Summary: A new study highlights that skin pigmentation can influence how quickly medications reach their intended targets, with melanin potentially binding to certain drugs and slowing their efficacy. Researchers argue that this overlooked factor in drug testing could lead to varied drug responses across skin tones, impacting drug safety and dosing.
Current FDA guidelines lack provisions addressing pigmentation’s effects on drug interactions, raising concerns for inclusivity in treatment efficacy. By using diverse 3D skin models, the study proposes a way for pharmaceutical companies to test drug interactions across skin types.
The findings urge an inclusive approach in preclinical and clinical trials to ensure medications work effectively across all patient demographics. This shift is supported by recent regulatory changes emphasizing diversity in drug development.
Key Facts:
- Melanin Interaction: Melanin can bind to drugs, affecting drug availability and efficacy across different skin tones.
- FDA Diversity Gaps: Existing FDA guidelines do not fully address skin pigmentation in drug testing.
- Proposed Solutions: Diverse 3D skin models could better assess drug interactions, promoting equitable treatments.
Source: UCR
A pair of scientists report in a perspective article published in the journal Human Genomics that skin pigmentation may act as a “sponge” for some medications, potentially influencing the speed with which active drugs reach their intended targets.
The researchers argue that a sizable proportion of drugs and other compounds can bind to melanin pigments in the skin, leading to differences in how bioavailable and efficacious these drugs and other compounds are in people with varying skin tones.
“Our review paper concludes that melanin, the pigment responsible for skin color, shows a surprising affinity for certain drug compounds,” said Simon Groen, an assistant professor of evolutionary systems biology in the Institute of Integrative Genome Biology at the University of California, Riverside, and a coauthor on the paper.
“Melanin’s implications for drug safety and dosing have been largely overlooked, raising alarming questions about the efficacy of standard dosing since people vary a lot in skin tones.”
According to Groen and coauthor Sophie Zaaijer, a consultant and researcher affiliated with UC Riverside who specializes in diversity, equity, and inclusion (DEI) in preclinical R&D and clinical trials, current FDA guidelines for toxicity testing fail to adequately address the impact of skin pigmentation on drug interactions.
“This oversight is particularly concerning given the push for more diverse clinical trials, as outlined in the agency’s Diversity Action Plan,” Zaaijer said. “But current early-stage drug development practices still primarily focus on drug testing in white populations of Northern European descent.”
In one example, the researchers found evidence of nicotine affinity for skin pigments, potentially affecting smoking habits across people with a variety of skin tones and raising questions about the efficacy of skin-adhered nicotine patches for smoking cessation.
“Are we inadvertently shortchanging smokers with darker skin tones if they turn to these patches in their attempts to quit?” Groen said.
Groen and Zaaijer propose utilizing a new workflow involving human 3D skin models with varying pigmentation levels that could offer pharmaceutical companies an efficient method to assess drug binding properties across different skin types.
“Skin pigmentation should be considered as a factor in safety and dosing estimates,” Zaaijer said. “We stand on the brink of a transformative era in the biomedical industry, where embracing inclusivity is not just an option anymore but a necessity.”
According to the researchers, skin pigmentation is just one example. Genetic variations among minority groups can lead to starkly different drug responses across races and ethnicities, affecting up to 20% of all medications, they said.
“Yet, our molecular understanding of these differences remains very limited,” Zaaijer said.
The researchers acknowledge that transformations enhancing inclusivity — encompassing race, ethnicity, sex, and age — demand a comprehensive overhaul of all FDA guidelines on clinical endpoints to align with the FDA’s Diversity Action Plan.
“It’s a monumental task, requiring clear lines of communication between academics, industry researchers, clinicians, and regulators,” Zaaijer said.
“The future of medicine relies on our capacity to connect these currently isolated operational teams.”
The researchers point out that a shift towards inclusive drug development is set to take place as instigated by a new law, the Food and Drug Omnibus Reform Act, enacted in 2022.
“The FDA published their draft guidelines recently,” Zaaijer said. “Once final in a few months, they will mandate considering patient diversity in clinical trials and preclinical R&D. The next step is to provide guidance on what pharmacokinetic variables should be tested in drug R&D pipelines in their pursuit to equitable drugs.”
The researchers hope to activate the pharmaceutical industry and academia to start doing systematic experimental evaluations in preclinical research in relation to skin pigmentation and drug kinetics.
They also encourage patients, their advocacy groups, and clinical trial participants to ask questions related to ancestry-specific drug efficacy and safety, such as, “Has this drug been tested to see if it’s safe for people from different ancestral backgrounds, including mine?”
Clinicians and pharmaceutical representatives should be able to provide an easy-to-understand document outlining the results of the various tests, the researchers said.
They acknowledge that in the current state of drug development this will be hard.
“In terms of risk profile testing, drugs are most often tested on one or a few human cell models that mostly come from donors of Northern European descent,” Zaaijer said.
“Drugs are then tested in a rodent model. If these tests are successful, drug companies push the drug through to clinical trials.
“But are drugs ready to be given to a diverse patient group if they haven’t first been tested, for example, on human cell models of different ancestries? Would you bungee jump off a bridge if you know the ropes have not been tested for your weight category? Unlikely. So why is this currently acceptable with drugs?”
Groen explained that in different ancestral backgrounds certain genetic variants are more prevalent. Those variants can affect how a drug is metabolized and how it behaves in a body, he said.
“If different ancestral backgrounds are taken into consideration in the early stages of drug discovery, then diverse groups of people may have more trust in the drug development process and enroll in clinical trials because they will be better informed of any potential associated risks,” he said.
About this neuropharmacology research news
Author: Iqbal Pittalwala
Source: UCR
Contact: Iqbal Pittalwala – UCR
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Implementing differentially pigmented skin models for predicting drug response variability across human ancestries” by Simon Groen et al. Human Genomics
Abstract
Implementing differentially pigmented skin models for predicting drug response variability across human ancestries
Persistent racial disparities in health outcomes have catalyzed legislative reforms and heightened scientific focus recently. However, despite the well-documented properties of skin pigments in binding drug compounds, their impact on therapeutic efficacy and adverse drug responses remains insufficiently explored.
This perspective examines the intricate relationships between variation in melanin-based skin pigmentation and pharmacokinetics and -dynamics, highlighting the need for considering diversity in skin pigmentation as a variable to advance the equitability of pharmacological interventions.
The article provides guidelines on the selection of New Approach Methods (NAMs) to foster inclusive study designs in preclinical drug development pipelines, leading to an improved level of translatability to the clinic.
