Is Gene Therapy Next for Treatment of Autoimmune Diseases?

Patient Expert
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Chemotherapy for lupus. Biologics for Crohn’s disease. Stem cell transplants for scleroderma. Gene therapy for rheumatoid arthritis?

According to Dr. Edward Lally, director of rheumatology at Brown University’s Warren Alpert Medical School, rheumatologists and immunologists get a lot of their strategies from their oncology colleagues.

“We both look at disease with cellular proliferation. Ours results in inflammation; theirs results in cancer,” he says.

While the specialists use similar tactics to dampen immune response, Lally says rheumatologists use monotherapy to inhibit cells or cell products that are responsible for inflammation.

The idea behind traditional cancer immunotherapy is to kill cells that are malignant,” he says. “We don’t use combination therapy the way oncologists do.”

But for gene therapy, widely considered to be the new frontier for cancer treatment, it only takes one patient-specific dose — a life-changing one, at that.

Last month, a Food and Drug Administration panel unanimously endorsed gene therapy treatment for B-cell acute lymphoblastic leukemia, the most common childhood cancer. The treatment could be approved for the U.S. market this year.

In clinical trials, a single dose of drug company Novartis’s gene therapy treatment — which gives a patient’s own cells the power to fight cancer through a disabled form of HIV — has resulted is long remissions and, possibly, cures. Novartis is also running gene therapy trials involving other cancers, including multiple myeloma.

If it works for cancer, could it work for rheumatoid arthritis and other autoimmune diseases with cellular proliferation?

“With oncologists setting the tone with gene therapy, it’s logical that immunologists and rheumatologists are picking up the ball,” says Lally.

A cure from within

Arthrogen, a Netherlands-based company, is in the process of recruiting patients for a small, early stage safety study of gene therapy treatment for patients with rheumatoid arthritis. A Dutch study will involve 12 patients with RA in the finger joints. This fall, a second Canadian study will recruit 15 patients with RA in the wrist.

Study participants will receive a single dose of gene therapy, which involves a virus delivered directly into the joints. Arthrogen’s researchers will then track them for the first six months, then again for four-and-a-half years.

“Our hope is that a single treatment will deliver a possibility for the body to start producing an anti-inflammatory protein when needed,” says Arthrogen CEO Robert Jan Lamers.

The company launched in 2005 when University of Amsterdam professor of medicine Paul-Peter began searching in earnest for a treatment that, unlike most modern-day drugs for autoimmune diseases, was localized instead of systemic, decreasing the potential for off-target side effects.

“He thought: ‘How can we get something on the right spot that has a long-lasting effect and only switches on when it’s needed and off when it’s not?’” Lamers says. “This is still in the beginning, but it is possibly something completely different than the current standard of care.”

Lamers is careful to manage expectations. Arthrogen’s gene therapy studies on animal models reduced inflammation for extended periods of time; the forthcoming clinical trials will test whether these gene therapy treatments are safe for humans.

Arthrogen isn’t the first company to study gene therapy treatment for patients with RA. In 2007, the Seattle-based Targeted Genetics launched a nationwide trial studying its effectiveness. But when a 36-year-old participant died in the midst of the study, its progress stalled. Her death was eventually attributed to a fungal infection that wreaked havoc on her weakened immune system, not the gene therapy. Targeted Genetics has since rebranded as AmpliPhi Biosciences, moved its headquarters to London and switched its focus to bacteriophage therapies.

Despite the risk, Lamers says he believes the field is making a lot of progress.

“We feel that gene therapy, or other advanced therapies, are regenerative and we feel that a single treatment is something to aim for,” he says.

The company is also looking at gene therapy options for adjacent arthritic conditions.

“We are looking, even beyond that, to other autoimmune indications,” he says. “We talk with a lot of patients — some rather desperate patients — so we try to do it as fast as we can. We work as much hours as we can, but it can be a very slow process.”

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