Bay Area firm at forefront of science seeking arthritis cure

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In his youth, Tim Landerville played center field for a Philadelphia Phillies minor league team, sprinting after fly balls in the grassy outfields he patrolled in the 1970s.

Now 67, the Santa Rosa man, who stands 6 feet 4 inches and weighs over 200 pounds, said he “can’t run at all” — hobbled by a pair of arthritic knees. Going downstairs is painful and walking through airports on business trips is an ordeal.

Landerville, who took acetaminophen and glucosamine for years, is now receiving more potent injections and contemplating surgical replacement of both knees.

A less-invasive and painful option to treat his advanced osteoarthritis would be welcome. “If it were true, I would jump at it,” he said. “Absolutely.”

One potential cure to a disease that afflicts 14 million Americans and costs $27 billion a year to treat is a compound code named UBX0101, the product of seven years of research at a Brisbane-based company, Unity Biotechnology, a startup focused on relieving the diseases of aging.

If it clears the rigorous testing process mandated by the government, UBX0101 would be the first widespread payoff from senescence, a branch of science that targets certain cells in the human body as the underlying cause of aging and the handful of related diseases that end life.

Osteoarthritis is not deadly, but it is a major discomfort for the elderly as well as people still in the prime of their lives. A successful treatment in a major joint such as the knee would likely forestall arthritis in other joints, including the hips and hands.

UBX0101 is now in human clinical trial with about 48 volunteers. Judith Campisi, a scientific founder and shareholder in Unity, called the drug a breakthrough in the search for a cure to “one of the most painful consequences of old age.”

Campisi, a pioneer in the science of senescence, is now at the Buck Institute for Research on Aging in Novato. Her work has proved that senescent cells, which reside in small numbers throughout the human body, secrete proteins that trigger inflammation and alter the function in neighboring cells, a prelude to fatal maladies, such as cancer, Alzheimer’s, heart disease and adult-onset diabetes.

Conversely, she also has showed that, senescent cells, which increase in number with age, also afford people a shield against cancer since they cannot divide.

She and Jan van Duersen, a professor at the Mayo Clinic in Rochester, Minnesota, found a way to genetically engineer mice so their senescent cells could be removed, a step that Van Duersen showed increased the rodents’ lifespan by 20 to 35 percent.

In another experiment, van Duersen compared two mice from the same litter, finding the one with no senescent cells sleek and healthy near the end of its life, while the other was bent, blind and crippled with a failing heart and kidneys.

Unity co-founder Nathaniel David, an inventor and entrepreneur, was impressed by their work, calling it the “coolest biology” he had ever seen. Unity, his fifth startup, was founded in 2011 with more than $300 million in funding, including investments by billionaires Jeff Bezos, founder of Amazon, and PayPal co-founder Peter Thiel.

David, a Harvard and UC Berkeley-trained molecular and cell biologist, sold two of his first four companies — one that produced a diabetes drug, the other a remedy for double chins — for well over $2 billion. His lone business whiff is a company that managed to make a crude oil substitute from algae but was thwarted when oil prices plummeted.

At an event last week at the Buck Institute celebrating 30 years of research on aging, David noted that the mouse with no senescent cells in van Duersen’s experiment was not only healthier than its sibling, but also retained the adventurous nature of a young rodent, signaling the potential advancements involved in further research into the subject.

There has never been a drug that makes people “want to go camping or take up a musical instrument,” he said.

Osteoarthritis, known as a “wear and tear” disease, involves a progressive breakdown of cartilage, the firm, rubbery material that covers and cushions the end of bones in the knees and other joints. When bone begins rubbing against bone, the pain typically drives people to a surgical replacement of the hip or knee.

Considered a disease of aging, osteoarthritis now occurs equally among people 45 to 64 and 65 and older, with about 6 million people in each cohort, according to the Arthritis Foundation.

Dr. Ty Affleck, medical director of Santa Rosa Sports and Family Medicine, said that over-the-counter medications like ibuprofen help people with mild arthritic knee pain. For more advanced cases there are steroid injections that calm the inflammation but “don’t fix anything,” he said.

More expensive and longer- lasting are injections of hyaluronic acid, commonly known as “chicken juice” for its origin in rooster combs. Landerville saw Affleck on Friday for the third injection of the substance into his right knee, anticipating several months of relief.

“A ton of stuff is being thrown at knee arthritis right now,” Affleck said, and people are “paying thousands of dollars” for various therapies, including injections of sugar, protein-rich plasma and stem cells, but there is no cure.

The only permanent relief is knee replacement surgery, which costs about $20,000 and is performed on about 700,000 people a year, according to the Arthritis Foundation.

UBX0101, injected into arthritis- ravaged knees, is expected to eradicate the senescent cells, halt the loss of cartilage and eliminate the need for surgery, Campisi said. Tests on mice and human tissue in labs indicate it will also enable stem cells in people’s knees to regenerate lost cartilage.

Ailing knees were chosen for the first government-approved trial of Unity’s compound because it will remain in the joint. The Food and Drug Administration is leery of drug safety trials that spread an untested substance throughout the body, Campisi said.

Next year, the company plans to test a different compound, UBX1967, in the eyeball as a possible senescent cure for glaucoma, a leading cause of blindness among elders.

Unity can’t say when the remedy for failing knees might go on the market, and Landerville, the ex-ballplayer plans on replacements.

“I’ve had enough,” he said. “Having knees like this is no fun.”

You can reach Staff Writer Guy Kovner at 707-521-5457 or

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