Precision and personalized medicine have revolutionized the field of healthcare by tailoring medical treatments to an individual’s unique genetic makeup and health characteristics. In the biological and biopharmaceutical landscape, significant strides have been made in advancing personalized medicine, with notable breakthroughs in the areas of oncology, genetic screening/testing, obesity, and cardiovascular diseases. In today’s Tulane Digest, we delve into the fascinating worlds of precision and personalized medicine, exploring their current applications and the exciting potential both hold for the future.

Precision Medicine: Unraveling the Science of Individualized Care

Although the term “precision medicine” may be relatively new, the concept has been an integral part of healthcare for years. Consider a blood transfusion—rather than randomly selecting a donor, matching the donor’s blood type with the recipient’s minimizes the risk of complications. This fundamental principle of tailoring treatment to the individual’s needs forms the basis of precision medicine.

In the field of oncology, personalized medicine has opened up new possibilities for targeted therapies. Researchers have made remarkable progress in identifying specific genetic mutations that drive the growth of cancer cells. By analyzing an individual’s genetic profile, healthcare professionals can now prescribe targeted treatments that precisely inhibit these specific mutations, increasing the effectiveness of cancer therapies while minimizing side effects. This approach has shown promising results in various types of cancer, improving patient outcomes, and extending survival rates. One example of this innovative approach is found in the lab of Matt Burow, PhD, and Bridgette Collins-Burow, MD, who have created novel patient-derived xenografts (PDX) that facilitate more rapid and personalized treatments. These PDX models, involving the engraftment of tumors from patients with metastatic triple-negative breast cancer into mice, facilitate comprehensive studies on drug resistance, tumorigenesis, and metastasis in breast cancer subtypes. The lab characterizes and utilizes organoids, patient-derived xenografts, and micro-physiological systems to identify therapeutic targets and investigate drug resistance in cancer systems, with emphasis on ER+ and triple-negative breast cancer.

Genetic screening and testing have also seen notable advancements in the realm of personalized medicine. Rapid advancements in gene sequencing technologies have made it possible to identify genetic predispositions to diseases at an earlier stage. This enables healthcare providers to implement preventive measures or personalized treatment plans to mitigate the risk of developing certain conditions. By understanding an individual’s genetic susceptibility to diseases such as Alzheimer’s, Parkinson’s, or certain types of cardiovascular disorders, healthcare professionals can tailor interventions to manage or delay the onset of these conditions, significantly improving patients’ quality of life. Several universities, including Johns Hopkins University, the University of Pennsylvania, and Tulane University, have prioritized genomic precision medicine research by creating research centers or cohorts with these areas of focus. In fact, researchers at Johns Hopkins have created a Precision Medicine Analytics Platform that provides data sets from various sources (i.e. electronic medical records, radiology imaging, research registries, and others) along with analytical tools that can be used as a discovery platform for projects in drug discovery and personalized medicine. The push into this space from universities mirrors the push from industry, where companies such as Novartis, Pfizer, and AbbVie have included precision medicine as an area of innovation that they are prioritizing.

The Promising Future of Precision and Personalized Medicine

Although this field is relatively young, it will continue to revolutionize the way we approach healthcare. By harnessing the power of genomics, biomarker testing, and individualized care technologies—and synching them with the capabilities of AI and machine learning—we will continue to pave the way for a future where diseases are detected earlier, treatments are tailored to individual needs, and prevention becomes the cornerstone of healthcare. The integration of precision medicine into public health initiatives will empower individuals to take charge of their own well-being and enable an increased understanding of healthcare in addition to more rapid and positive outcomes.

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The Tulane Medicine team, who is also the Tulane Digest Team, is partnering at BIO 2023 this week. You can send a request through the BIO partnering system, or email us directly to arrange a time to connect.

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Curated Research and Research-Related News Summaries, Analyses, and Syntheses. Published on behalf of The Tulane University School of Medicine. Content is generated by reviewing scientific papers and preprints, reputable media articles, and scientific news outlets. We aim to communicate the most current and relevant scientific, clinical, and public health information to the Tulane community – which, in keeping with Tulane’s motto, “Not for Oneself but for One’s Own”, is shared with the entire world.

Kaylynn J. Genemaras, PhD: Editor-in-Chief

Maryl Wright Ponds, MS: Research and Writing Assistance

Special thanks to James Zanewicz, JD, LLM, RTTP, and Elaine Hamm, PhD, for copyediting assistance

In the realm of drug development, animals like rodents and non-human primates have proven instrumental in assessing the safety and efficacy of many potential treatments. However, the increasing availability of innovative technologies—such as organ-on-a-chip, fat-on-a-chip, nerve-on-a-chip, and organoid models—is heralding a shift towards new alternative methods (NAMs) of drug testing. Today’s Tulane Digest delves into the exciting advancements in the field as a whole and highlights some of the transformative contributions by academia and start-ups that are propelling us toward a more efficient future for preclinical drug testing.

The Need for Change and the FDA Modernization Act

The utilization of animals in drug development has historically been driven by a lack of viable alternatives. With the passage of the FDA Modernization Act in December 2022, a paradigm shift has been initiated. As part of the new drug application process, pharmaceutical companies are now required to submit preclinical data on their compounds before proceeding to human clinical trials. Even with the use of extensive animal studies in drug development, translation gaps leading to high attrition rates, toxicological concerns, inconsistent replication of results in humans, and suboptimal efficacy profiles have persisted. This has intensified calls for reform and accelerated the exploration of NAMs for drug testing.

Introducing New Alternative Methods

NAMs encompass a wide range of innovative approaches, including cell-based assays, organ-on-a-chip technologies, computer modeling (including some applications of ), and micro-physiological systems. These cutting-edge methodologies enable researchers to study the impact of compounds or environmental factors on human biological systems, bridging the gap between animal models and the human body. By utilizing NAMs, the understanding of how active ingredients function in a human model is greatly enhanced before progressing to human testing.

Promising Breakthroughs

Organ-on-a-chip and organoid research have made incredible breakthroughs in recent years and can be found in research institutions and start-up companies alike. The India Institute of Science has done prolific work on a heart-on-a-chip model to study cardiovascular diseases. Seoul National University has done extensive work in the realm of kidney-on-a-chip models, highlighting that microfluidic chips can very closely resemble in vivo modeling. Tulane University’s Dr. Ryosuke Sato also focuses on kidney alternatives in the form of kidney organoids. Dr. Sato’s in vitro kidney organoids are cultured and created from stem cells to form a system that mimics the function of human kidneys. Once formed, these kidney organoids can be challenged in drug toxicity experiments to screen for compounds that have the highest chances of safety.

Startups with promising alternative drug testing technologies include Obatala Sciences, Emulate Bio, and AxoSim. Obatala Sciences is led by CEO Trivia Frasier, PhD, MBA, and they have created a breakthrough technology that has immense applications in various organ-on-a-chip models, providing an accurate representation of human organ environments. Obatala Sciences develops and commercializes many organ-on-a-chip models that researchers use for drug testing and therapeutic discovery, such as ObaGel®, the first commercially available human-derived hydrogel. Further, research from Harvard’s Wyss Institute led to the creation of Emulate Bio, a start-up with products that include kidney-chip, lung-chip, and liver-chip technologies among others. Finally, AxoSim—which was founded by Michael Moore, PhD, and Lowry Curly, PhD, of Tulane University—specializes in nerve-on-a-chip technologies that enable the identification of superior drug candidates earlier, with heightened accuracy and efficiency. AxoSim has several state-of-the-art biomimetic platforms, including 3D human-relevant myelination platforms that are used for neuro-pharmaceutical testing. Each of these commercial technologies provides a unique opportunity to evaluate the potentially toxic effects of drug compounds quickly and accurately without the use of animal sacrifice.

Embracing an Efficient Future

By advocating for the use of alternative methods for drug screening and testing, we take a significant stride towards a world that is more efficient in bringing therapeutics to market. These innovative approaches are often not only more cost-effective than animal testing but also expedite the drug development process. The integration of alternative methods in preclinical drug testing signifies remarkable progress, and as research continues in this area, there is hope that the drug development process can move forward with fewer animal sacrifices and more robust data packages.

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The Tulane Medicine team, who is also the Tulane Digest Team, is partnering at BIO 2023 this week. You can send a request through the BIO partnering system, or email us directly to arrange a time to connect.

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Curated Research and Research-Related News Summaries, Analyses, and Syntheses. Published on behalf of The Tulane University School of Medicine. Content is generated by reviewing scientific papers and preprints, reputable media articles, and scientific news outlets. We aim to communicate the most current and relevant scientific, clinical, and public health information to the Tulane community – which, in keeping with Tulane’s motto, “Not for Oneself but for One’s Own”, is shared with the entire world.

Kaylynn J. Genemaras, PhD: Editor-in-Chief

Maryl Wright Ponds, MS: Research and Writing Assistance

Special thanks to James Zanewicz, JD, LLM, RTTP, and Elaine Hamm, PhD, for copyediting assistance

The opioid crisis is a public health emergency that has had a devastating impact on the US, taking the lives of a staggering 80,411 people in 2021 alone. This epidemic has been a tragedy for those who have lost their lives, and researchers and policymakers alike are searching for ways to put an end to this crisis. Various research labs are exploring alternative analgesics to opioids that offer hope for a brighter, safer future. Join us as we delve into the hopeful and necessary developments in this field.

Combating the Opioid Epidemic with Safer Alternatives

Ongoing research into pain management alternatives, non-opioid medications, and addiction treatment approaches are some of the main methods being used to address the opioid crisis. The FDA is included in this push towards safer alternatives, and they released a draft guidance in 2022 to encourage the development of non-addictive alternatives to opioids for managing acute pain. The aim is to reduce opioid exposure and prevent new addictions, and the guidance outlines recommendations for companies developing non-opioid analgesics, addressing aspects such as drug development programs, labeling claims regarding opioid use reduction, and the use of expedited FDA programs to support development. Although public health measures are equally paramount to the reduction of opioid deaths, the search continues for the optimal pain reliever: one that reduces pain but does not induce an addictive or dependent response.

Pioneers in Opioid Alternative Research

Most opioids on the market today—including morphine, oxycodone, and codeine—target the Mu opioid receptor, which is found on the surface of certain cells in the body, including neurons in the central nervous system. The Mu receptor plays a crucial role in mediating the effects of opioid drugs, and when activated by opioid drugs or endogenous opioids, the Mu opioid receptor initiates a cascade of intracellular events that result in various physiological and psychological responses. These responses include pain relief, sedation, euphoria, respiratory depression, and the potential for addiction. Understanding the Mu opioid receptor and its interactions with opioids is important for developing new medications to treat pain effectively while minimizing the risk of adverse effects and addiction. Researchers are actively studying the Mu opioid receptor and its signaling pathways to develop safer and more targeted treatments for pain management.

Academic institutions, including Shandong University, Yantai University, and Tulane University, are working on novel analgesics that target the Mu opioid receptor. Shandong and Yantai Universities are collaborating to create a Mu-receptor agonist that has a favorable toxicity profile for a novel analgesic. Tulane University’s James Zadina, PhD, in collaboration with the University of Arizona, is also developing an opioid alternative analgesic. Zadina’s breakthrough revolves around a novel opioid alternative pain medication derived from a cyclic peptide that specifically targets the Mu receptor, and this innovative analgesic demonstrates remarkable effectiveness against a wide spectrum of pain, including acute, neuropathic, inflammatory, postoperative, and visceral pain. In fact, its efficacy surpasses that of morphine in certain rodent models, presenting a promising solution for pain management. Unlike its counterparts, this alternative does not possess the same addictive potential, offering hope for individuals suffering from chronic pain, recent injuries, or those undergoing surgical procedures. By minimizing the risk of addiction, this groundbreaking development ensures that patients can receive effective pain relief without compromising their long-term well-being.

Other esteemed universities are actively engaged in exploring different innovative strategies such as utilizing other market drugs and discovering new compounds to address opioid use disorder and improve pain management. Geneva University Hospitals conducted a study where palliative care adults were given intranasal dexmedetomidine—a drug used for sedation—for pain relief, finding this drug to be a feasible alternative to opioids for long-term nursing care. The University of Arkansas is taking a different approach by looking at therapeutic compounds for opioid use disorder, and the University of Warwick is approaching pain medication by creating a compound that targets a specific G-protein receptor. Studying different pharmaceutical targets for pain relief opens the door for innovative solutions that will hopefully one day provide an end to this crisis.

As of October 2022, pharmaceutical companies have 16 new pain medications in Phase III trials with indications ranging from post-operative pain to chronic pain. One such example from this long list of new pain medications is Vertex Pharmaceutical’s compound which was created from research on sodium channels located on pain-sensing neurons. The implications of each of these advancements extend far beyond a single solution: they hold the potential to revolutionize the way people approach pain treatment, benefiting countless individuals worldwide.

Looking Ahead: The Promise of Opioid Alternatives

The opioid epidemic has had far-reaching consequences, devastating lives and straining vital public resources. However, through visionary research conducted at many academic, pharmaceutical, and governmental institutions, a brighter path has emerged. Opioid alternative drugs hold immense potential in reshaping the landscape of pain management, offering effective analgesia while minimizing the detrimental side effects and addiction risks associated with traditional opioids. With collaborative efforts from various high-level universities and a big push from government institutions such as the FDA and the Department of Veterans Affairs, a future where patients can find solace from pain without compromising their well-being is hopefully within reach. As the world embraces these exciting developments, we stand poised on the cusp of a transformative era in pain medicine—a future where compassion, innovation, and improved patient outcomes can converge.

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The Tulane Medicine team, who is also the Tulane Digest Team, is partnering at BIO 2023 this week. You can send a request through the BIO partnering system, or email us directly to arrange a time to connect.

____________________________________________________

Curated Research and Research-Related News Summaries, Analyses, and Syntheses. Published on behalf of The Tulane University School of Medicine. Content is generated by reviewing scientific papers and preprints, reputable media articles, and scientific news outlets. We aim to communicate the most current and relevant scientific, clinical, and public health information to the Tulane community – which, in keeping with Tulane’s motto, “Not for Oneself but for One’s Own”, is shared with the entire world.

Kaylynn J. Genemaras, PhD: Editor-in-Chief

Maryl Wright Ponds, MS: Research and Writing Assistance

Special thanks to James Zanewicz, JD, LLM, RTTP, and Elaine Hamm, PhD, for copyediting assistance

For too long, female biology has been significantly underrepresented in basic and clinical scientific research. From animal studies that only include male subjects to clinical trials that lack women, female biology has been historically understudied. This knowledge gap has had far-reaching implications, leading to a lack of tailored healthcare solutions and an incomplete understanding of female biology.

But, thankfully, times are changing.

A new era of sex-based biology research is emerging, shedding light on the unique needs and complexities of women’s health. This research has the potential to revolutionize healthcare, leading to safer and more effective treatments and preventive measures for everyone.

Sex vs Gender

It must be noted that in this digest and in the realm of scientific research, sex and gender are distinctly different subjects. Gender refers to characteristics that are socially constructed. Sex-based biology focuses on the sex assigned at birth, which has distinct implications, spanning hormonal profiles, drug metabolism, cardiovascular events, lifespan, and even immune system responses to COVID-19.

A Bit of Policy History

Due to the historic omission of female subjects in biological research, the FDA released guidance on the Study and Evaluation of Gender Differences in the Clinical Evaluation of Drugs in 1993. This guidance recommended that drug discovery programs include pharmacokinetic screening as a tool to detect differences and analysis of safety and efficacy by sex. The NIH followed suit with their 2001 mandate created “to ensure the inclusion of women and members of racial and ethnic minority groups in all NIH-funded clinical research in a manner that is appropriate to the scientific question under study.” Further, in 2016, the NIH released their policy known as Sex as a Biological Variable (SABV), which requires researchers to include “sex” as a variable in their studies. Each of these policies has paved the way for more inclusive research.

Sex-Based Biological Research

Studying sex differences in biology includes studying an important hormone: estrogen. Estrogen, a hormone traditionally associated with the female reproductive system, is now being recognized for its broader influence on both males and females. Through rigorous investigation, estrogen is now believed to have protective effects in conditions such as hypertension, osteoporosis, and Alzheimer’s Dementia. Tulane researchers Heddwen Brooks, PhD, Jill Daniel, PhD, and Franck Mauvais-Jarvis, MD, PhD—who are key members of Tulane’s Center of Excellence in Sex-Based Biology—are working to understand the mechanisms behind the protective effects estrogen has on metabolic homeostasis, cardiometabolic health, inflammation, hypertension, and other diseases/conditions. One prominent example of the importance of studying estrogen effects is seen in post-menopausal women, who suffer from high blood pressure, asthma, and cardiovascular events at much higher rates than menopausal and pre-menopausal women. This difference is likely due to the drop in estrogen that occurs after menopause, and insights from these studies could lead to better therapeutic targets and better hospital care for both women and men, as estrogen is not exclusive to women.

Another area of interest in sex-based research is clinical pharmacology, as various studies have shown that men and women metabolize compounds differently. In fact, women are 50-75% more likely than men to experience an adverse drug reaction, likely due to differences in drug bioavailability and pharmacokinetics. In her study, Sex Differences in Pharmacokinetics and Pharmacodynamics, Offie Soldin, PhD, MBA, discussed how and why women and men have different responses to drugs. Soldin’s research was part of another university center studying sex differences—Georgetown University’s Center for the Study of Sex Differences in Health, Aging & Disease. The establishment of these types of research centers is an example of the paradigm shift currently happening, where research on biological sex differences is gaining the focus and attention it deserves.

Charting the Future of Sex-Based Biology Research

The remarkable biological differences that exist between men and women are just beginning to be understood, and researchers currently have a much better understanding of the importance of sex-based biological studies. Although we have a long way to go, we find ourselves at the dawn of a new era—a time when female representation in biological research is increasing and the knowledge gap between men’s and women’s health can begin to close. With an increased understanding of sex differences in biological research comes increased healthcare options for both men and women. Further, since mothers make approximately 80% of healthcare decisions for their children, it makes both scientific and economic sense to use the research on sex differences to promote and prioritize women’s health equity to ensure the entire population has access to safe and effective treatments.

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BIO 2023

The Tulane Medicine team, who is also the Tulane Digest Team, is partnering at BIO 2023 this week. You can send a request through the BIO partnering system, or email us directly to arrange a time to connect.

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