Leading expert in genetics and precision medicine, Dr. Esteban Burchard, MD, explains how individual genetic ancestry directly influences medication efficacy and safety, citing the stark example that the blood thinner Plavix is ineffective in 65% of people of Asian descent due to a common genetic mutation, and highlights how his research into pediatric asthma aims to predict which treatments will work best for each child based on their unique genetic profile.
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How Genetic Ancestry Influences Medication Response and Treatment Efficacy
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- Precision Medicine Defined
- Plavix Ineffectiveness in Asian Populations
- Pharmaceutical Knowledge and Lawsuit
- Asthma Treatment and Genetic Research
- Goal of Personalized Therapy
- Genetic Testing and The Future
- Full Transcript
Precision Medicine Defined
Precision medicine, also known as 4P medicine, is a modern approach to healthcare that is Predictive, Personalized, Preventive, and Participatory. Dr. Esteban Burchard, MD, a top expert in the field, emphasizes that this model moves away from a one-size-fits-all strategy for treatment. Instead, precision medicine uses a patient's unique genetic makeup to predict their response to medications, personalize their treatment plan, prevent adverse reactions, and actively involve them in their care decisions.
This approach is crucial because pharmaceutical companies often develop and market "blockbuster" drugs intended for millions of people without regard for individual genetic variability. Dr. Anton Titov, MD, discusses this paradigm shift with Dr. Burchard, highlighting how genetics is at the forefront of determining individual medication response and preventing serious side effects.
Plavix Ineffectiveness in Asian Populations
A powerful example of pharmacogenomics—how genes affect a person's response to drugs—is the medication clopidogrel, commonly known as Plavix. Dr. Esteban Burchard, MD, explains that Plavix is a prodrug, meaning it must be activated by a specific liver enzyme, cytochrome P450, to become therapeutic and effectively prevent heart attacks and strokes. A significant genetic mutation affecting this enzyme is present in a large portion of the population.
This mutation is highly prevalent in people of Asian DNA ancestry. Dr. Esteban Burchard, MD, states that approximately 65% of Asians carry this mutation, which renders them unable to convert Plavix into its active form. For these individuals, taking the drug is essentially equivalent to taking a placebo, offering no protective benefit against life-threatening cardiovascular events despite being prescribed it.
Pharmaceutical Knowledge and Lawsuit
Perhaps the most alarming aspect of the Plavix story is that the pharmaceutical manufacturers, Bristol Myers Squibb and Sanofi Aventis, have been aware of this genetic issue for over a decade. Dr. Esteban Burchard, MD, notes that despite this knowledge, they continued to aggressively market the multi-billion dollar drug globally, including to populations where it was known to be ineffective for a majority of patients.
This led to legal action. The Attorney General of Hawaii filed a lawsuit against the companies on behalf of the state's residents, accusing them of "willful deceit" and negligence. The lawsuit alleges the companies knowingly profited from selling a medication that they knew did not work for a large segment of the population they were targeting, a stark example of why genetic considerations must be prioritized over profit.
Asthma Treatment and Genetic Research
Dr. Esteban Burchard, MD's primary research focus is on asthma, particularly in children. He and his team have built the largest and most racially diverse pediatric asthma genetic study in the United States. Their work investigates a critical paradox: the patient populations with the highest prevalence of asthma and the highest death rates from the disease often have the poorest response to standard asthma medications.
Dr. Burchard's research aims to identify the specific genetic variants that predict whether a child will have a good or bad response to common asthma treatments. This application of precision medicine seeks to move beyond broad racial categories and instead focus on individual genetic markers to guide therapy, ensuring that each child receives the medication most likely to help them.
Goal of Personalized Therapy
The ultimate goal of this genetic research, as explained by Dr. Esteban Burchard, MD, is to provide truly personalized medical care. In the future, a doctor could use a simple genetic test to tell a patient, "Because you have this specific genetic mutation, this medication will work well for you, but that one will not." This eliminates the trial-and-error approach that can lead to poor health outcomes and unnecessary suffering.
Dr. Anton Titov, MD, and Dr. Burchard clarify that while race or ethnicity can be a crude proxy for genetic ancestry, what matters most is the genetics at the individual gene level. Precision medicine seeks to make broad racial classifications irrelevant for treatment decisions by focusing on the precise genetic factors that determine drug metabolism and efficacy.
Genetic Testing and The Future
The field is advancing rapidly, with regulatory bodies like the U.S. FDA now often requiring information on genetic ancestry and specific gene-drug interactions to be included in a medication's official package insert. This empowers physicians to make more informed prescribing decisions. The work of experts like Dr. Esteban Burchard, MD, is paving the way for a new standard of care where genetic testing becomes a routine part of the diagnostic process.
This ensures that patients receive a correct and complete diagnosis that includes genetic factors, leading to the best possible personalized treatment strategy. Seeking a medical second opinion can be a valuable step for patients to confirm their diagnosis and ensure their treatment plan incorporates the latest advances in precision medicine for conditions like asthma and cardiovascular disease.
Full Transcript
Plavix is useless in 65% of people with Asian DNA ancestry.
Precision medicine is already here. It is 4P Medicine: Predictive, Personalized, Preventive, and Participatory. Individual genetic DNA ancestry influences response to medications. Take the example of the blood-thinning medication Plavix (clopidogrel). This medication is useless in 65% of Asians because they have a genetic mutation that renders the drug useless.
How genes affect response to medication: examples of individual variability in response to asthma treatment and Plavix (clopidogrel). Hispanic ethnicity can mean poor response to asthma treatment. Precision medicine helps individual patients get the treatment that works best for them. The goal is to develop targeted treatments for each person.
Medical second opinion confirms that an asthma diagnosis is correct and complete. Medical second opinion ensures that genetic DNA ancestry information is included in the diagnosis of asthma. It also helps to choose the best personalized treatment strategy for asthma in children and adults. Seek medical second opinion on asthma and be confident that your precision medicine treatment is the best.
Dr. Anton Titov, MD: How do my genes affect response to medicines? Personalized medicine, precision medicine, medical second opinion, "4P Medicine": Predictive, Personalized, Preventive, and Participatory. This term defines a very ambitious goal in precision medicine. We know that pharmaceutical companies pursue blockbuster medicines. Pharmaceutical companies market medicines to millions of people around the world with no regard for a person's unique genetic makeup.
Dr. Esteban Burchard, MD: You use genetics to determine individual response to medications. This is the forefront of precision medicine. You work to determine serious side effects from medications. You do research on asthma in children. Asthma should not be a fatal disease in modern society. Unfortunately, asthma sometimes still leads to the death of children. Personalized medicine can help treat asthma better.
Dr. Anton Titov, MD: What does your research show about the interaction between genetic and environmental factors? How is individual response to medications determined? How can you predict the probability that a person will experience side effects from any medication?
Dr. Esteban Burchard, MD: We know that different racial groups have different risk profiles for disease. We also know that different racial groups respond to treatment in different ways. We demonstrated that patients with the highest prevalence of asthma have the lowest medication response to asthma medications. Patients with the highest death rates from asthma respond to medications poorly. These medications are used all over the world to treat asthma. Precision medicine can help to improve asthma treatment.
Other scientists studied blockbuster medicines, for example, Plavix or clopidogrel. Plavix is used to treat heart attacks or strokes. Scientists found that you need an enzyme, cytochrome P450, to make an active form of Plavix. This active form of clopidogrel creates therapeutic effects. A special mutation has to be present in the enzyme to convert Plavix into its active form.
65% of Asians do not have this mutation. Therefore, 65% of Asian people cannot convert the inactive prodrug into the active form of Plavix. Only the active form of Plavix has a therapeutic effect. So we are giving a placebo to many Asians. They have heart disease or a stroke. A placebo is a substance without any objective treatment effect.
The interesting part is that pharmaceutical companies that make Plavix (clopidogrel) for the last 10 years know about this problem with Asians. These pharmaceutical companies are Bristol Myers Squibb and Sanofi Aventis. But they continue to market clopidogrel (Plavix) to millions of people around the world because Plavix is very profitable for them. It is a multi-billion dollar medication.
The Attorney General of Hawaii recently filed a lawsuit against these pharmaceutical companies. He sued them on behalf of the people of Hawaii because pharmaceutical companies marketed a medication that does not work. These pharmaceutical companies knew about this fact. They have known it for 10 years. Plavix does not work for 65% of Asians. Therefore, pharmaceutical companies showed "willful deceit" and negligence.
This is an example of how genetic DNA ancestry at a particular gene influences the risk of disease. Plavix genetic DNA ancestry determines poor response to medication. There are hundreds of cases like this. The FDA (Food and Drug Administration of the United States) has included in the medication package insert information about the importance of genetic DNA ancestry for treatment efficacy and side effects.
This information talks about the importance of genetic DNA ancestry on a global level and also on an individual gene level. This is an example of the benefits of precision medicine for each person. We are conducting genetic research on asthma. We have built the largest pediatric asthma genetic clinical trial in the United States. It is also the most racially diverse clinical trial of genetic influences in asthma in the United States and in the world.
We are looking at the extremes in the prevalence and death rates. We are asking the question: Are there genetic variants that predict the response of the child to asthma treatment medication? Which child is going to have a good response to asthma medication? Which child is going to have a bad response to treatment of asthma? This is the application of precision medicine to asthma.
We would like to be able to say, "Dear patient, you have this particular mutation. These medications will work well for you. Those medications will not work well for you." This is the goal of precision medicine. Race or ethnicity should not matter for treatment response. Genetic DNA ancestry matters most at the individual gene level. It matters less in a broad racial group. This is the goal of precision medicine.