Eetu Mustonen / SHUTTERSTOCK.COM
SAN DIEGO—In just two decades, precision medicine has gone from futuristic concept to realistic toolbox for clinical physicians. At the 2017 ACR Clinical Research Conference on Nov. 3, the Precision Medicine in Rheumatic Diseases: Hopes and Challenges lecture featured rheumatologists and experts on genetics, genomics, pharmacogenetics and big data who spoke about the latest research in this field and how it may lead to truly personalized rheumatology.
Different Definitions
Precision medicine is an umbrella term that may mean different things to different people, said Soumya Raychaudhuri, MD, PhD, associate professor of medicine at Harvard Medical School in Boston, and professor of genetics at the University of Manchester in England.
“What is precision medicine? If you go to the NIH [National Institutes of Health] website and look at the Precision Medicine Initiative, it says, ‘Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment and lifestyle for each person.’ But it’s also seen as a medical model customized and tailored to the individual patient,” said Dr. Raychaudhuri, who co-chaired the conference with Lindsey Criswell, MD, MPH, professor of medicine at the University of California, San Francisco.
“My take on it is that precision medicine is very much about technology and data, and integrating [those] data into our model of how we approach patient care. So precision medicine exploits the intersection of clinical information, which we use all the time, and high-resolution individual patient data, to elicit effective treatment decisions,” he said.
Dr. Raychaudhuri
The Human Genome Project, a massive effort to map the entire human genome funded by the NIH and completed in April 2003, was precision medicine’s launching pad, leading to such technologies as human genome sequencing, transcriptional profiling and immune cell profiling using mass cytometry, which allows researchers to examine up to 40 biomarkers per cell, Dr. Raychaudhuri said.1 Researchers can now develop a transcriptome for a single cell and use it to sequence thousands of cells, and can also use new epigenetic technologies to “query the genome to determine the areas that are active at any time, allowing us to quickly identify which promoters and enhancers in the genome are active in this particular patient.”
Practical examples of precision medicine in clinical practice already exist, such as:
- Using pharmacogenetics to tailor drug therapy, such as testing for TMPT enzyme activity or a TMPT genotype before starting azathioprine therapy;
- using genetic sequencing technology to define rare diseases; and
- sero-immunotyping a patient to gather data to inform treatment decisions.
With technology becoming more affordable, faster and accessible, “there are exponential expectations” for precision medicine, Dr. Raychaudhuri said.
Personalized Rheumatology
How can precision medicine help rheumatologists diagnose and treat monogenic, autoinflammatory diseases? One example: When young children from two different states were suffering recurrent strokes, researchers used new gene sequencing techniques to discover recessive, inherited loss-of-function mutations in their CECR1 gene associated with an inflammatory phenotype, including early-onset strokes and vasculitis.2 Eventually, this data led the rheumatologists to treat the children with biologics that halted their strokes, said Daniel Kastner, MD, PhD, Intramural Research Project Director at the National Human Genome Research Institute (NHGRI) of the NIH.
