In the last few decades there has been a lot of progress in the development of rheumatoid arthritis (RA) treatment. Novel medicines, such as TNF-alpha inhibitors, are added to the arsenal of doctors to treat this disease. However no treatment works in every RA patient and trial-and-error is currently the only way to find out how effective each drug is. If a patient doesn’t show a decline in symptoms such as swollen joints and muscle weakness in three or four months, the next drug is tried and so on. Spending a year to find the right medication is a distinct possibility, all the while suffering disease symptoms and possible side effect of the medication. This process is also expensive for society.
“We can look for these subtypes with systems biology,” explains Van Wietmarschen, “by measuring small chemicals in blood and urine of patients. But then we don’t know what we are looking for. We decided that it’s better to start out with some idea: that’s were Chinese diagnostics came in. Chinese doctors evaluate patients in very early stages of disease development, when we Westerners wouldn’t even see these patients in the clinic. Chinese diagnoses are based on subtyping. In the case of RA, those can be determined by a range of symptoms and affiliated with either ‘cold’ or ‘heat’. We have tried to validate these subtypes with Western science, to see whether they could be used as a starting point to determine the optimal treatment for those patients.”
Thirty patients were diagnosed by Traditonal Chinese doctors, after which their blood and urine was analyzed for metabolites and gene expression. Van Wietmarschen: “We found 64 genes that where expressed differently between the groups, mostly related to apoptosis. And we could measure higher levels of acylcarnetines in the urine of the ‘heat’ group patients, which is related to muscle breakdown. As RA is a muscle degenerative disease, this is worth looking into in more detail.”
Following up his PhD research, Van Wietmarschen is collaborating with the Academic Medical Centre Utrecht in an attempt to predict the response of RA patients to drugs, based on their symptom profiles. Patients in this study fill in a symptom questionnaire to determine their subtype, and will be followed during their treatment with a biological drug. Response to the treatment will be evaluated after three months. “The long term goal of these types of research,” Van Wietmarschen tells us, “is to build bridges between Chinese and Western medicine.”