Gene Therapy for Human Arthritis

On many occasions on this blog I have urged us to seriously ponder, and prepare for, the greatest challenge facing humanity this century--- tackling the health challenges facing aging populations. This is a challenge that human societies have never had to tackle before.

Before the 19th century life expectancy in the world was below 30 years. Today it is 67 and expected to rise to 75 by 2050.

To get a sense of the human toll senescence will reap in the years to come just consider arthritis along. Arthritis covers over 100 different conditions. Here are some facts from the Arthritis Foundation:

Number of Americans with arthritis or chronic joint symptoms:

1985 - 35 million
1990 - 37.9 million
1998 - nearly 43 million (1 in 6 people)
2006 – 46 million (nearly 1 in 5 adults)
Arthritis is one of the most prevalent chronic health problems and the nation’s leading cause of disability among Americans over age 15.
Arthritis is second only to heart disease as a cause of work disability.
Arthritis limits everyday activities such as walking, dressing and bathing for more than 7 million Americans.
Arthritis results in 39 million physician visits and more than a half million hospitalizations.
Costs to the U.S. economy totals $128 billion annually.
Arthritis affects people in all age groups including nearly 300,000 children.
Baby boomers are now at prime risk. More than half those affected are under age 65.
Half of those Americans with arthritis don’t think anything can be done to help them.
Arthritis refers to more than 100 different diseases that affect areas in or around joints.
Arthritis strikes women more often than men.

The health (e.g. pain and suffering) and economic toll of arthritis is staggering. The latest issue of Human Gene Therapy offers some hope to those who currenty suffer arthritis (and those bound to in the years to come). It provides some reason for optimism that gene therapy for arthritis might offer some therapeutic benefit to those who suffer from arthritis. Here is the abstract:

This paper provides the first evidence of a clinical response to gene therapy in human arthritis. Two subjects with rheumatoid arthritis received ex vivo, intraarticular delivery of human interleukin-1 receptor antagonist (IL-1Ra) cDNA. To achieve this, autologous synovial fibroblasts were transduced with a retrovirus, MFG-IRAP, carrying IL-1Ra as the transgene, or remained as untransduced controls. Symptomatic metacarpophalangeal (MCP) joints were injected with control or transduced cells. Joints were clinically evaluated on the basis of pain; the circumference of MCP joint 1 was also measured. After 4 weeks, joints underwent surgical synovectomy. There were no adverse events in either subject. The first subject responded dramatically to gene transfer, with a marked and rapid reduction in pain and swelling that lasted for the entire 4 weeks of the study. Remarkably, joints receiving IL-1Ra cDNA were protected from flares that occurred during the study period. Analysis of RNA recovered after synovectomy revealed enhanced expression of IL-1Ra and reduced expression of matrix metalloproteinase-3 and IL-1β. The second subject also responded with reduced pain and swelling. Thus, gene transfer to human, rheumatoid joints can be accomplished safely to produce clinical benefit, at least in the short term. Using this ex vivo procedure, the transgene persisted within the joint for at least 1 month. Further clinical studies are warranted.

Cheers,
Colin