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Daily News: Disease

Stanford, UCSF flexing muscles against arthritis


1SF

08-28-13

Aug. 28--The same affliction that causes Dr. Larry Morrill to suffer can affect humans of any age, but also dogs, cats and even, possibly, according to one study published last year, the pliosaur, a marine mammal of the Jurassic and Cretaceous periods.

Morrill, 73, has arthritis. More specifically, he has osteoarthritis, one of more than 100 forms of arthritis, a class of musculoskeletal disorders that, most basically defined, involves the often painful inflammation of the body's joints.

It is a family of diseases with extensive scope and significant burden. To wit, a sampling of statistics: At least 50 million U.S. adults have some form of arthritis, and that number will climb to 67 million by 2030, according to the Centers for Disease Control and Prevention.

In California, where more than 5 million adults have arthritis, the total economic impact of the disease was an estimated $12.1 billion in 2003, the last year for which there are estimates. It is the leading cause of disability in the country.

So many unknowns

Arthritis can be extraordinarily debilitating, turning life into something chronically painful and in some cases severely limiting physical mobility. For Morrill, a Menlo Park orthodontist, the pain was a persistent background to daily life that made tennis impossible, traveling a challenge, and taking the stairs at work agonizing.

Yet for all the recent advancements in treatment and understanding of these diseases, wide gaps in knowledge still exist.

"We are humbled by how little we know despite some tremendous research that has gone on," said Dr. Mark Genovese, a Stanford rheumatologist. "The more we learn, the more we realize we don't know. It tuns out that the disease is not so simple."

Genovese is among the 20 or so doctors and scientific investigators involved in a new partnership between Stanford and UCSF seeking to invest much muscle (and money) in hopes of increasing the pace of arthritis research.

Many puzzles face scientists who research these diseases.

For example, several therapies exist for treating rheumatoid arthritis, one of the most prevalent forms, but identifying which therapy might work with a particular individual can be a long process of trial and error -- during which the patient continues to suffer and the disease can progress. Finding a treatment can be even more difficult if the case is not diagnosed early.

And for osteoarthritis, the most common form, there is no form of treatment other than pain management and, when the disease becomes too painful or limiting, joint replacement.

The underlying cause of most forms of arthritis is largely unclear. It is also uncertain why some people develop it while others don't, and why it occurs in some parts of the body but not others.

The new center, named the Northern California Arthritis Foundation Center of Excellence, is largely focused on rheumatoid and osteoarthritis. Other common arthritic diseases include fibromyalgia, gout and lupus.

Osteoarthritis, which Morrill has, is a progressive degenerative joint disease. It usually develops gradually, as cartilage in the joint begins to break down. That cartilage serves to cushion bones to make walking, for instance, usually an easy and pain-free experience. As it breaks down, imagine that as you walk, the bones in your knee rub against each other. In other words: ouch.

Injuries put patient at risk

Though the cause is unknown, risk factors for the disease include age, weight, genetics and injury or repetitive stress. Morrill said he believes it was his career on the high school football team that caused his arthritis -- knee injuries were a regular occurrence. It most often occurs in weight-bearing joints such as the knees or hips.

Morrill has been involved in a study through the new center hoping to develop a drug therapy to treat the disease.

The study, led by Genovese, gave patients with osteoarthritis of the knees two well-known generic medications. Patients were then followed for 16 weeks and examined to see if the drug combination resulted in any functional improvement as well as changes to the levels of inflammation in their cartilage.

Trying to ease pain

Morrill, who has remained on the drugs, said his pain has been greatly reduced since participating in the research. The study, which is scheduled for publication this fall, was rooted in animal models of the disease created by Dr. William Robinson, another Stanford rheumatologist and a co-director of the center.

"Presently, all we can do is treat the pain until it becomes intolerable," Robinson said. "Many drug companies have tried to come up with a solution and, so far, failed."

This month, Ampio Pharmaceuticals, a Colorado company, announced that its experimental anti-inflammatory, Ampion, significantly reduced knee pain for patients in advanced clinical trials, though further trials are needed. Countless drugs to treat the underlying disease have failed in clinical trials.

A study published this month in the Journal of Bone and Joint Surgery found that, for now, a knee replacement might be the best bet for people with advanced osteoarthritis.

Rheumatoid arthritis, meanwhile, is an autoimmune disease in which the immune system mistakenly attacks the healthy cells in the membranes that line the joints, causing pain and, over time, degradation of the cartilage and bone. That inflammation can spread to other organs. Triggers, most doctors agree, involve some combination of genetic and environmental factors. It can occur in people of any age, including a form of the disease that affects children.

Several treatments are available, thanks to intensive research over the past 20 years. These include a class of disease-modifying antirheumatic drugs, called DMARDS, meant to stop inflammation, and biologic response modifiers that control the immune system to halt its attacks. Most people respond to some combinations of these drugs, although some don't.

"This is now a remarkable period of time. We now have a large array of effective therapies for RA," said Dr. John Imboden, chief of rheumatology at San Francisco General Hospital and co-director of the new center.

The challenge is often figuring out which treatment option will work.

Gauging effective therapies

To that end, scientists at Stanford and UCSF, like many others, are working to identify biomarkers that might allow doctors to predict which therapies a patient might respond to.

"Instead of the empirical approach, we'd have a much more rational approach to treatment," Imboden said.

The new center is examining some of the biggest problems facing the field, said Dr. John Hardin, director of osteoarthritis research for the Arthritis Foundation.

At the Stanford-UCSF center, which was established with the help of a $2 million grant from the Northern California chapter of the Arthritis Foundation, investigators from each university regularly meet to exchange ideas. Every project is co-led by scientists from each school. Among the center's lofty goals: explore how the disease develops, come up with new therapies to quell the disease, and regenerate damaged cartilage.

"We're nowhere near as sophisticated in treating (arthritis) as we should be," Genovese said.

Anti-inflammatories help

Morrill, the orthodontist, said he didn't realize how much pain he was in until it began to lessen.

"I was just suffering. I could take some Tylenol -- that was pretty much it," he said. "I sucked it up. That's what men do -- they suck it up."

In the past decade, the pain in his knees had gotten progressively worse. He recalled a vacation to Japan six years ago, during which his knees were so sore he could hardly walk.

"Every night at the hotel I had to go to the ice machine and get a bucket of ice for my knees," he said.

The anti-inflammatory drugs taken in Genovese's trial have made all the difference.

"I don't think I feel very much pain now," he said, "Or at least I don't really notice it."

Kristen V. Brown is a San Francisco Chronicle staff writer. E-mail: kbrown@sfchronicle.com Twitter: @kristenvbrown

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Copyright 1SF 2013

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