Publisher Health

Medical technology innovations achieved by integrating science and medicine have improved the quality of life for patients. Especially noteworthy is the emergence of electronic devices implanted in the body, such as in the heart or brain, which enable real-time measurement and regulation of physiological signals, presenting new solutions for challenging conditions like Parkinson’s disease. However, technical constraints have hindered the semi-permanent use of electronic devices after their implantation.
A collaborative research team led by Professor Sung-Min Park from the Departments of Convergence IT Engineering, Mechanical Engineering, and Electrical Engineering, and the School of Interdisciplinary Bioscience and Bioengineering at POSTECH, alongside Jiho Lee, enrolled in the MS/Ph.D. program, and Professor Sang-Woo Kim from Yonsei University’s Department of Materials Science and Engineering, together with Dr. Young-Jun Kim and MS/Ph.D. student Joon-Ha Hwang from Sungkyunkwan University, has achieved a groundbreaking development. They’ve created electrostatic materials that function even with extremely weak ultrasound, heralding the era of permanent implantable electronic devices in biomedicine. This research has been published in the international academic journal Advanced Materials.
Patients with implanted devices need to undergo periodic surgeries for battery replacement. This process carries a significant risk of complications and imposes both economic and physical burdens on patients. Recent research explores implantable medical devices that operate wirelessly, yet finding a safe energy source and protective materials remains challenging. Presently, titanium (Ti) is used due to its biocompatibility and durability. However, radio waves cannot pass through this metal, necessitating a separate antenna for wireless power transmission. Consequently, this enlarges the device size, creating more discomfort for patients.
The research team addresses this issue by opting for ultrasound, a safety-validated method in various medical fields for diagnoses and treatments, instead of radio waves. They developed an electrostatic material capable of responding to weak ultrasound by utilizing a composite of high dielectric polymers (P(VDF-TrFE)) and a high dielectric constant ceramic material known as calcium copper titanate (CCTO, CaCu3Ti4O12). This material generates static electricity through friction between its material layers, producing effective electrical energy, and possesses an extremely low output impedence, facilitating efficient transmission of the generated electricity.
Using this technology, the research team created an implantable neurological stimulator powered by ultrasound-based energy transmission, eliminating the need for batteries. This was confirmed through experimental validation. In animal model trials, the device was activated even at standard imaging ultrasound levels (500 mW/cm2), imposing minimal strain on the human body. Furthermore, it effectively mitigated symptoms related to abnormal urination caused by overactive bladder disorders through nerve stimulation.
Professor Sung-Min Park stated: “We have addressed the challenges in the field of implantable medical devices using ultrasound-based energy transmission technology that is harmless to the human body. This research serves as a case of introducing advanced material technology into medical devices, and we anticipate that it will promote the emergence of a next-generation medical industry, including the treatment of intractable diseases using implantable devices.”
Professor Sang-Woo Kim remarked: “Devices manufactured based on highly biocompatible materials exhibit excellent mechanical and chemical stability, making them suitable for treating various diseases requiring long-term therapy. Non-battery, miniaturized components with established long-term stability are expected to bring forth new innovations in the market of human-insertable medical devices.”
The research was conducted with support from the Research Leader Program, Pioneer Program of Future Technology, and Bio & Medical Technology Development Program by the National Research Foundation of Korea and the Ministry of Science and ICT, along with Yonsei Fellowship.

People who are hard of hearing spend more energy listening. That energy comes at the expense of other cognitive functions. Cognitive functions are the mental processes in the brain that enable us to think and solve problems, among other things.
In a new study featuring data from 573,088 people, researchers from the Department of Clinical Research at the University of Southern Denmark have found a link between hearing loss and the development of dementia. The study is the largest of its kind to date.
There is already an increase in the number of people with dementia. This is mainly due to the ageing of the population as a whole, but there are also other risk factors, such as lifestyle and hearing.
“Previous studies have suggested that there could be a link between hearing loss and dementia. Our study is larger than the previous studies, and we have demonstrated a link between hearing loss and dementia, “says Assistant Professor Manuella Lech Cantuaria from the Department of Clinical Research at the University of Southern Denmark.
Good news for hearing aid users
The results of the study show that people affected by hearing loss have up to a 13% higher risk of developing dementia compared to people with normal hearing. The high risk is especially seen in people with severe hearing loss.
The researchers also studied whether there was a difference in the risk depending on whether or not people wear hearing aids.

“We found that the risk of developing dementia was 20% higher for people who didn’t wear hearing aids compared to people with normal hearing. People who used hearing aids had a 6% increased risk of developing dementia. This suggests that wearing a hearing aid can prevent or delay the development of dementia,” explains Manuella Lech Cantuaria.
About the study
The study is a so-called cohort study that follows a group of people with common characteristics over a longer period of time. In this study, all of the people were above 50 years of age and from the Region of Southern Denmark between 2003-2017. People diagnosed with dementia before the commencement of the study were excluded. The researchers compared data on people’s hearing with data on the development of dementia during the period. The researchers have found a significant — that is, clear — correlation between hearing loss and the development of dementia. The greatest risk of developing dementia was especially seen in people with severe hearing loss Hearing loss causes a 7% increased risk of developing dementia People with severe hearing loss have up to a 20% increased risk of developing dementia compared to people without hearing lossHearing loss and dementia
Hearing loss — a national scourge
Around 800,000 Danes suffer from hearing loss. And that number is only likely to get higher in the future because we are getting older in general, and we are exposed to more and more noise. Hearing loss is measured in decibels (dB). There are different degrees of hearing loss. For example, hearing loss above 60-70 dB means you can’t hear normal speech. Above 90-100 dB means you can’t hear shouting.
Dementia
Dementia is a term used to describe the weakening of mental abilities due to illness in the brain. Dementia is characterised by an impairment of cognitive functions such as: Impaired memory and concentration, impaired orientation, language disorders, personality and behavioural changes. Alzheimer’s, for example, is a type of dementia.

In a scientific breakthrough that aids our understanding of the internal wiring of immune cells, researchers at Monash University in Australia have cracked the code behind IKAROS, an essential protein for immune cell development and protection against pathogens and cancer.
This disruptive research, led by the eminent Professor Nicholas Huntington of Monash University’s Biomedicine Discovery Institute, is poised to reshape our comprehension of gene control networks and its impact on everything from eye colour to cancer susceptibility and design of novel therapies.
The study, published in Nature Immunology, promises pivotal insights into the mechanisms safeguarding us against infections and cancers. When the transcription factor Ikaros/Ikzf1 was deliberately obstructed, be it in preclinical models or humans, the once-mighty activity of Natural Killer (NK) cells, our immune system’s frontline warriors, plummeted. Loss of this transcription factor in NK cells resulted in wide-spread dysregulation of NK cell development and function, preventing their ability to recognize and kill virus-infected cells and clear metastatic tumour cells from circulation. Aiolos/Ikzf3 and Helios/Ikzf2, related family member were found to partial compensate for the loss of Ikaros, as such when multiple IKZF-family members were inhibited, NK cells underwent rapidly death. Mechanistically, Aiolos and Ikaros were found to directly bind and activate most members of the JUN/FOS family, transcription factors known for their essential roles in human embryo development and tissue function.
This discovery opens the door to the prospect of potential novel cancer therapeutics. NK cells, our first line of defence against pathogens and internal threats like cancers, could be fortified by therapies enhancing their killing prowess by targeting IKAROS and JUN/FOS biology.
Professor Huntington notes that drugs targeting IKAROS/AIOLOS have already received approval from the US Food and Drug Administration (FDA) and local Therapeutic Goods Administration (TGA) for the treatment of B cell malignancy “but until now we haven’t understood how these drugs work, armed with this new information it could be possible to develop novel drugs targeting these complexes which may offer differentiated pharmacology and therapeutic index for treating disease,” he said. Importantly on this front, Professor Huntington’s team were able to show that IKAROS had a conserved role in healthy B cells and thus potentially B cell cancers.

Creating a functional lung using interspecies chimeric animals is an attractive albeit challenging option for lung transplantation, requiring more research on the viable conditions needed for organ generation. A new study uses reverse-blastocyst complementation and tetraploid-based organ complementation methods to first determine these conditions in lung-deficient mice and then to generate rat-derived lungs in these mice. It provides useful insights on the intrinsic species-specific barriers and factors associated with lung development in interspecies chimeric animals.
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. It is marked by lung damage that is lasting and incurable, leaving lung transplantation as the only viable treatment option. Unfortunately, finding suitable lung donors is difficult. To compensate for this shortage of donors, regenerative medicine is making strides in developing lungs from pluripotent stem cells (PSCs), using interspecies animal models.
Through a biological technique known as blastocyst complementation, PSCs, and embryonic stem cells (ESCs) from one species can be injected into blastocysts of a different organ-deficient species, creating interspecies chimeric animals. This technique has enabled successful regeneration of the pancreas, heart, and kidney in rat-mouse chimeras. However, functional lung formation has still not been achieved successfully, warranting further research into the viable conditions required to generate PSC-derived organs.
Now, scientists from Nara Institute of Science and Technology (NAIST), Japan have used the reverse-blastocyst complementation (rBC) method to understand the conditions required to form lungs in rat-mouse chimeric models. In addition, they used the tetraploid-based organ complementation (TOC) method to successfully create a rat-derived lung in their mouse model. The study, published in Development, was led by Shunsuke Yuri and Ayako Isotani from NAIST.
The fibroblast growth factor 10 (Fgf10) and its interaction with the Fgf receptor 2 isoform IIIb (Fgfr2b) in the lungs are crucial for lung development. In this study, the rBC method involved injecting mutant ESCs which fail to show lung formation into wild-type (WT) embryos. This method allows for efficient detection of mutant PSCs in the recipient tissue, aiding the determination of the conditions necessary for successful lung formation in the organ-deficient animal.
The research team also found that WT ESCs provide uniform contributions across target and non-target organs in the chimeras. This helped ascertain that a certain number of WT or normal cells are required to overcome the lung development failure in Fgf10-deficient or Fgfr2b-deficient animals.
With this knowledge, they successfully produced rat-derived lungs in the Fgfr2b-deficient mouse embryos with the TOC method, without needing to produce a mutant mouse line. “Interestingly, we found that the rat epithelial cells conserved intrinsic species-specific timing in the interspecies model, resulting in an underdeveloped lung,” notes Yuri. Consequently, these lungs remained nonfunctional post-birth.
The findings of this study clearly identify the factors required and barriers to overcome for successful generation of functional lungs in rat-mouse interspecies chimeras. Speaking of the significance of these findings, Yuri concludes, “We believe that our study makes an important contribution to the literature by presenting a faster and more efficient method of exploring blastocyst complementation. These novel results can significantly advance the progress toward developing in-vivo chimeric lungs for the purpose of transplantation, which could transform the practical application of regenerative medicine.”

Freezing is one of the most common and debilitating symptoms of Parkinson’s disease, a neurodegenerative disorder that affects more than 9 million people worldwide. When individuals with Parkinson’s disease freeze, they suddenly lose the ability to move their feet, often mid-stride, resulting in a series of staccato stutter steps that get shorter until the person stops altogether. These episodes are one of the biggest contributors to falls among people living with Parkinson’s disease.
Today, freezing is treated with a range of pharmacological, surgical or behavioral therapies, none of which are particularly effective.
What if there was a way to stop freezing altogether?
Researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Boston University Sargent College of Health & Rehabilitation Sciences have used a soft, wearable robot to help a person living with Parkinson’s walk without freezing. The robotic garment, worn around the hips and thighs, gives a gentle push to the hips as the leg swings, helping the patient achieve a longer stride.
The device completely eliminated the participant’s freezing while walking indoors, allowing them to walk faster and further than they could without the garment’s help.
“We found that just a small amount of mechanical assistance from our soft robotic apparel delivered instantaneous effects and consistently improved walking across a range of conditions for the individual in our study,” said Conor Walsh, the Paul A. Maeder Professor of Engineering and Applied Sciences at SEAS and co-corresponding author of the study.
The research demonstrates the potential of soft robotics to treat this frustrating and potentially dangerous symptom of Parkinson’s disease and could allow people living with the disease to regain not only their mobility but their independence.

The research is published in Nature Medicine.
For over a decade, Walsh’s Biodesign Lab at SEAS has been developing assistive and rehabilitative robotic technologies to improve mobility for individuals’ post-stroke and those living with ALS or other diseases that impact mobility. Some of that technology, specifically an exosuit for post-stroke gait retraining, received support from the Wyss Institute for Biologically Inspired Engineering, and was licensed and commercialized by ReWalk Robotics.
In 2022, SEAS and Sargent College received a grant from the Massachusetts Technology Collaborative to support the development and translation of next-generation robotics and wearable technologies. The research is centered at the Move Lab, whose mission is to support advances in human performance enhancement with the collaborative space, funding, R&D infrastructure, and experience necessary to turn promising research into mature technologies that can be translated through collaboration with industry partners.
This research emerged from that partnership.
“Leveraging soft wearable robots to prevent freezing of gait in patients with Parkinson’s required a collaboration between engineers, rehabilitation scientists, physical therapists, biomechanists and apparel designers,” said Walsh, whose team collaborated closely with that of Terry Ellis, Professor and Physical Therapy Department Chair and Director of the Center for Neurorehabilitation at Boston University.
The team spent six months working with a 73-year-old man with Parkinson’s disease, who — despite using both surgical and pharmacologic treatments — endured substantial and incapacitating freezing episodes more than 10 times a day, causing him to fall frequently. These episodes prevented him from walking around his community and forced him to rely on a scooter to get around outside.

In previous research, Walsh and his team leveraged human-in-the-loop optimization to demonstrate that a soft, wearable device could be used to augment hip flexion and assist in swinging the leg forward to provide an efficient approach to reduce energy expenditure during walking in healthy individuals.
Here, the researchers used the same approach but to address freezing. The wearable device uses cable-driven actuators and sensors worn around the waist and thighs. Using motion data collected by the sensors, algorithms estimate the phase of the gait and generate assistive forces in tandem with muscle movement.
The effect was instantaneous. Without any special training, the patient was able to walk without any freezing indoors and with only occasional episodes outdoors. He was also able to walk and talk without freezing, a rarity without the device.
“Our team was really excited to see the impact of the technology on the participant’s walking,” said Jinsoo Kim, former PhD student at SEAS and co-lead author on the study.
During the study visits, the participant told researchers: “The suit helps me take longer steps and when it is not active, I notice I drag my feet much more. It has really helped me, and I feel it is a positive step forward. It could help me to walk longer and maintain the quality of my life.”
“Our study participants who volunteer their time are real partners,” said Walsh. “Because mobility is difficult, it was a real challenge for this individual to even come into the lab, but we benefited so much from his perspective and feedback.”
The device could also be used to better understand the mechanisms of gait freezing, which is poorly understood.
“Because we don’t really understand freezing, we don’t really know why this approach works so well,” said Ellis. “But this work suggests the potential benefits of a ‘bottom-up’ rather than ‘top-down’ solution to treating gait freezing. We see that restoring almost-normal biomechanics alters the peripheral dynamics of gait and may influence the central processing of gait control.”
The research was co-authored by Jinsoo Kim, Franchino Porciuncula, Hee Doo Yang, Nicholas Wendel, Teresa Baker and Andrew Chin. Asa Eckert-Erdheim and Dorothy Orzel also contributed to the design of the technology, as well as Ada Huang, and Sarah Sullivan managed the clinical research. It was supported by the National Science Foundation under grant CMMI-1925085; the National Institutes of Health under grant NIH U01 TR002775; and the Massachusetts Technology Collaborative, Collaborative Research and Development Matching Grant.

The cycling of water across membrane transporters is an hallmark of the cell metabolism and is potentially of high diagnostic significance for the characterization of tumors and other diseases. In the journal Angewandte Chemie, an Italian research team has now introduced a new MRI-based method for assessing this water exchange. By this method, they were able to estimate the degree of malignancy and the success of treatments in mice tumor models.
Not all cancers are equal. Depending on the type of tumor, a given treatment may be spot on or fail completely. For targeted, effective, treatment that is as gentle as possible, it is important to precisely locate the tumor and determine its malignancy. Magnetic resonance imaging (MRI) provides excellent time- and spatially resolved images for the characterization of tumors. During this procedure, the patient lies in a “tube” in which there is a very strong magnetic field. The spins of protons (the nuclei of hydrogen atoms) align themselves in this magnetic field. Radio waves are beamed in and synchronize the precessions of the spins, temporarily flipping some of them. Depending on the composition of the tissue, this “magnetization” is lost at different times (relaxation). This can be used to compute 3D images. Gadolinium contrast agents reduce the relaxation times. These agents are more concentrated in tumors because their blood vessels are particularly permeable. This increases the contrast and makes it easier to define the tumor.
Contrast agents only spread through the extracellular compartments of the tumor; they do not enter tumor cells. A team led by Giuseppe Ferrauto and Silvio Aime wanted to exploit this feature to determine the degree of water exchange through the cell membrane. Tumor cells are more metabolically active than healthy cells and have more transport proteins and channels in their cell membranes. These proteins also allow water to enter and exit the cell, and the degree of water exchange is a measure of the aggressiveness of a tumor. Yet, classic MRI cannot show this.
The team from the University of Torino and IRCCS SDN SynLab in Naples decided to work with a new MRI method called CEST (Chemical Exchange Saturation Transfer). There is constant proton exchange between free water and hydrogen-containing groups in biomolecules, such as the amine groups in creatine. The radio frequencies at which a proton can be “magnetized” depends on the chemical environment of that proton, so frequencies are different for protons in free water and those bound to creatine, for example. With a matching pulse, the creatine-bound protons can be saturated. These protons are exchanged and bind to nearby free water. They keep their “saturated magnetization state” as they do this. If radio waves with the right frequency for free water protons are then pulsed, an increasing number of these protons are already magnetized and cannot absorb the energy (the CEST signal in MR images). Absorption decreases until the proton exchange reaches equilibrium. This makes it possible to draw conclusions about the concentration of creatine and other proton exchanging molecules in a cell, which can be used for cancer phenotyping.
If a contrast agent is then administered and enters the extracellular compartment, the magnetization of the water protons there decreases significantly faster. Because water is exchanged through the membrane, the number of magnetized water protons within the cells also decreases more quickly. This in turn changes the CEST signals. The changes after addition of contrast agent reflect the permeability of the tumor cell membrane to water.
The team tested this method in mouse models for breast cancer with different degrees of malignancy. As expected, the observable water exchange increase as the tumors grew more aggressive. Within the tumors, it was also possible to differentiate between areas of differing malignancy. The cytostatic drug Doxorubicin immediately reduced the water permeability.
Hence, the developed method sheds light into tumor phenotype and provides a new tool to assess the outcome of chemotherapy.

A new study in Advanced Science unlocks the secrets of how high blood pressure (hypertension) fuels the progression of arterial disease. Led by Professor Thomas Iskratsch, Professor of Cardiovascular Mechanobiology & Bioengineering at Queen Mary University of London, the research team exposes a novel mechanism by which elevated pressure transforms muscle cells in the arterial wall into “foam cells” — the building blocks of plaque buildup that cripples arteries.
The study focuses on vascular smooth muscle cells (VSMCs), the workhorses responsible for maintaining blood vessel tone and flow. Under the chronic stress of hypertension, VSMCs undergo a dramatic makeover. The researchers discovered that pressure alone triggers these cells to fill with lipid droplets, morphing them into foam cells — culprits in the formation of atherosclerotic lesions, the hallmark of arterial disease.
“This finding is pivotal because VSMCs make up over half of the foam cells found in arterial blockages,” explains Professor Iskratsch. “Understanding how pressure flips this switch from muscle to foam cell is crucial for developing new therapies to control or reverse the buildup of these dangerous lesions.”
The study goes deeper, identifying the molecular machinery behind pressure’s impact. Using advanced imaging techniques, researchers pinpointed a “mechanosignalling” pathway involving Piezo1, a pressure-sensitive protein, as well as changes in lipid metabolism and gene activity. This paves the way for novel therapies targeting specific pressure-sensitive points in the cell.
This breakthrough research offers not only a deeper understanding of arterial disease but also exciting possibilities for future treatment strategies. By targeting the mechanisms that drive VSMC transformation into foam cells, researchers might be able to develop medications that prevent or even shrink atherosclerotic lesions.
“Our findings provide a vital blueprint for developing next-generation therapies that could benefit millions suffering from the life-threatening consequences of arterial disease,” concludes Professor Iskratsch. “This is a significant step forward in our journey towards a future where high blood pressure doesn’t have to steal away life.”

The pathogenic potential of inhaling the inert fibrous nanomaterials used in thermal insulation (such as asbestos or fibreglass) is actually connected not to their chemical composition, but instead to their geometrical characteristics and size. This was revealed by a study, published on 3 January 2024 in the journal Nature Nanotechnology, conducted on glass nanofibers by a French-Chinese team including a CNRS chemist.1
The reason for this is the inability of the macrophages2 naturally present in pulmonary alveolar tissue to eliminate foreign bodies that are too large. The study was initially conducted in vitro with electrochemical nanosensors, and revealed that when confronted with inert nanofibers over 15 microns in length,3 the cells are unable to distend enough to entirely encapsulate them within their “digestive” vesicle. This results in leaked secretions that are very harmful for the alveolar walls, which this study detected, characterised, and quantified for the first time.4 An experiment on rats subsequently showed that regular unprotected inhalation of similar inert fibrous nanometerials, whatever they may be, causes repeated pulmonary lesions that can eventually lead to the development of fibroma.
This discovery poses a challenge for the use of inert nanofibre felts in construction, which had heretofore been deemed to be less harmful than the asbestos it replaced, but that in reality could present the same health risks for those handling it.
Notes :
1 From the Selective Activation Processes via Uni-Electronic or Radiative Energy Transfer Laboratory (CNRS/ École normale supérieure — PSL/Sorbonne Université), in collaboration with Wuhan University.
2″Big eater” cells belonging to groups of white blood cells whose primary role is to eliminate cell debris and pathogenic biological agents throughout the body.
3 Or 0.015mm, a micron measuring 10-3 mm.
4 The ROS and RNS species (species reactive to oxygen and nitrogen) secreted by macrophages are known for attacking the bioorganic components of healthy cells, and cause inflammation and mutations that are often cancerous. While the phenomenon of “frustrated phagocytosis” had already been observed, its role in the pathogenesis of the concerned diseases had not yet been clearly established.

Scientists at St. Jude Children’s Research Hospital are tackling Mycobacterium abscessus (Mab) antibiotic resistance. This naturally antibiotic-resistant pathogen is becoming more prevalent, highlighting the urgent need for novel therapeutics. To address this, the scientists designed new versions of the drug spectinomycin that overcome efflux, the main mechanism driving resistance. The work was published today in Proceedings of the National Academy of Science.
Mab infections are increasingly found in health care settings. Such infections can be hazardous for patients with compromised lung function, such as in cystic fibrosis, or who are immunologically compromised, such as in childhood cancer. These infections are treated with long courses of antibiotics and can result in poor outcomes. The emergence of Mab and other similar pathogens presents a growing and deeply concerning public health threat because there are few effective therapeutic options and a limited drug development pipeline.
“We chemists are in a race against the pathogens. We make stronger antibiotics, and the pathogens become more resistant,” said corresponding author Richard Lee, PhD, St. Jude Department of Chemical Biology and Therapeutics.
Scientists at St. Jude modified the naturally occurring antibiotic spectinomycin to create analogs, comparable but structurally distinct N-ethylene linked aminomethyl spectinomycins (eAmSPCs). These synthetically created eAmSPCs are up to 64 times more potent against Mab than standard spectinomycin.
“By re-engineering the molecule through structure-based drug design, we and our collaborators have adapted the antibiotic to increase its activity,” Lee added.
Overcoming efflux to make a more effective antibiotic
Through their work, the scientists unraveled the mechanism of action by which eAmSPCs are more effective: they circumvent efflux. Efflux is the process that cells use to get rid of a drug — imagine pumping water out of a flooded basement — and is a significant mechanism by which cells become resistant to therapy.

The N-ethylene linkage structure of the eAmSPCs plays a critical role in how the compounds avoid efflux, suggesting that longer linkages modify how the compound is pumped out of the cell. This ultimately shifts the balance toward higher concentrations of eAmSPC within the cell and thus enhances antimicrobial efficacy.
“Over the past two decades, we’ve seen a massive increase in the number of infections caused by non-tuberculous mycobacteria like Mab,” said co-first author Gregory Phelps, PharmD, St. Jude Graduate School of Biomedical Sciences. “We had a place to start with this naturally occurring antibiotic, which, through modification, we’ve made much more efficacious against this clinically relevant pathogen.”
The researchers also found that eAmSPCs work well with various classes of antibiotics used to treat Mab and retain their activity against other mycobacterial strains. Collectively, this work demonstrates that eAmSPCs should be further studied and developed because once issues of tolerability and safety are addressed, these compounds could become next-generation therapeutics.
“It is challenging to attract pharmaceutical companies to develop new antibiotics for several economic reasons,” said Phelps. “If we can boost the drug pipeline against this hard-to-treat bacteria, we can potentially make a difference for patients like the ones we have here at St. Jude who are increasingly faced with limited or no therapeutic options.”

The agency plans to authorize Florida to purchase medicines directly from wholesalers in Canada, where prices are far cheaper. Pharmaceutical companies oppose the plan.The Food and Drug Administration has decided to allow Florida to import millions of dollars worth of medications from Canada at far lower prices than in the United States, overriding fierce decades-long objections from the pharmaceutical industry, according to a senior administration official.The approval is a major policy shift for the United States, and supporters hope it will be a significant step forward in the long and largely unsuccessful effort to reign in drug prices. Individuals in the United States are allowed to buy directly from Canadian pharmacies, but states have long wanted to be able to purchase medicines in bulk for their Medicaid programs, government clinics and prisons from Canadian wholesalers.Florida has estimated that it could save up to $150 million in its first year of the program, importing medicines that treat H.I.V., AIDS, diabetes, hepatitis C and psychiatric conditions. Other states have applied to the F.D.A. to set up similar programs.But significant hurdles remain. The pharmaceutical industry’s major lobbying organization, the Pharmaceutical Research and Manufacturers of America, or PhRMA, which has sued over previous importation efforts, is expected to file suit to prevent the Florida plan from going into effect. Some drug manufacturers have agreements with Canadian wholesalers not to export their medicines, and the Canadian government has already taken steps to block the export of prescription drugs that are in short supply.“Canada’s drug supply is too small to meet the demands of both American and Canadian consumers,” Maryse Durette, a spokeswoman for Health Canada, wrote in an email message. “Bulk importation will not provide an effective solution to the problem of high drug prices in the U.S.”Congress passed a law allowing drug importation two decades ago, but federal health officials delayed implementing it for years, citing safety concerns, one of the main arguments drug companies have used against it. In 2020, President Donald J. Trump pushed the law forward, announcing that states could submit importation proposals to the F.D.A. for review and authorization. President Biden added momentum the following year, instructing federal officials to keep working with states on importation plans.Florida applied and later sued the F.D.A., accusing the agency of what Gov. Ron DeSantis called a “reckless delay” in approving the request. Friday’s announcement grew out of that lawsuit; a federal judge had set a Jan. 5 deadline for the F.D.A. to act on the state’s application.Eight other states — Colorado, Maine, New Hampshire, New Mexico, North Dakota, Texas, Vermont and Wisconsin — have laws allowing for a state drug importation program, and many are seeking, or planning to seek, F.D.A. approval.Colorado’s application is pending with the F.D.A. New Hampshire’s application was rejected last year. Vermont’s was deemed incomplete; a spokeswoman said the state was waiting to see how the F.D.A. handled the applications by other states before resubmitting.Colorado officials have signaled that states may face challenges to their importation plans from drugmakers in Canada, among them familiar names like Pfizer, Merck and AstraZeneca. Some drugmakers have written contracts with drug-shipping companies prohibiting deliveries to the United States, Colorado officials said in a report.Drug importation has broad political and public support. A 2019 poll by KFF, a nonprofit health research group, found that nearly 80 percent of respondents favored importation from licensed Canadian pharmacies.“Importation is an idea that resonates with people,” Meredith Freed, a senior policy analyst with KFF, said. “They don’t fully understand why they pay more for the same drug than people in other countries.”With the 2024 presidential election on the horizon, candidates are looking to claim credit for efforts to reduce drug prices. President Biden is spotlighting the Inflation Reduction Act, which empowers Medicare to negotiate prices directly with drugmakers for the first time, but only for a limited number of high cost medicines. Mr. DeSantis, who is challenging Mr. Trump for the Republican nomination, is touting his import plan.Several experts in pharmaceutical policy said that importation from Canada would not address the root cause of high drug prices: the ability of pharmaceutical makers to fend off generic competition by gaming the patent system, and the federal government’s broad failure to negotiate directly with drugmakers over cost.“Seems like political theater to me, where everyone wants to say they did something to drive down the price of prescription drugs,” Nicholas Bagley, a health law expert at the University of Michigan Law School, said of Florida’s plan.Both Mr. Bagley and Dr. Aaron Kesselheim, a professor of medicine at Harvard Medical School, said that the Inflation Reduction Act is a more direct path to lowering prices; the law’s price negotiation provisions are expected to save the federal government an estimated $98.5 billion over a decade. Drugmakers are suing to block those provisions from taking effect.A protest outside the Pharmaceutical Research and Manufacturers of America in Washington in 2021. PhRMA is likely to file suit to prevent any plan from going into effect.Saul Loeb/Agence France-Presse — Getty ImagesWith its approval in hand, Florida has more work to do. Before it can distribute Canadian drugs, the state must send the F.D.A. details on those it plans to import. The state has to ensure that the drugs are potent and not counterfeit. It also must put F.D.A.-approved labels on medications instead of those used in Canada.The F.D.A. said it would be watching to see if the state upholds safety rules — such as the reporting of any drug side effects — and delivers significant cost savings to consumers. Florida’s approval to import lasts for two years from the date of the first drug shipment.In Canada, health officials have been casting a wary eye on the push to import from their country. In November 2020, shortly after the Trump administration announced that states could submit importation proposals, the Canadian government published its own rule to prevent manufacturers and wholesalers from exporting some drugs that are in short supply.The Canadian government is likely to further restrict exports if they begin to affect Canadians, said Amir Attaran, a law professor at the University of Ottawa. He said the numbers don’t work out for a nation of nearly 40 million to supply medications for a state with 22 million people, much less for 49 other U.S. states.“If all of a sudden Florida is able to extend a vacuum cleaner hose into this country to take what’s in the medicine chest, the supply disruption will be a completely different category,” he said. Dr. Kesselheim, of Harvard, said the F.D.A.’s authorization was unlikely to make a difference in the price of very expensive brand-name drugs, because manufacturers would block wholesalers from exporting the medicines.“I think it’s going to be hard for states to import drugs like that in any kind of scale that would make a difference in terms of lowering prices for patients,” Dr. Kesselheim said. Even so, he said, the F.D.A.’s announcement is significant because it puts to rest the notion that drug importation cannot be accomplished safely.Mr. Bagley of the University of Michigan said there was a simpler solution to high drug prices than patchwork state importation programs: Having the U.S. government negotiate with drug companies over prices, just as many other nations, including Canada, do.“This whole thing is a jerry-rigged, complicated approach to a problem that’s amenable to a pretty straightforward solution, which is that you empower the government to bargain over the price for drugs,” he said. “So instead, we’re sort of trying to exploit the machinery that Canada has created and that we were too timid to create.”