Unlocking the mysteries of autoimmune disease

Dr Ben Porter-Brown, Clinical Director of Development, practiced internal medicine and rheumatology prior to joining Roche. For the last 10 years he has been working in arthritis and autoimmune research.

Dr Ben Porter-Brown, Clinical Director of Development

Research and development is not unlike attempting to solve a good mystery: look for prime suspects, investigate weak alibis, and disentangle story lines. Once the perpetrator is confirmed, in hindsight the clues all fall into place.

Rheumatologists treat a range of autoimmune and inflammatory diseases, many of which remain a medical mystery to a large extent. In rheumatoid arthritis (RA), we do not know what the body is mounting itself against. It still proves difficult to tease out the main underlying drivers. And the history of how RA has been treated bears that out. One of the first approaches levied therapies from other diseases as a rudimentary way to address the signs and symptoms of RA. Today, we know much more about what is going on inside a person’s immune system and are able to specifically target certain pathways to slow down or mitigate RA. Each new therapeutic target that was identified helped us to assess the underlying immunopathogenesis of the disease. Our understanding of the different pathways in autoimmune inflammation has evolved. And that has opened a new window into how we think about, and potentially solve, the mystery of other autoimmune diseases.

Why does that become interesting?

Despite major advancements in the past 15-20 years, there are still autoimmune conditions without optimal solutions meaning that patients are suffering. Giant cell arteritis (GCA) is a rare condition that causes severe inflammation of blood vessels, often around the temple.  GCA can cause headaches, jaw pain, fever and fatigue. One in five people with GCA experience vision problems, in some cases leading to blindness. Unfortunately, in GCA we are short-handed in tailored treatment options with potential quality of life issues linked to the current standard of care therapies.

Systemic sclerosis (SSc) causes thickening of the skin leading to disfigurement of areas of the body such as face and hands. SSc can also impact internal organs and in some cases, cause fatal damage to the heart, lungs, stomach or kidneys. People with SSc face significant challenges in their day-to-day living - all the things we take for granted feel insurmountable, buttoning clothes is laborious and often not possible. Poor outcomes in SSc can be attributed to the fact that there has yet to be a specific treatment addressing the underlying cause of the disease.

Known unknowns

Some autoimmune diseases share underlying pathophysiology and there is evidence that some synergies may provide new treatment opportunities.  But researchers need to find out more. The pattern we see repeatedly in RA is irrespective of target, there is a ceiling of response. How do we overcome that?

As we investigate new therapeutic approaches, we must be ever mindful of the trade-off between suppressing activity and leaving immune response intact for other purposes. You can only hit the system so hard before it breaks. New autoimmune targets will feature prominently in overcoming this challenge as will our ability to better characterise key inflammatory pathways, but the sequence in which we use available therapies will also be important.

The characteristic heterogeneous nature across the spectrum of autoimmune disease gives cause to challenge preconceived ideas about pathology and to try to better segment these populations.  Our best shot at unlocking this mystery is to take a collaborative approach across academia and industry. I hope that in my lifetime we are able to solve the mystery of many of these autoimmune disease, and improve the millions lives affected by these collection of conditions.