Research For A Cure: Update from The National Institute of Health

I recently attended a lecture by Dr. John O’Shea, Chief of the Molecular Immunology and Inflammation Branch and Scientific Director of the National Institute of Health (NIH) and Director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Dr. O’Shea gave us an update on the current research being performed by these national institutes to search for treatments and, more importantly, a cure for arthritis.

As it turns out, it was the second President of the United States, John Adams, who originally recognized the need for our government to support biomedical research. Today the NIH is our nation’s official medical research agency, with a mission to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.  NIAMS works specifically to support research into the causes, treatments, and prevention of arthritis and musculoskeletal and skin diseases.

Dr. O’Shea started by giving us some historical context, explaining how the molecular biology revolution of the 1970s culminated in the Human Genome Project, which was completed in 2003. The Human Genome Project let to the discovery of monoclonal antibody technology, which led to the discovery of hundreds of cytokines, a term used for a large and diverse family of molecules that relay signals within our immune systems. One of the purposes of cytokines is to regulate the body’s inflammatory response by communicating with other cells, so understanding how these molecules work is very useful for figuring out how to treat (and eventually cure!) RA and other autoimmune diseases.

In patients with RA, an oversupply of several types of cytokines can end up increasing inflammation and triggering joint damage. Among others, these cytokines include tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6). The identification of these specific cytokines let to the development of biologic response modifiers, or medications we know simply as “biologics.” These medications are made up of genetically engineered proteins, derived from human genes, which work to inhibit the communication of particular cytokines that play pivotal roles in inflammation (for example, you may have heard the terms TNF-blocker or IL-1 inhibitor). There are now at least 25 different targeted therapies that have been approved to treat autoimmune diseases like RA. These biologic medications have completely revolutionized the treatment of arthritis.

The most recent arthritis research at the NIH has been on the topic of janus kinase inhibitors, or JAK inhibitors. While JAK inhibitors work similarly to biologics, by working to inhibit or block communication by particular cytokines, JAK inhibitors have some benefits over biologics. First, while biologics must be administered either by injection or infusion, JAK inhibitors can be taken orally, either once or twice daily. Secondly, while biologics are produced from live organisms, JAK inhibitors do not require as complex of a manufacturing process which means that they are likely to cost significantly less than biologics.

As scientists learn more about the specific ways our immune systems function they are then able to help create more specific treatments. As Dr. O’Shea put it, scientists are working to discover how “switches” within our immune system can be used to treat different conditions. As an example, if you wanted to turn off a light in a room you don’t need to destroy the light bulb – you just need to find the appropriate switch in the room to make the light turn off. Likewise in our bodies identifying which “switches” trigger certain immune responses can help us develop treatments for diseases like RA and other autoimmune diseases.

While these discoveries present significant new treatment options for people living with RA, there are still future research challenges to be faced. Unfortunately, scientists still don’t know why some drugs work for some people with RA but not for others – and we still don’t understand why people get autoimmune diseases in the first place. And while we have every reason to be optimistic about progress over the next 15 years, we still need dedication, commitment, and additional research funding to have any chance of finding a cure.

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