more than just the problem at hand,

including the body's ability to protect itself from infection and disease.

" It is like going in with a tank. You kill them all; you also kill good,

useful people, " Albani said.

Drugs that suppress the immune system can also pose side effects and open

the patient to other diseases, Vaz said.

" The major risk is infections. You are suppressing the immune system with

these medications, " he said.

A big local threat is valley fever, he said. Valley fever - or

Coccidioidomycosis - is a fungal pneumonia with no cure that primarily

strikes people in desert areas of southern Arizona and the San Joaquin

Valley in California.

Preliminary results from a three-year study show that people taking

biologics have a greater incidence of valley fever, Vaz said. His patients

taking biologics have annual chest X-rays and blood tests as a precaution,

he said.

Patients taking biologics are asked to seek medical care immediately if they

have a fever or believe they may be developing an infection, he said.

Tucsonan Hard has seen RA gradually take away his athleticism and

mobility since the 1970s.

Hard, a retired bank executive, is taking a biologic drug that successfully

treats the disease, but he must still remain extremely wary of the threat of

infection.

When he feels the onset of a fever or infection, he checks in with his

doctor, who gives him antibiotics when needed.

And any time he travels, Hard must take antibiotics with him, just in case

something develops.

While biologics have been successful in giving patients their lives back,

Vaz said, " The risk is low, but it is a real risk. "

After researching the mechanism of how arthritis works, Albani came up with

a new, safer way to fight the disease using a new type of biologic drug

called dnaJP1. " We shift from suppression to tolerance, " he said. " We teach

the immune system to be tolerant of its own body. "

The new treatment, which consists of a daily oral dose of the

computer-designed synthetic peptide dnaJP1, acts as a natural dimmer on the

immune system, which typically goes into overdrive when it starts producing

RA inflammation. A peptide is a molecule made up of two or more amino acids

and dnaJP1 has 15 amino acids.

Oral ingestion of dnaJP1 allows the body to tolerate the peptide and trigger

the dimming response to break the loop of inflammation in the immune system,

he said. Some biologics are taken by needle, Albani said.

DnaJP1 has undergone Phase 1 and Phase 2 clinical trials.

" The drug was proven safe, and showed encouraging signs of clinical efficacy

while proving its ability to reverse the inflammatory response in the

patient, " he said.

Ten area residents were among the 160 people from around the nation

participating in the Phase 2 clinical trial, said Dr. Posever,

rheumatologist at the Phoenix Indian Medical Center.

Posever, who led the local seven-month group study, said participants

receiving dnaJP1 benefited.

" Many of them did quite well as time went forward, " Posever said. " As for

side effects, it was just about nil. It won't do anything to suppress the

immune response against a cold or the flu or an infection. It doesn't blunt

the body's response to foreign invaders. "

Testing so far has been successful, but the U.S. Food and Drug

administration requires that it be tested on more than 1,000 patients before

it is approved for market, Albani said.

" I can't say this is something to give to patients tomorrow, " he said. " It

needs some more research. "

The project has been academic-based so far, with funding from the National

Institutes of Health and other organizations, but funding from sponsors such

as major drug companies may be needed to get more testing done and to market

the drug, he said.

It will likely be five years before FDA approval is granted and doctors can

prescribe the medication, assuming corporate interest is found to sustain

continued development, Albani said.

RA drugs can cost up to $15,000 a year, but dnaJP1 may be significantly

less, offering savings to consumers, Albani said.

" This could open the treatment to many more people, " Vaz said. " The more

medications we have, the more the cost will come down. "

The drug will be a pill taken once a day, and at some point RA sufferers may

be able to discontinue the medication, Albani said.

" The peptide's effect may be long-lasting and induce tolerance, " he said.

It might also be used in conjunction with existing RA drugs for optimal

treatment, he said.

DnaJP1 takes time to work, and existing drugs can also be used initially

until the peptide kicks in.