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Stanford researcher examines pulmonary hypertension — and its link to methamphetamine

de-jesus-perezMany academics begin their talks with a brief synopsis of their current work. Some prefer to open with an overview of their research field. Still others will introduce their topic with a personal anecdote. Vinicio de Jesus Perez, MD, an assistant professor of medicine at Stanford, begins his presentations by showing clips from Breaking Bad, the television series about a terminally ill high-school chemistry teacher in need of money who turns to making and selling meth.

It may seem like an unusual move, but de Jesus Perez believes it makes an important point about his work with pulmonary arterial hypertension patients.

Pulmonary arterial hypertension – a type of high blood pressure that affects arteries in the lungs and heart – primarily affects young women, presents with right heart failure, and without therapy, leads to death. It’s a rare disease, and the current therapies – vasodilators – are not curative. While there’s a lot that scientists don’t know, including why two-thirds of patients are women, what is understood is the direct relationship between pulmonary hypertension and the use of illicit drugs such as cocaine and methamphetamine.

His patients with meth-induced pulmonary hypertension have provided one direction for de Jesus Perez’s work. As described in a recent article, he used gene sequencing to identify “an interesting gene called carboxylesterase-1, which seems to be involved in the way the body metabolizes and degrades amphetamine-like compounds.” After looking at the gene and its product, de Jesus Perez and colleagues found that “methamphetamine-addicted patients had much less of the protein and demonstrated reduced signaling activity associated with a mutation.” The hope, he said, is that “if we can correct that mutation, endothelial cells in the lung might become resistant to damage from methamphetamine and more driven to regenerate after serious injury.”

But methamphetamine isn't the only cause of this incurable disease: There's also a form of pulmonary hypertension whose origins are unknown; this idiopathic form affects 12 to 13 patients per million per year. De Jesus Perez described his patient population as varying from “a 30-year-old woman after giving birth to her first child to a 40-year-old who rehabilitated herself from methamphetamine to someone with HIV.”

The key to better therapies for this disease is understanding its pathobiology first. De Jesus Perez and his colleagues have started there: “We take genetic data from our patient population to mine to identify possible genes of interest related to the pathobiology of pulmonary hypertension. Next we use both animals and cell systems to piece out the relevance of those genes to disease development. Then we make a map to connect the dots to put those candidate genes in perspective. Then we can speculate as to whether one or more genes associated with that pathway may be a druggable target. Next we implement drug development strategies to see if there are compounds out there that can potentially be used.”

There's no shortage of patients who could benefit from new therapies. “I’ve been taking care of patients who are afflicted with the condition for 16 years,” said de Jesus Perez, who recently received a Young Physician-Scientist Award from the American Society for Clinical Investigation for his work. “This diagnosis is a life changer, and it takes a lot of emotional energy to be able to deal with it.”

Previously: Another piece of the pulmonary-hypertension puzzle gets plugged into placeBasic biochemical puzzles that help diagnose and treat disease and Do the benefits outweigh the risks in targeted hypertension treatment?
Photo courtesy of Vinicio de Jesus Perez

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