Note: In the context of this edition of the Tulane Digest and biomedical research, there is an operational distinction between the terms of “sex” and “gender.” “Gender” refers to socially constructed roles, behaviors, expression, and identity. “Sex-based” biology and medicine focus on sex assigned at birth through anatomical, chromosomal or other features. While the interaction between sex, gender, and other identity factors and their impact on health over the course of human life is complex topic requiring dedicated research in the pursuit of health equity, we maintain the narrow definition of biological sex for the scope of this article.

Slipping through the cracks: A continued lack of women in biomedical research

Female biology has long been underrepresented or downright ignored in both basic and clinical biomedical research, with researchers citing reasons such as increased variability in female biological and behavioral responses due to hormonal changes—since disproven in various studies including a meta-analysis of over 300 neuroscience articles—and claims that drugs in early development might harm fertility, despite estimates that the total number of pregnant individuals taking either prescribed or over-the-counter (and often necessary) medications is well over 50%. Though the FDA and NIH have in the past few decades released guidelines and mandates for inclusion of females in clinical trials and basic research, women are still routinely underrepresented in early-stage clinical trials. Even though female non-human animals are now often included in preclinical biomedical experiments, many of these are not followed-up with a proper statistical analysis, nearly negating the reason for their inclusion in the first place.

As a result of these persistent integration failures, women continue to find themselves navigating a healthcare system that does not fully understand their biology, despite observed differences in cardiovascular diseases, Alzheimer’s prevalence, schizophrenia, drug pharmacokinetics; even baseline metrics commonly taken for granted such as normal blood pressure range have recently been observed to differ in women. Furthermore, the hormonal changes of menopause have been shown to alter areas from cardiovascular health to cognition for reasons that are separate from changes purely due to age. At the same time, menopause appears to accelerate cellular aging.  These findings produce further complications for ongoing clinical studies of women’s health over the course of their lifespans. Still, a greater effort to include women in clinical trials has the potential to produce more efficient studies and greater likelihood of long-term drug success. An FDA report found that eight of the ten drugs withdrawn from market between 1997 and 2000 (in some cases, within only a few years of approval) showed higher risk to women. A more rigorous analysis of adverse events and consideration of potential sex-based prescription frequencies could have ended trials earlier in the pipeline, saving considerable expenditure. Some studies find that women are more likely to complete clinical trials, leading to superior retention, greater statistical power, and the potential for shorter time to trial completion.

Even with proper inclusion and analysis, the complexity of interacting sex-related variables and their changes over time have the potential to cause difficulty when crafting accurate and effective research and healthcare strategies to address the unique needs of women. However, institutions are taking heed. The NIH’s All of Us program aims to capture health differences and disparities across the whole spectrum of diverse individuals across the US, and is committed to advancing women’s health research. Tulane University’s Center of Biomedical Research Excellence in Sex-based Precision Medicine is dedicated to conducting projects at the intersection of sex, gender and other genetic, biological, and social factors of health. At Mayo Clinic, the Women’s Health Research Center focuses on advancing sex-based studies and training early researchers in intersectional women’s health research through its BIRCWH program, one of 19 across the nation.

Artificial intelligence as a path to greater fairness in healthcare

In addition to dedicated research, addressing these complex issues requires innovative solutions, and recent advances in artificial intelligence (AI) may help to provide answers. The continued development of AI and machine learning—which have already made great strides in medicine, from evaluating chest X-rays to designing a drug for idiopathic pulmonary fibrosis that reached clinical trials—gives promise for better, less-biased detection of sex-based differences in biology. When trained on vast amounts of appropriate data, AI models are able to detect patterns and relationships in large, complex datasets that might otherwise be invisible to humans. Such models can detect genetic disorders through subtle differences in facial structure or determine how an individual’s cancer evolved, potentially allowing prediction of disease progression.

Within the realm of sex-based biology, artificial intelligence has already shown success. A study using AI found sex-based differences in posture, with potential to guide screening and treatment in physical therapy and sports medicine. Another recent study led by researchers at NYU Langone Health found sex differences in white matter of the brain at the microstructural level, potentially providing insight into why psychiatric and neurological disorders sometimes present differently between men and women. Researchers at the Karolinska Institute in Sweden used AI to find sex-specific gene expression patterns related to calcification of the aortic valve of the heart during aortic stenosis, offering a path toward precision therapies. Within the clinic, properly-trained AI-powered technologies such as ambient clinical documentation or large language model-assisted diagnostics could increase sex health equity by ensuring that symptoms are documented and properly considered, given that women’s health concerns are unfortunately more frequently dismissed by doctors compared with those of men. 

Those who forget the past: Avoiding AI’s potential pitfalls

Despite great promise, it must also be stated that care must be taken when employing such models.  Otherwise, they have the capacity to continue to perpetuate (and even amplify) historical biases against women and other underrepresented groups. An AI model trained on datasets that do not properly incorporate sex as a biological variable may do more harm than good. A recent study examined whether OpenAI’s GPT-4 encoded racial and sex biases in areas such as diagnostic reasoning and clinical plan generation, and found that it did not appropriately account for demographic diversity and tended to overrepresent stereotypes of diseases based on race and sex. If a model is trained on medical texts and diagnoses that were often based on decades of data ignoring sex as a biological variable, it will make many of the same mistakes of the humans who produced that data. But once this is recognized, and after applying more careful algorithm design and a commitment to undoing previous discrimination in medicine, AI systems hold great potential for parsing out sex differences (as well as a plethora of other critical factors impacting health) and ushering in greater health equity for women.

The beginnings of a new era in health equity

Because the dangers are being recognized, discussed and beginning to be addressed, we now have room for cautious optimism. Technological advancements combined with greater awareness of sex-based health inequity at both the level of individual researchers and the US government are adding velocity to a momentum that has been building over the past decades. Through greater outreach to women for inclusion in clinical trials, more careful inclusion of sex as a biological variable in basic research (and appreciation of its value even when a study does not explicit aim to research sex differences), and a commitment to better health care policies and access for women, we have more power than ever before to bring about change and ensure a more equitable future.

____________________________________________________

The Tulane Medicine team, who is also the Tulane Digest Team, is partnering at BIO 2024this week. You can send a request through the BIO partnering system, or email us directly to arrange a time to connect.

____________________________________________________

Recent Podcast Episode Drops:

Whether for travel entertainment or a quick listen between meetings, check out 6 recently released bite-size episodes of BIO from the BAYOU. Check them out on the BftB Website, Apple Podcasts, Spotify, or anywhere you podcast.

____________________________________________________ 

Share the Science: Please forward this issue and encourage others to sign up for Tulane School of Medicine’s Digest Mailing List.

____________________________________________________ 

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.

Alexis L. Ducote, PhD: Editor-in-Chief

Special thanks to James Zanewicz, JD, LLM, RTTP and Elaine Hamm, PhD for copy-editing assistance.

Antibiotics: In Search of the Next Wonder Drug

In a world full of discussions around AI, gene therapy and robotic surgery, antibiotics may seem like relics of early medicine, but their pivotal role in modern healthcare cannot be overstated. In 1900, pneumonia, tuberculosis, enteritis, and diphtheria caused a third of all deaths, especially among children under 5. Early 20^th century advancements in infection prevention such as surgical asepsis and water chlorination improved public health, but treatments were still limited. Existing “cures” like salvarsan and malariotherapy often had severe side effects and were only effective against a limited array of pathogens. This changed in 1928 with Alexander Fleming’s discovery of penicillin leading to the “golden age of antibiotic discovery” from around 1940 to 1960, during which numerous new antibiotics were developed.

The Snake that Ate Its Own Tail: Antibiotic Overuse Creates Resistance

As the field of antimicrobials was evolving, so were the bacteria, spurring an arms race between medical science and microbial adaptation in the form of antimicrobial resistance (AMR). Through genetic mutations and the exchange of resistance genes, bacteria can develop mechanisms to evade the effects of antibiotics and render existing treatments less effective. As an example, many antibiotics – including penicillin and its derivatives – exhibit a chemical structure characterized by a beta-lactam ring (in red).

This is important, as this structure reacts with components of the bacterial cell wall to, quite simply, destroy it. In response to widespread use of beta-lactam antibiotics, bacteria have developed enzymes called beta-lactamases, which cut open the ring before the antibiotic can exert its effect. Bacteria may also utilize efflux pumps to simply remove the drug from the cell before it kills them. As one class of antibiotic loses efficacy and another is brought in to take its place, pathogens may develop multidrug resistance. The World Health Organization (WHO) has identified antibiotic resistance as one of the biggest threats to global health today, with the potential to negate many of the gains of modern medicine over the past century.

Make New Friends, but Keep the Old: Innovative Strategies against AMR

In response to this threat, researchers are employing several innovative strategies to combat antimicrobial resistance (AMR). One approach involves the development of combination drug regimens to directly fight existing resistance mechanisms. One such method—currently being developed by groups such as the US company VenatoRx and researchers at the University of Tunis El Manar—is the use of beta-lactamase inhibitors to specifically target and disrupt the bacterial enzymes which provide resistance against existing antibiotics. Another tactic is phage therapy, which uses bacteriophages to infect and kill bacteria. The Biomedical Advanced Research and Development Authority (BARDA) recently awarded $23.9 million to US company Locus Biosciences, Inc. to continue development of a phage therapy against urinary tract infections caused by drug-resistant E. coli. Meanwhile, Tulane University’s Wimley Lab is developing potent antimicrobial peptides as alternatives to traditional antibiotics. These peptides attack bacterial membranes without requiring specific binding structures, making development of resistance much more difficult. Furthermore, different therapies are contemplated being used in combinations that will hit pathogens through multiple mechanisms, greatly decreasing the chance of their survival and pushing back any ability to development longer-term resistance.

Economic Challenges in Antibiotic Development

Despite significant progress in development of new antimicrobial treatments, bringing a therapy through trials and to patients faces significant challenges due to economic and systemic hurdles. The antibiotic business model is considered broken, primarily because the costs of development are not matched by the financial returns. Governments and organizations are beginning to recognize the gravity of antimicrobial resistance, which could cause 10 million deaths annually by 2050, and are exploring alternative funding models and incentives to stimulate antibiotic research and development. Despite initiatives like GARDP and CARB-X, which aim to accelerate the development of new antibiotics, the current efforts have been deemed insufficient by experts and the World Health Organization. Most new drugs are simply derivatives of existing classes.  This means they arrive on the scene with limited efficacy against resistant strains, and so the global antibiotic pipeline remains underfilled of truly novel and effective solutions. The economic reality is stark: it costs up to $1.5 billion to develop a new antibiotic, but the median sales in the U.S. are only about $16.2 million. This discrepancy highlights the need for a restructured economic approach that not only fosters innovation but also makes the antibiotic market viable and attractive for pharmaceutical companies. A new initiative laid out in the UK hopes to tackle this by introduction of a subscription model and 5-year plan to fund the development of new antimicrobials while slowing further development of resistance. This model would pay pharmaceutical companies a fixed annual fee based on the value of the antimicrobials to the NHS, rather than the volume sold, reducing the incentive for overuse. Meanwhile, in 2023, a group of U.S. Senators and Representatives from both parties reintroduced the Pioneering Antimicrobial Subscriptions to End Upsurging Resistance (PASTEUR) Act in order to drive development of novel antimicrobials and antibiotics.  However, enough bipartisan agreement has not been fully reached for the act to pass and become mandate.

Fostering Global Cooperation to Combat AMR

Overall, stopping the spread of AMR will require a coordinated global effort between governments, clinicians and the biotech industry. Some of the key strategies include the 1) implementation of robust antimicrobial stewardship programs to ensure the rational use of antibiotics and 2) development of truly novel antimicrobials and rapid diagnostics. The One Health approach, aimed at addressing the interconnectedness of human, animal, and environmental health, will be crucial for managing AMR by reducing inappropriate antimicrobial use across all sectors and improving areas adjacent to treatment itself such as hygiene, infection control, and waste management. The development of enhanced surveillance systems is necessary to begin to monitor antibiotic use and resistance patterns, as this information will inform both public policy decisions and regulatory actions. Additionally, accessible public education and awareness campaigns will be help promote a more responsible antibiotic use and prevent infections. A concerted effort from governments, healthcare providers, researchers, and other stakeholders is critical to mitigate the global health crisis posed by AMR and to prevent a return to a pre-antibiotic era that is now dominated not by more mundane infections, but by true super-bugs capable of causing a wave of global pandemics.

 ____________________________________________________

The Tulane Medicine team, who is also the Tulane Digest Team, is partnering at BIO 2024 this week. You can send a request through the BIO partnering system, or email us directly to arrange a time to connect.

____________________________________________________

Recent Podcast Episode Drops:

Whether for travel entertainment or a quick listen between meetings, check out 6 recently released bite-size episodes of BIO from the BAYOU. Check them out on the BftB Website, Apple Podcasts, Spotify, or anywhere you podcast.

____________________________________________________ 

Share the Science: Please forward this issue and encourage others to sign up for Tulane School of Medicine’s Digest Mailing List.

____________________________________________________ 

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.

Alexis L. Ducote, PhD: Editor-in-Chief

Special thanks to James Zanewicz, JD, LLM, RTTP and Elaine Hamm, PhD for copy-editing assistance.

Imagine a world where clinical trials could operate with speed, efficiency, precision, and personalized approaches. This transformative vision is becoming a reality as AI integrates into the clinical trial landscape, offering solutions to long-standing challenges and paving the way for groundbreaking advancements in medical research. By harnessing the capabilities of machine learning, big data analytics, and predictive modeling, AI is optimizing trial processes and enhancing the overall quality and speed of drug development​​.

The traditional clinical trial process is labor-intensive, expensive, and often slow, with an average duration of several years and costs soaring into the millions. One of the critical pain points in clinical trials is patient recruitment and retention. According to the University of Mississippi Medical Center, nearly 80% of all clinical trial sites in the US fail to meet their enrollment targets, leading to significant delays and escalated costs. Additionally, data analysis within trials is mostly manual and error-prone, with researchers grappling to process and interpret vast amounts of complex data. These inefficiencies are exacerbated by rigid trial designs that do not account for patient variability, resulting in suboptimal treatment protocols and frequent amendments that further extend timelines, inflate budgets, and result in failed outcomes.

AI in Healthcare: The Ultimate Patient Whisperer

One of the primary applications of AI in clinical trials is patient recruitment. AI algorithms can analyze large datasets, including electronic health records (EHRs), genetic information, and clinical notes, to identify suitable trial candidates. Companies like Deep 6 AI are revolutionizing this space with platforms utilizing natural language processing and machine learning to rapidly scan millions of patient records. This approach can match potential participants with desired criteria in a fraction of the time required by traditional methods, ensuring that trials can recruit a diverse and representative patient population. Researchers at Cincinnati Children’s Hospital Medical Center also developed a natural language processing and machine learning-based system, the Automated Clinical Trial Eligibility Screener (ACTES), to analyze structured and unstructured data in an Emergency Department setting. The tool successfully reduced patient screening time for clinical research coordinators by 34% and increased overall enrollment rates by 11.1%. By automating time-consuming and high-cost components of the recruitment process, AI accelerates trial initiation and enhances the likelihood of finding eligible participants who meet specific trial requirements.

Retaining participants throughout the duration of a clinical trial is equally challenging. AI can significantly enhance patient engagement and adherence through continuous monitoring using wearable devices and mobile health applications. These tools collect real-time data on patient behavior, symptoms, and medication adherence, allowing researchers to identify and address issues proactively. Several innovative examples of combining wearable devices and AI to enhance trial engagement have been demonstrated in Tulane’s Research Innovation for Arrhythmia Discovery Center. In the iPredict, Prevent study, researchers are working to evaluate the progression of atrial myopathy using biometric data, including volume changes in blood vessels, heart rate, and oxygen saturation. Using this data, the researchers aim to train a machine learning algorithm to predict cardiovascular outcomes and enable earlier interventions. In trials with low patient engagement, AI can also analyze engagement patterns and predict when a participant is at risk of dropping out. By ensuring consistent engagement and adherence, AI helps maintain the integrity of the trial data, leading to more reliable and valuable outcomes.

From Slow and Methodical to Dynamic: How AI Adds Jazz to Clinical Trials

The use of AI has opened new opportunities in designing personalized treatment plans and adaptive trial protocols. Researchers at Brigham and Women’s Hospital and Harvard T.H. Chan School of Public Health highlight that adaptive trials allow for prospectively planned changes to a trial, enhancing flexibility and responsiveness based on accumulating data. To properly utilize patient results and customize interventions, AI can process and analyze real-time data based on individual patient characteristics. AI algorithms identify subpopulations within a trial that respond differently to treatments, allowing for more targeted therapeutic approaches and reducing the number of patients in poorly performing treatment groups. This level of precision and adaptability can lead to better patient outcomes and a higher likelihood of trial success. It is important to note that the use of adaptive trials will require careful consideration of statistical validity and development of regulatory guidelines.

Several industry use cases further underscore the transformative potential of AI in clinical trial design. For instance, Unlearn.AI leverages digital twins—virtual models of patients created from historical data—to simulate trial outcomes and optimize designs. The use of digital twins has reduced the reliance on control groups and accelerated trial timelines. Unlearn’s study on Alzheimer’s Disease demonstrated that digital twins showed value in predicting clinical outcomes, allowing for a reduction in the number of required subjects by up to 35% for control arms and 21% for the overall study size. The AI-based digital twin methodology shortens trial duration while cutting down on costs and enhancing efficiency. Additionally, digital twins adhere to regulatory guidelines, ensuring that the accelerated timelines and reduced control group sizes do not sacrifice the reliability of traditional clinical trials.

 The Red Tape Tango: AI’s Dance with Regulations

While the use of AI in clinical trials shows significant promise, these innovations also highlight the growing need to address regulatory challenges. Traditional trial frameworks were not designed with AI in mind, leading to uncertainties around data privacy, algorithm transparency, and validation requirements. Ensuring that AI systems are transparent, and their decisions are explainable is crucial for maintaining the trust and ethical standards required for clinical trials. The absence of standardized guidelines complicates the regulatory landscape, making it difficult for sponsors and researchers to navigate the approval processes. Regulators across the EU, US, and UK are starting to acknowledge the urgency with which regulation is needed, and in May 2023, the FDA released a discussion paper soliciting feedback on the use of AI/ML in drug development. Addressing these regulatory challenges is paramount to fully capitalize on the benefits of AI in clinical trials.

Further collaboration between regulators, researchers, and AI developers can create a more conducive environment for innovation while ensuring patient safety and data integrity. Organizations like the Alliance for Artificial Intelligence in Healthcare (AAIH) are actively working towards establishing such standards. By working to establish clear guidelines and promoting dialogue among stakeholders, the AAIH seeks to ensure that AI is integrated safely and effectively across clinical trials and healthcare, benefiting patients and advancing medical research.

 AI’s Encore Performance

AI stands at the forefront of a paradigm shift in clinical trials, with the promise of enhancing efficiency and effectiveness. AI-driven tools can streamline data analysis, optimize patient recruitment, and enable adaptive trial designs more responsive to patient needs. Machine learning algorithms can sift through extensive datasets, identifying patterns and making predictions that inform more precise and personalized treatment plans. In addition, we need to keep an eye on ethical and community-focused adoption of AI.  To reach these goals, collaborative efforts and ongoing dialogue between stakeholders will be key to overcoming regulatory challenges and driving innovative and effective healthcare solutions – and active engagement in organizations like the Alliance for Artificial Intelligence in Healthcare will be crucial to facilitating productive outcomes.

____________________________________________________

The Tulane Medicine team, who is also the Tulane Digest Team, is partnering at BIO 2024 this week. You can send a request through the BIO partnering system, or email us directly to arrange a time to connect.

____________________________________________________

Recent Podcast Episode Drops:

Whether for travel entertainment or a quick listen between meetings, check out 6 recently released bite-size episodes of BIO from the BAYOU. Check them out on the BftB Website, Apple Podcasts, Spotify, or anywhere you podcast.

____________________________________________________ 

Share the Science: Please forward this issue and encourage others to sign up for Tulane School of Medicine’s Digest Mailing List.

____________________________________________________ 

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.

Eric Malamud, MBA, and Alexis L. Ducote, PhD: Editors-in-Chief

Special thanks to James Zanewicz, JD, LLM, RTTP and Elaine Hamm, PhD for copy-editing assistance.

Inhale, exhale: Life with interstitial lung disease

Imagine taking a breath and feeling your lungs fill with ease – a simple action we often take for granted, save for the occasional respiratory infection. But what if every single breath became a struggle, feeling like you were trying to draw air in through a tiny straw? This is the reality for the many individuals living with interstitial lung diseases (ILDs). These conditions, which lead to progressive scarring of lung tissue, make it increasingly difficult to breathe. Though they might not make headlines as frequently as diseases such as cancer or neurodegeneration, ILDs are widespread and significantly impact the lives of the nearly 5 million individuals they are estimated to affect worldwide.

A needle in a haystack: The diagnostic difficulty of ILDs

The category of interstitial lung diseases represents a diverse group of more than 200 lung disorders that primarily affect the lung’s interstitium, the tissue and space between air sacs of the lungs and the blood vessels which absorb oxygen for delivery to the rest of the body and deposit carbon dioxide back into the lungs for exhalation. Unlike other lung diseases that may affect the airways or blood vessels, ILDs are characterized by inflammation, scarring (fibrosis), and stiffening of the lung tissue, which can lead to severe breathing difficulties, chronic cough, impaired oxygen transfer, and constant fatigue. Despite their shared features, ILDs vary widely in their causes, clinical presentations, and outcomes. Some ILDs are idiopathic (meaning their cause is unknown), while others are linked to environmental exposures, medications, or underlying autoimmune diseases. Common types of ILDs include idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis, and sarcoidosis, each with distinct pathological and clinical characteristics. Identifying and understanding these differences is a crucial component of accurate diagnosis and effective treatment.

To untangle the knot, or slice clean through

Clinicians differentiate between various interstitial lung diseases through a comprehensive, multidisciplinary approach that integrates clinical, radiologic, and histopathologic data. The initial diagnostic step involves composing a detailed patient history, including occupational and environmental exposures, smoking habits, and drug use, which can help identify common causes like pneumoconiosis, drug-induced ILD, and hypersensitivity pneumonitis. High-resolution computed tomography (HRCT) of the chest is an often-employed diagnostic tool, capable of identifying definitive patterns indicative of idiopathic pulmonary fibrosis such as usual interstitial pneumonia. Serologic tests can identify connective tissue disease-associated ILDs, while bronchoalveolar lavage and lung biopsies, including transbronchial and video-assisted thoracoscopic biopsies, provide histological confirmation. The final diagnosis is typically made through a multidisciplinary discussion involving pulmonologists, radiologists, and pathologists, ensuring that clinical, radiologic, and histopathologic findings are properly interpreted.

Given the complexity of diagnosis of ILDs, the establishment of specialized centers for pulmonary fibrosis has been instrumental in improving patient outcomes and advancing the understanding of these debilitating diseases. The Pulmonary Fibrosis Foundation (PFF) has been at the forefront of this effort with the PFF Care Center Network (CCN), which it established in 2013. The network ensures that patients with pulmonary fibrosis have access to experienced medical professionals and comprehensive support services. The CCN has expanded to include 88 centers across the country, combining expertise in patient care and research. These centers work collaboratively to provide early diagnosis, cutting-edge treatments, and enhanced awareness of pulmonary fibrosis. Across the US, clinicians at institutions from UCSF Health in San Francisco to Tulane University’s Interstitial Lung Disease Center in New Orleans engage in clinical trials dedicated to advancing treatments for patients suffering from ILDs. Additionally, the network plays a vital role in facilitating research and advocating for the pulmonary fibrosis community, aiming to expedite scientific discoveries, develop effective therapies and ensure patient engagement in the process.

Current treatments for interstitial lung diseases include a variety of pharmacologic and non-pharmacologic strategies. Immunosuppressive agents such as corticosteroids, cyclophosphamide, mycophenolate mofetil, and azathioprine are commonly used, particularly in connective tissue disease-associated ILD. Approved in 2014, the antifibrotic agents nintedanib and pirfenidone have shown efficacy in slowing disease progression, especially in idiopathic pulmonary fibrosis and systemic sclerosis-associated ILD. Biologic therapies, including tocilizumab, have also been approved for specific ILD subtypes. But non-pharmacologic treatments, such as supplemental oxygen and cardiopulmonary rehabilitation, are just as integral to a comprehensive care plan. Finally, lung transplantation remains an option for advanced, progressive ILD unresponsive to other treatments. The choice of therapy is often individualized based on disease severity, progression, and patient-specific factors.

Turning back time: Reversal of fibrosis as a critical target

Unfortunately, the currently available treatments typically only slow the inexorable progression of fibrosis in many ILDs and do not cure existing damage. Normally, myofibroblasts—a cell type that forms in response to tissue injury and aids in tissue repair—undergo controlled cell death and are removed. In progressive fibrosing ILDs like IPF, these cells become resistant to clearance, depositing scar tissue and sending pro-inflammatory signals to nearby cells in an uncontrolled manner. While the recently approved standard-of-care drugs nintedanib and pirfenidone have shown efficacy in stabilizing disease in patients with IPF, these treatments do not reverse existing fibrosis.  Thankfully, there have been recent advances including the development of phosphodiesterase 4B inhibitors, which have shown promise in stabilizing pulmonary function in early trials (one instance of which is in ongoing trials by Boehringer Ingelheim), but further research is needed to confirm their efficacy and safety. The Thannickal Lab at the Tulane University School of Medicine is investigating potential gene silencing treatments which could reverse the cellular changes leading to collagen deposition in fibrosis. Additionally, a recent spin-out of the University of Washington School of Medicine’s Institute for Protein Design is developing a miniprotein binder to inhibit αvβ6 integrin, a protein that promotes fibrosis, and is currently carrying out Phase II trials. But even with these potential advances on the horizon, it is clear that further research and innovation are crucial to discovering effective treatments that can halt – and ideally reverse – fibrosis progression.

Advances and challenges in ILD

Significant progress in diagnosis and treatment has improved patient outcomes, but much work remains. Parsing the complex, heterogeneous collection of diseases under the ILD umbrella requires extensive knowledge and ongoing, strategic collaborations among multidisciplinary experts. Advances in medical research and artificial intelligence, along with improved diagnostic criteria, may help reduce the burden of initial disease characterization. However, there are still no remedies for existing lung damage. Specialized centers and collaborative research networks are advancing care and fostering innovation, offering hope for new treatments that can significantly improve the quality of life for those affected by ILD and their families.

 ____________________________________________________

The Tulane Medicine team, who is also the Tulane Digest Team, is partnering at BIO 2024 this week. You can send a request through the BIO partnering system, or email us directly to arrange a time to connect.

____________________________________________________

Recent Podcast Episode Drops:

Whether for travel entertainment or a quick listen between meetings, check out 6 recently released bite-size episodes of BIO from the BAYOU. Check them out on the BftB Website, Apple Podcasts, Spotify, or anywhere you podcast.

____________________________________________________ 

Share the Science: Please forward this issue and encourage others to sign up for Tulane School of Medicine’s Digest Mailing List.

___________________________________________________ 

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.

Alexis L. Ducote, PhD: Editor-in-Chief

Special thanks to James Zanewicz, JD, LLM, RTTP and Elaine Hamm, PhD for copy-editing assistance.

Recent reports about the detection of highly infective avian influenza (HPAI) in US livestock (a young goat, herds of dairy cattle) and even an individual in Texas have raised the specter of the SARS-COV2 pandemic, leading some to ask whether a new global incident is just around the corner. In today’s Tulane Medicine Digest, we will discuss the current state of the avian influenza outbreak, the CDC’s thoughts on risk to humans, and the available options for prevention and treatment of HPAI.

A Brief History of Avian Influenza

Avian influenza was first identified over a century ago, with initial reports dating back to 1878, but outbreaks remained sporadic and contained throughout most of the twentieth century. Beginning in the 1990s, the increasing density of poultry populations (as a result of intensive farming) has resulted in longer, more frequent waves. H5N1—the strain of highly pathogenic avian influenza A (HPAI) at the heart of current reports—was first detected in 1996. Like many viruses, avian influenza undergoes genetic reassortment—a process in which viruses exchange genetic material between variants over time—leading to mutations that can alter infectivity and transmission.. The current H5N1 outbreak began in 2020 in chickens and wild birds and likely occurred due to such mutations. Cases in North America began in late 2021, but were primarily restricted to domestic poultry and wild birds, with occasional cases in wild mammals.

The recent detection in U.S. non-poultry farm animals, and limited transmission to humans, has understandably led to some public concern. It is important to note that in the US, the only known cases so far involve a poultry worker in Colorado in 2022 and a cattle worker in Texas in April of 2024. In both cases, symptoms were mild and resolved after only a few days. While infections can potentially cause severe illness, the risk of a large outbreak remains low due to the difficulty of human-to-human transmission. A 2023 case in a Chilean man briefly raised alarms due to the presence of a mutation known to increase viral replication, but several further mutations would have been necessary for the virus to easily spread between humans. Overall, the Centers for Disease Control and Prevention (CDC) has thus maintained its judgment that the current strain of H5N1 poses little direct threat to humans. 

Environmental and Agricultural Impact of HPAI

A greater concern has been the potential impact of viral spread on livestock and endangered species. In addition to the direct deaths from avian influenza, large numbers of animals often need to be isolated or culled in order to prevent spread. Such measures can lead to large fluctuations in the prices of products – such as eggs or milk – due to disrupted supply chains and increased costs of surveillance. It is currently unknown exactly how the disease transmits, so this is the main question that would impact a potential future mammalian spread. Airborne transmission—a large factor in the rapid spread of SARS-COV2—would pose the greatest threat. However, a recent study observed that the highest concentration of virus in dairy cattle was found in the milk itself, suggesting that the primary route of spread between cows may be due to direct contact with contaminated gloves or milking machinery, rather than by breathing. While this indicates presence of the virus in milk, pasteurization has been shown to destroy the pathogen. Despite this data, out of an abundance of caution the FDA has recommended discarding products from symptomatic animals to further reduce risk.

Whether transmission is direct or airborne, the most effective method of combatting further spread is likely to be a widespread vaccination. However, many livestock producers are reluctant to employ vaccination due to difficulties in exporting vaccinated animals and concerns over spread via asymptomatic carriers. Thus, a concerted effort is necessary to develop other effective methods of containing infection, increase efficacy of vaccines, and work to change policy to facilitate global use of preventative –  rather than reactive – measures. 

Stopping the Spread: Prevention and Treatments for Avian Influenza

Health authorities including the CDC and World Health Organization (WHO) actively monitor outbreaks of avian flu, and such vigilance has been heightened in light of recent human cases. Public health measures implemented include surveillance, monitoring of exposed individuals, and stringent biosecurity measures to prevent further spread. The CDC emphasizes that the first lines of defense are avoiding contact with sick or dead animals, handling animal products with care, and ensuring food products like milk are pasteurized before consumption​. For individuals who are infected, antiviral treatments such as oseltamivir are recommended for both mild and serious cases, and are especially effective if administered early. It is perhaps also comforting to know that the CDC already maintains a stockpile of candidate vaccine viruses to aid in faster development of specific vaccines in the event of an outbreak. 

In addition to established treatments, researchers are also developing novel techniques with potential to combat HPAI infection and spread. USDA scientists recently discovered a protein that increases cellular antiviral response to various strains of avian influenza. Gene-editing techniques to increase expression of this protein could be leveraged to provide greater innate protection against avian influenza in poultry. Tulane researchers James McLachlan, PhD and Lisa Morici, PhD, have developed a novel vaccine adjuvant shown to increase vaccine efficacy against various pathogens. The adjuvant increases immunity at mucosal surfaces, such as those of the nose and mouth, which are often the source of both initial infection and airborne transmission. A team at Georgia State University is exploring the potential of 4′-fluoridine as a novel antiviral for treatment of influenza. As rapid mutations in influenza viruses can increase their resistance against existing antivirals, the compound could provide greater effectiveness against novel challenging variants of the virus. 

The Importance of Global Cooperation

While the threat to humans remains low at present, controlling infection and spread of a rapidly mutating and ubiquitous pathogen such as avian influenza requires concerted efforts on the part of scientists, governments, and agricultural producers. The World Organisation for Animal Health states in its One Health approach that international collaboration is critical, and that individuals and institutions must work together to prevent future pandemics and remove barriers to effective containment. In a timely podcast on avian flu, Tulane University’s Chad Roy, PhD, answers many questions about the disease and stresses that in order to prevent future pandemics there must be a paradigm shift away from simply responding to existing dangers as they arise, and towards proactive prevention of future pathogenic risks.

In conclusion, while the recent detections of HPAI raise concern, they are unlikely to signal the onset of a global outbreak akin to SARS-COV2. The CDC’s assessment underscores that the current risk to human health remains low, largely due to the virus’s limited ability to transmit between humans. Nonetheless, continued vigilance will be important, including enhanced surveillance, biosecurity measures, and ongoing research into effective treatments and preventive strategies. Taking into account lessons learned during the COVID pandemic, a comprehensive approach that involves global cooperation will be vital for managing current risks and preparing for future threats, ensuring the health of humans and the safety of our global food supply.

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Special thanks to James Zanewicz, JD, LLM, RTTP and Elaine Hamm, PhD for copy-editing assistance.

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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