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Introduction
In the world of medical advancements, there is an emerging field that holds the promise of revolutionizing disease treatment as we know it. Living drugs, also known as living medicines or cell therapies, are an innovative class of therapies that involve utilizing living cells to treat various diseases and conditions. From cancer to genetic disorders, living drugs offer a new frontier in medicine, paving the way for personalized and potentially curative treatments. In this article, we will explore the groundbreaking concept of living drugs, their potential applications, and the impact they may have on the future of disease treatment.
What are Living Drugs?
The field of living medicine is rapidly evolving, with ongoing research and development of new therapies. One promising area of research is the use of engineered bacteria as therapeutic agents. Scientists are exploring the use of these bacteria to produce and deliver drugs directly to the site of a disease, as well as to manipulate the microbiome to treat a range of conditions.
Living drugs refer to therapeutic interventions that utilize living cells or genetically modified cells to target and treat diseases at their core. Unlike traditional medications, which are often chemical-based and exert their effects through molecular interactions, living drugs involve cell-based therapies that are tailored to each patient’s specific condition. These cells can be derived from the patient’s own body or sourced from a donor.
“Living medicine” is a term used to describe the development of therapies that use living organisms, such as bacteria or viruses, to treat diseases. These therapies are often referred to as “living drugs” or “living cell therapies”.
One example of a living medicine is CAR-T cell therapy, which uses a patient’s own T-cells that have been genetically modified to target and attack cancer cells. Another example is fecal microbiota transplantation (FMT), which involves transferring fecal matter from a healthy donor to a patient with a diseased gut microbiome in order to restore a healthy balance of bacteria.
Another area of focus is the use of viruses as vectors for delivering gene therapies. Scientists are investigating the use of modified viruses to deliver healthy genes to cells in patients with genetic disorders, such as cystic fibrosis and sickle cell anemia.
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How Living Drugs Work
Living drugs function through various mechanisms, but one of the most notable approaches involves immunotherapy. This technique harnesses the body’s immune system to identify and attack specific disease targets. For example, Chimeric Antigen Receptor (CAR) T-cell therapy is a form of living drug that is currently making headlines for its effectiveness against certain types of blood cancers.
CAR-T therapy involves extracting a patient’s T cells (a type of immune cell), genetically modifying them to express specific receptors that recognize cancer cells, and then infusing these enhanced cells back into the patient’s body. This leads to a highly targeted and potent immune response against cancer cells, offering the potential for long-term remission and even cures.
Applications of Living Drugs
Living medicines have the potential to revolutionize medicine by providing targeted, personalized treatments that can be more effective and have fewer side effects than traditional treatments. However, there are also challenges associated with the use of living medicines, such as the risk of adverse reactions and the need for careful regulation to ensure safety and efficacy.
- Cancer Treatment: Living drugs are showing remarkable success in treating various types of cancer, particularly in cases where conventional therapies have failed. CAR-T therapy, in particular, has demonstrated impressive results in patients with leukemia and lymphomas.
- Genetic Disorders: Living medicines hold promise in addressing genetic disorders caused by single gene mutations. Gene therapies, a subset of living drugs, involve delivering corrected genetic material into a patient’s cells, potentially curing diseases that were previously untreatable.
- Autoimmune Diseases: In autoimmune conditions, where the body’s immune system mistakenly attacks its own tissues, living drugs may be employed to regulate and restore immune balance.
- Infectious Diseases: Living drugs can be engineered to target specific pathogens, opening new possibilities for combating infectious diseases like HIV and hepatitis.
Living Medicine” Treats Lung Infections
In a new study reported in Jan 2023, researchers developed a modified (non-pathogenic) version of Mycoplasma pneumoniae that attacks Pseudomonas aeruginosa—which is resistant to many types of antibiotics and is a common source of infections in hospitals. The modified M. pneumoniae was used in combination with low doses of antibiotics that would otherwise not work on their own.
The M. pneumoniae treatment significantly reduced lung infections in mice and doubled mouse survival rate compared to no treatment. Administering a single, high dose of the treatment showed no signs of toxicity in the lungs. And, once the treatment had finished its course, the immune system cleared the modified bacteria in a period of four days
This research is published in Nature Biotechnology in the paper, “Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms.”
P. aeruginosa infections are difficult to treat, in part, because the bacteria forms biofilms which have an increased resistance to antibiotics.
One particularly challenging infection occurs when biofilms grow on the surface of endotracheal tubes used by critically-ill patients who require mechanical ventilators to breathe. This causes ventilator-associated pneumonia (VAP), a condition that affects one in four (9–27%) patients who require intubation. The incidence exceeds 50% for patients intubated because of severe COVID-19. VAP can extend the duration in the intensive care unit for up to thirteen days and kills up to one in eight patients (9–13%).
In this study, M. pneumoniae was engineered to dissolve biofilms by equipping it with the ability to produce various molecules including pyocins—toxins naturally produced by bacteria to kill or inhibit Pseudomonas. To test its efficacy, they collected P. aeruginosa biofilms from the endotracheal tubes of patients in intensive care units. They found the treatment penetrated the barrier and successfully dissolved the biofilms.
“We have developed a battering ram that lays siege to antibiotic-resistant bacteria. The treatment punches holes in their cell walls, providing crucial entry points for antibiotics to invade and clear infections at their source. We believe this is a promising new strategy to address the leading cause of mortality in hospitals,” said María Lluch, PhD, staff scientist in the lab of Luis Serrano Pubul, PhD, at the Centre for Genomic Regulation (CRG) at the Catalan Institution for Research and Advanced Studies (ICREA) in Barcelona, Spain, and CSO at Pulmobiotics.
M. pneumoniae is one of the smallest known bacterial species. With just 684 genes and no cell wall, the relative simplicity of M. pneumoniae makes it ideal for manipulation. One of the advantages of using M. pneumoniae to treat respiratory diseases is that it is naturally adapted to lung tissue.
“The bacterium can be modified with a variety of different payloads—whether these are cytokines, nanobodies, or defensins. The aim is to diversify the modified bacterium’s arsenal and unlock its full potential in treating a variety of complex diseases,” said Serrano.
Challenges and Future Prospects
While living drugs offer exciting prospects, they also present challenges that must be addressed for their widespread adoption:
- Cost and Accessibility: Living drugs are currently expensive and complex to manufacture, making them inaccessible to many patients. Advancements in technology and streamlined manufacturing processes are essential to reducing costs and increasing accessibility.
- Safety Concerns: As living drugs involve altering a patient’s cells, there are potential risks associated with unintended side effects and immune reactions. Extensive clinical trials and ongoing monitoring are crucial to ensuring patient safety.
- Personalization and Compatibility: Each living drug is tailored to an individual patient, necessitating precision in their preparation. Ensuring compatibility and scalability will be vital as living drug therapies become more mainstream.
Despite the potential benefits of living medicines, there are also ethical considerations to be addressed. For example, there are concerns about the use of animals in the development and testing of living medicines, as well as the potential for unintended consequences of altering the microbiome or introducing genetically modified organisms into the environment.
Overall, the development of living medicines is an exciting area of research with the potential to transform the way we treat a range of diseases. However, careful consideration and regulation are needed to ensure the safety and efficacy of these therapies.
Conclusion
Living drugs represent a revolutionary approach to disease treatment, offering hope for patients facing previously incurable conditions. With ongoing research and development, the potential of living medicines seems boundless. As technology advances, we can expect living drugs to become more accessible, affordable, and effective across a broad range of diseases.
The collaboration between medical researchers, pharmaceutical companies, and regulatory authorities will play a pivotal role in bringing living drugs into mainstream healthcare. As we witness the transformative impact of living medicines, we can look forward to a future where personalized and curative therapies become the norm, enhancing the quality of life for countless patients worldwide.
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