Personalized medicine helps the patient to exploit useful genetic information

Dr Richard Altman reviewed the chart of his patient, David Clay, as well as his personal experience as Clay’s primary care physician at UCHealth Lone Tree Medical Center. Over the past few months, Clay had experienced more nighttime anxiety. Altman reviewed the dose of citalopram (Celexa) he had previously prescribed and decided there was room to increase it.

As Altman was typing the command, a message appeared in UCHealth’s electronic health record. The post informed Altman that Clay has a version of a gene called CYP2C19. This polymorphism – in automotive terms, same model, but with an automatic transmission versus a shifter – meant that Clay’s liver was probably metabolizing citalopram much faster than an average patient. This, in turn, meant that he would need an above-average dose for the drug to have its normal effect. Altman was going to increase the dose anyway, but the pop-up window crystallized for doctor and patient why prescribing a higher dose made sense.

A technician prepares a sample for genetic sequencing at the Colorado Center for Personalized Medicine biobank. UCHealth has collected 85,000 biospecimens since the biobank began collecting biospecimens in 2016. Photo courtesy of JPAC.

Personalized medicine

This was a single alert, linked to a single patient, in a single UCHealth clinic room one day in April 2020. It was also a rapid return on a major long-term investment from UCHealth and the University of Colorado School of Medicine aimed at harnessing genetics to develop new treatments and improve daily patient care.

This investment, announced in 2014, created what is today the Colorado Center for Personalized Medicine (CCPM) and its crown jewel biobank that holds 85,000 biospecimens and counts.

To help someone

Every UCHealth patient has the opportunity to contribute through My Health Connection, and many have done so already. So far, 185,000 UCHealth patients have agreed to contribute to the biobank. The 100,000 patient discrepancy between consents and donors exists because the biobank samples are collected as part of an in-clinic blood draw that the patient needs anyway. But some never do a blood test in the clinic – ophthalmic patients, for example. With others, these blood tests are rare. JPAC is stepping up a campaign to collect saliva (an alternative source of genetic material) to fill this gap.

Clay was among those who signed up, and a few years ago a routine blood test resulted in another sample for the Biobank’s ultra-cold freezers.

Dr Richard Altman
Dr Richard Altman

“I think the doc just asked if I would, because at some point it might help someone,” he recalls.

The big idea behind personalized medicine is to provide artificial intelligence with a buffet of genetic information from a large number of patients, have AI discover the links between genes and diseases, and then d ” use this information to develop therapies suitable for people with particular genetic characteristics. This work is in progress and it will take time.

In the meantime, CCPM is focusing on pharmacogenetics, which has to do with how our genes influence how we metabolize drugs. CCPM started with CYP2C19.

“Huge factor”

You would think that a gene that encodes a liver enzyme responsible for breaking down about 10% of all human pharmaceuticals would have earned a more convincing name than CYP2C19, but so it is. Among the drugs it metabolizes are proton pump inhibitors for stomach ulcers, antidepressants, anticonvulsants, sleeping pills, antimalarials, and drugs that inhibit viral replication. A different version of the gene can slow down or speed up metabolism.

In Clay’s case, he consented and provided a biological sample. This specimen was analyzed by a million dollar Illumina gene sequencer. Citalopram was one of 10 drugs influenced by CYP2C19 that CCPM selected as initial targets for its feedback loop to patients. JPAC worked with the UCHealth Epic team to create an alert that appears just at the right time so as not to distract or even annoy physicians who have faced an increasing number of alerts with the transition to medical records. electronic health. These alerts then arose for patients with polymorphisms that either accelerated the drug’s breakdown (as in Clay’s case) or slowed it down (meaning that a standard dose would become a larger dose than expected).

These alerts did not occur often: 69 times in the past 18 months or so. But it’s a start, and Altman, for his part, thinks it’s a positive sign for the future of medicine. “Precision medicine pharmacogenetics” may sound like buzzword, but it can help answer pressing questions in the exam room, says Altman.

“Why is my patient not responding to treatment? Or, “Why does my patient have such a severe reaction when I give them a small dose?” Altman said. “It’s about getting a glimpse of a huge new factor influencing care, such as gender, age or smoking status.

In Clay’s case, this pop-up provided some peace of mind as to why the higher dose was needed. The drug was not failing; he was just processing it faster than most. And drug doses matter, Altman says, whether it’s improving cholesterol, lowering blood pressure, or improving mood.

“From the doctor’s point of view, you want to give the right dose – no more, no less – to get what the patient needs,” he said.

On the bridge

CCPM does not stop at CYP2C19. The next step in his pharmacogenetics initiative is a gene called SLCO1B1. Certain polymorphisms of this gene can cause muscle pain or worse in patients on certain statins – somewhere between 7% and 29% of them may experience what are known as Statin Associated Muscle Symptoms (SAMS). A statin-related electronic health record pop-up could save patients a lot of pain.

The Center is also looking to add variations of the DPYD gene to its feedback loop. Some flavors of this gene can slow down the breakdown of common chemotherapy drugs, leading to a higher risk of toxicity in cancer patients in treatment. These and other investigations will soon benefit from a new generation of microarray chips that will increase sequencing throughput by a factor of seven.

The most important throughput for the biobank, however, is from UCHealth patients who agree to contribute to the advancement of medical science. Many patients wish to contribute to science in order to contribute to the collective good and to show their appreciation for the care they have received.

Some benefit, of course – David Clay among them.

“In my case, I did it because it might help someone – and it came back and helped me,” he said.

To learn more or to register for the Colorado Center for Personalized Medicine Biobank, visit

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