Stories-Muckle-Wells and Beyond

Muckle-Wells Syndrome is an autoimmune disease resulting in daily fevers, rash, conjunctivitis, swollen joints and hearing loss. It can also lead to several potentially fatal complications. You probably haven’t heard of the disease because not many people get it – maybe only a few hundred in the U.S. and about 10,000 people worldwide. But the disease was known to NIBR physician-scientists, who recognized its pathology and suggested that it just might have some similarities to a much more common ailment suffered by over 3 million men in the US – gout.

Physician-scientists at Novartis reasoned that a rare disease like Muckle-Wells could be a proving ground for an arthritis drug. Both conditions exhibit high levels of an immune system molecule called interleukin-1 beta, which is normally used to fight infection by causing inflammation, allowing more immune cells and antibodies to perfuse into the affected area. But in both diseases the immune system goes haywire, producing an overabundance of interleukin-1 beta and other inflammatory agents, causing the destruction of tissue.

Addressing patient need

In collaboration with a US-based biotech company, NIBR scientists developed a monoclonal antibody drug named ACZ885, which specifically targets interleukin-1 beta, soaking it up like a sponge to limit further damage to surrounding tissues. As a next step, a small “proof-of-concept” study was designed to use ACZ885 to treat Muckle-Wells patients who had a potentially fatal complication called amyloidosis, where protein deposits accumulate in vital organs leading to kidney failure.

When the patients were injected with ACZ885, the results were remarkable. Within hours several patients improved dramatically. Rashes disappeared, fever and pain were reduced. Many patients responded instantly to the injection with an effect whose duration lasted months. This was an amazing turnaround for patients who are often sick every day of their lives.

Targeting rare diseases as a portal to the treatment of more common conditions

Pursuing a therapy for Muckle-Wells Syndrome is something that most pharmaceutical companies would not choose to do, since they are usually inclined to look for drugs that serve large markets. At NIBR, we recognize that many diseases share fundamental molecular pathways, and that even the rarest condition could have important implications for more common diseases. By treating Muckle-Wells, we can serve patients who are in desperate need of options, while gaining a foothold in the search for new treatments for similar diseases, such as gout.

Novartis is not alone in its focus on genetics and molecular pathways for finding new drugs, but it has been at the forefront of a new approach that targets rare diseases as a portal to the treatment of more common conditions.