IntroductionCompulsive Sexual Behavior Disorder (CSBD) and problematic pornography use (PPU) frequently co-occur with substance use disorders, yet their associations with specific substances in non-clinical populations remain poorly understood. The present study examined associations between alcohol and cannabis use severity and CSBD and PPU symptoms in a non-clinical adult sample.MethodsEligible adults were invited to complete an anonymous online survey between May and October 2025. Alcohol and cannabis use severity scores were assessed using AUDIT and CUDIT-R questionnaires, respectively. Participants compulsive sexual behavior disorders (CSBD) and problematic pornography use (PPU) scores were assessed using CSBI-13 and BPS questionnaires. Associations between substance use severity and compulsive sexual behaviors were assessed using linear adjusted regression.ResultsA total of 158 adults (61.4% women) aged 18–60 years were analysed with a mean alcohol and cannabis use severity scores of 16.29 (± 4.53) and 15.49 (± 5.08), respectively among current users, and a mean compulsive sexual behavior disorders of 21.14 (± 7.74), with a mean PPU score of 6.99 (± 2.55). In unadjusted regression models, increases in alcohol and cannabis use severity were associated with increases in CSBD and PPU scores. However, no significant increase of both outcomes was observed for alcohol use severity (CSBD: B = 0.18, 95% CI [-0.13; 0.49], p = .251; PPU: B = 0.04, 95% CI [-0.05; 0.13], p = .381) and cannabis use severity (CSBD: B = 0.09, 95% CI [-0.13; 0.31], p = .409; PPU: B = 0.03, 95% CI [-0.03; 0.09], p = .325) after controlling for age and gender.ConclusionOur study showed a positive but non-significant association between alcohol and cannabis use severity with both CSBD and PPU after controlling for age and gender, suggesting the underlying associations may be explained by sociodemographic differences in the study population. However, longitudinal studies and advanced analysis approaches including those that handle zero inflated data or latent dependant variable are needed to validate these findings.
Strengthening evidence-based practices in assessment and treatment planning for substance use disorder: an evaluation of a Swedish training program for social services
Background and aimSocial workers regularly encounter clients affected by substance use disorders (SUD), yet training in evidence-based assessment and interventions remains limited. In Sweden, municipal social workers have statutory responsibility for SUD assessment, intervention planning and client follow-up which underscores the need for targeted professional education. This study aimed to: (i) describe social workers’ baseline self-assessed competence in evidence-based practices for SUD and its associations with demographic and professional characteristics, and; (ii) examine knowledge gains associated with completion of an evidence-based educational intervention.MethodsA non-randomized pre–post design included 173 municipal social workers recruited from 64 municipalities across five cohorts (2021–2023). Baseline self-assessed competence was analyzed using ordinal logistic regression, and knowledge gains were assessed using module-specific pre–post items with paired t-tests with Cohen’s d.ResultsBaseline competence was rated as low to moderate, with professional experience predicting higher perceived competence. Substantial baseline knowledge gaps were observed, particularly in evidence-based psychosocial interventions and use of digital technology in assessment and planning of treatment. Knowledge increased significantly across all modules after training completion (d = 0.26–1.41). The largest knowledge gains were for modules on use of technology in the assessment and treatment-planning, biopsychosocial interventions, research-informed use of the assessment tool Addiction Severity Index (ASI), and the professional role in assessment and care planning. Score variability decreased across several modules.ConclusionCompletion of an immersive, online, evidence-based training was associated with meaningful improvements in social workers’ knowledge related to substance use assessment, intervention planning, and use of technology. Although causal inference is limited by the non-randomized single-group pre–post design, the findings support the potential of scalable educational interventions to address competence gaps in substance use services even in organizations with high caseloads, workforce turnover, and limited training opportunities.
RFK Jr. presents $700 million in mental health funding, but experts say grants aren’t new
The Trump administration on Wednesday said it was announcing $700 million in “new funding” for mental health and addiction programs, with an emphasis on combating homelessness resulting from severe, untreated mental illness.
But behavioral health experts instantly cast doubt on the claim, identifying the $700 million not as new funding but as the long-awaited release of existing grants that Congress had previously authorized and that the federal government already planned to spend.
STAT+: DOJ’s swift win in OhioHealth case should have hospitals studying their contracts, experts say
Legal experts say the speed and decisiveness of the Department of Justice’s proposed antitrust settlement with OhioHealth should put other hospitals on notice.
The DOJ and Ohio attorney general’s proposed settlement announced Wednesday would require nonprofit OhioHealth to quit using certain contracting practices that the agencies say prevented health insurers from selling cheaper policies. The deal, which comes just four months after the agencies sued the Columbus-based system, will likely push other health systems to examine their own contracting practices.
“I would expect lawyers will get pretty busy looking at contracts with payers,” said Katie Keith, the director of Georgetown University’s Center for Health Policy and the Law.
<![CDATA[Check out new phase 2 dose-ranging study data evaluating alixorexton in patients with narcolepsy type 2. ]]>
Digital Platform to Provide Health Data Feedback for Neurorehabilitation Patients: User-Centered Development and Proof-of-Concept Usability Study
Background: An increasing amount of digital health data are being collected across rehabilitation settings, but their integration into routine clinical practice remains limited, despite its potential to motivate patients or inform clinical decision-making. Specifically, effective visualization and communication of assessment outcomes to both patients and health care practitioners (HCPs) represent a key gap in the neurorehabilitation practice. Objective: This study describes the development and evaluation of RehaLink (author ND, ETH Zürich), a proof-of-concept mobile app that delivers structured, interpretable feedback from conventional and technology-based assessments to neurorehabilitation patients and HCPs. Methods: The app was developed through a 3-step iterative co-design process involving 17 inpatients with multiple sclerosis and 15 HCPs from a single rehabilitation center. The app integrates a full battery of conventional assessments routinely conducted at the clinic, as well as digital health metrics from the Virtual Peg Insertion Test, a validated technology-based assessment of upper limb function, as a proof of concept for integrating technology-based assessment data into clinical workflows. Three structured feedback sessions were conducted, in which participants evaluated feedback types, visualization formats, and app usability using Likert-scale ratings, preference rankings, open-ended questions, and the System Usability Scale. Data were analyzed using descriptive statistics and directed content analysis. Results: Across all 3 sessions, progress bars and color-coded indicators were consistently preferred over text-heavy or abstract formats by both patients and HCPs. A persistent set of competing demands was observed, with participants requesting both visual simplicity and access to absolute values and normative comparisons. HCPs tended to underestimate patients’ preference for informative visualizations. The perceived value of structured feedback increased over the course of the study; patients’ median ratings rose from 4.0 to 5.0 and HCPs’ from 4.0 to 4.5 on a 5-point Likert scale. The resulting mobile app prototype demonstrated high usability, with patients achieving a mean System Usability Scale score of 93.6 (mean 6.4; best imaginable) and HCPs 80.9 (SD 8.1; good), according to established benchmarks. Conclusions: These findings demonstrate the feasibility and value of a co-designed digital feedback tool for neurorehabilitation. By combining conventional and technology-based assessment outcomes in an accessible, user-centered format, the app has the potential to enhance patient engagement, support clinical decision-making, and advance the implementation of value-based, personalized care.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/c7bcf5f0f9b2f37adf8c6780da2e2e4b" />
The Feasibility of an App-Based Worksite Health Promotion Program to Improve Mental Well-Being and Work-Related Vitality in University Hospital Workers: Process and Preliminary Effect Evaluation Study
Background: University hospital employees face role-specific stressors that can impair mental well-being and work-related vitality. While worksite health promotion programs show potential for improving mental well-being by targeting lifestyle behaviors, most target single professions or hospital subunits, and evidence for mental well-being and work-related vitality remains mixed. Mobile apps offer unique advantages for delivering such worksite health promotion programs hospital-wide. However, accessible interventions tailored to a diverse workforce are lacking. Objective: This study aimed to investigate the feasibility of an app-based worksite health promotion program (the Recharge360 program [The Recharge Company]) targeting multiple lifestyle behaviors, including a team-based competition element, for improving mental well-being and work-related vitality of hospital employees over a 5-month follow-up period by evaluating two objectives: (1) the implementation process of the program, and (2) the preliminary effects of the program on mental well-being and work-related vitality. Methods: We included 532 employees (mean age 43, SD 12 y; n=482, 91% women; n=480, 90% highly educated) from a university hospital in Amsterdam, the Netherlands. The study had a single-arm, longitudinal pretest-posttest design lasting 5 months, during which employees participated in the 5-day Recharge360 program (Recharge week) 3 times—in weeks 1, 9, and 17. At baseline (T0) and after each Recharge week (T1-T3), we assessed mental well-being, work ability, need for recovery, and task performance. The process was evaluated by assessing recruitment, attrition, and survey completion rates, and the degree of participation. Preliminary effects were evaluated by linear mixed model regression analyses to assess changes in mental well-being and work-related vitality between baseline and follow-up. Results: Recruitment appeared feasible, but attrition rates were high (up to 70% in the final Recharge week), and the degree of participation decreased over time. We showed statistically significant, albeit small, increases in well-being at T3 (unstandardized β coefficient=2.08, 95% CI 0.33-3.84), with progressively larger improvements in the analyses among those who started at least 1, 2, and all 3 Recharge weeks (unstandardized β coefficient=3.27, 95% CI 1.09-5.45). Results for work-related vitality were mixed. The need for recovery remained unchanged, task performance increased slightly at T3 (unstandardized β coefficient=0.16, 95% CI 0.07-0.24). Work ability showed a small, but statistically significant, decline across follow-up (unstandardized β coefficient=−0.46, 95% CI −0.64 to −0.29). Conclusions: This app-based worksite health promotion program might be feasible to implement in a university hospital setting and shows potential to slightly improve mental well-being, but primarily for a selective group of highly educated, health-conscious women. While these findings support further investigation in a randomized controlled trial in similar university hospital settings, they also highlight the need for more participatory study designs to improve the tailoring of program components and engagement of underrepresented groups, as well as for a supportive culture and population-based approaches at the organizational level.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/05362a750c53672d55df1ef541cf64a9" />
Have Microbubbles Burst Through the Barriers of Genetic Medicine Delivery?
After more than 20 years working on viral and nonviral delivery modalities, Kenneth Greenberg, PhD, thought he had seen it all in genetic medicine delivery—until he met Steve Feinstein, MD, and Michael Davidson, MD, in 2021. Feinstein, a clinical cardiologist, had been working with ultrasound and contrast ultrasound for decades.
“Steve was scratching his head in the 90s trying to better diagnose heart disease patients, wondering why there’s a contrast agent for every other imaging modality except ultrasound,” Greenberg told Inside Precision Medicine.
Feinstein’s solution was microbubbles. These tiny gas-filled spheres (1-10 μm) with lipid, protein, or polymer shells can safely circulate through capillaries and resonate in response to ultrasound waves when injected intravenously, improving blood flow and tissue perfusion visualization before being cleared by the lungs and liver.
It was Feinstein that got the FDA to approve the first two ultrasound contrast imaging agents. Beyond diagnostics, he found new uses for microbubbles. Certain acoustic conditions could allow them to deliver therapeutic payloads directly into tissues.
Together with Davidson, a lipidologist and preventive cardiology specialist, Feinstein formed a long-term research partnership in Chicago’s academic medical community that resulted in the founding of SonoGene in 2000 to translate and commercialize ultrasound-mediated gene delivery.
Though SonoGene never made a splash, Feinstein and Davidson were able to generate preclinical data, which Greenberg found “mindblowing.”
“It showed me that you could use ultrasound and nonviral DNA payloads to achieve delivery and gene expression,” said Greenberg. “This is in rodents, but it was enough to persuade me that if it worked in humans anywhere near as well as it does in rodents, it could completely change the landscape of gene delivery. I thought it was just such an elegant idea. These components have been available for years, and we can repurpose them in a creative way to accomplish things that you could never do with existing modalities.”
In 2022, Greenberg, Feinstein, and Davidson joined forces to launch SonoThera, backed by a $60.75 million Series A financing with the goal of developing a nonviral, ultrasound-mediated gene delivery platform capable of producing safe, targeted, redosable, and cost-effective genetic medicines.
Four years later, investors are reaffirming that vision. SonoThera closed an oversubscribed $125 million Series B financing to advance its lead programs to the clinic and develop its ultrasound-enabled delivery platform. The funding comes at a crucial time for genetic medicine, where delivery challenges continue to temper therapeutic innovation.
RIPPLE effect
The genetic medicine revolution has produced transformative therapies across rare diseases, oncology, and metabolic disorders. Yet despite the success of viral vectors such as adeno-associated virus (AAV) and nonviral systems such as lipid nanoparticles (LNPs), researchers continue to grapple with payload-size constraints, limited tissue targeting, inability to redose, manufacturing complexity, and immune-related toxicities.
For Kenneth Greenberg, PhD, those challenges create an opening for a fundamentally different delivery strategy. “The field and investors recognize that this is a big problem, and no one has yet been able to solve it,” he said. “Coming up from a very different angle, I think it is getting people excited that this could ever come.”
Rather than engineering new viral capsids or nanoparticle chemistries, SonoThera has built its platform around two technologies already widely used in medicine: ultrasound systems and microbubble contrast agents. The company’s innovation lies in combining them with naked DNA payloads and proprietary ultrasound waveforms, called RIPPLE, to drive gene transfer into tissues.
“Our strategy has been to use the existing infrastructure as much as possible and not to develop bespoke hardware or novel microbubbles,” Greenberg said. “We want this to be widely utilized and have great patient access and clinicians to be familiar with the systems and the components.”
Unlike AAVs or LNPs, SonoThera does not package DNA inside a carrier. Instead, naked DNA and microbubbles circulate independently in the bloodstream until ultrasound is applied to a target organ. “There are some common misconceptions about the mechanism,” Greenberg said. “The mechanism basically involves taking the genetic payload, which is naked DNA. It’s not encapsulated in anything.”
The ultrasound activates circulating microbubbles in a multi-step process. First, acoustic energy creates temporary gaps in the endothelial lining of blood vessels, allowing DNA to access target tissues. The microbubbles are then collapsed, creating transient pores in cell membranes that permit intracellular entry of the payload. Finally, ultrasound-driven modulation of the nuclear pore complex facilitates transport of DNA into the nucleus for transcription and protein production. “The ultrasound can basically do everything in one single profile,” Greenberg said. “We can modulate the waveform in ways to drive this mechanism of delivery. We don’t need receptors, endosomes, or anything like that, which gives the platform a huge advantage in versatility to target different organs.”
That receptor-independent mechanism may offer one of the platform’s biggest advantages. Existing delivery systems typically depend on receptor-mediated cellular uptake, which can activate innate immune pathways and restrict tissue tropism. According to Greenberg, microbubbles largely avoid those limitations. “It’s also key to how we avoid the immune system, the innate immune system’s response that typically gets triggered by viruses and LNPs,” Greenberg said.
Because microbubbles are micron-sized rather than nanosized, they never enter the cell and are destroyed extracellularly after ultrasound activation. The DNA itself enters cells independently. While naked DNA degrades relatively quickly in circulation, Greenberg said its half-life of roughly 30 to 60 minutes is sufficient because infusion and ultrasound delivery occur simultaneously.
In contrast, LNPs enter cells through endocytosis, carrying lipids and genetic cargo that can activate innate immune sensors such as cGAS-STING and TLR9. AAVs similarly rely on receptor-mediated uptake pathways that can provoke immune responses and limit redosing.
From sonoporation to clinical translation
The platform’s flexibility has become increasingly apparent as SonoThera expanded beyond its initial liver studies. The company subsequently evaluated delivery to kidney, skeletal muscle, heart, brain, and adipose tissue. “What we’ve found is that the delivery technology works in all organs in the body, as far as we can tell,” Greenberg said. The notable exception is the lung, where air attenuates ultrasound energy.
Perhaps most striking is the company’s work in the brain. The SonoThera platform can temporarily open the blood-brain barrier and deliver payloads using the same mechanism as other tissues. “A common misconception is that the bone can attenuate the ultrasound energy. But that’s not the case,” Greenberg said. “The frequencies are such that they can penetrate easily through the skull and get into the brain.”
If that capability translates clinically, it could represent a significant advantage over delivery technologies that remain largely confined to the liver or a limited set of tissues.
SonoThera’s initial pipeline targets diseases where current delivery systems struggle. In Duchenne muscular dystrophy (DMD), the full-length dystrophin gene is too large for AAV vectors. The company’s ADPKD program has a larger payload.
“The overarching strategy when we’ve approached indications is that it’s challenging to get access to large payloads that are prohibitively large for AAVs,” Greenberg said. “With our ADPKD program, the payloads are even larger. That’s about a 22 KB payload, while the DMD payload is about 13 kb.”
Redosing is also important. Many genetic diseases require long-term treatment, especially in children whose tissues grow. AAV therapies are rarely administered again due to immune responses, making therapeutic expression difficult. “There are indications where the disease really requires redosing over time,” Greenberg said. “DMD is a good example because we’re treating really young boys as their bodies grow.”
SonoThera delivers mutation-agnostic full-length dystrophin with redoseability. The company also targets skeletal muscle, heart, and diaphragm simultaneously to address cardiopulmonary complications that kill many DMD patients.
The platform uses episomal DNA rather than genome editing. Greenberg believes the DNA behaves like AAV-delivered episomes, becoming chromatinized in the nucleus and maintaining expression. “We’ve got durability data out to a year so far with a single treatment,” he said.
Target tissue will determine redosing frequency: rapidly dividing cells may dilute episomal DNA, but quiescent tissues may maintain expression longer. Despite its focus on gene replacement, SonoThera has shown compatibility with gene editing and targeted integration methods. “For us, it’s really about using the right tool for the right job,” Greenberg said. “We don’t want to do gene editing just because it’s sexy.”
The scientific foundation for SonoThera’s platform is rooted in sonoporation, a concept that has been explored academically for decades but has never successfully reached the clinic. Greenberg believes the field historically struggled with two major hurdles: achieving sufficient transfection efficiency and broad biodistribution. “In the first two years of the company, we basically focused on solving those problems and really innovating to achieve extremely high delivery efficiency and broad organ biodistribution,” he said.
Those advances have now positioned the company to enter clinical development. SonoThera is conducting IND-enabling studies, manufacturing activities, and GLP toxicology work while refining clinical trial designs with physician and disease-area experts. The initial studies will focus primarily on safety while also evaluating biomarkers and early signs of efficacy. In DMD, the company has already generated preclinical biopsies showing expression of full-length dystrophin protein in muscle tissue.
Although SonoThera’s internal pipeline currently focuses on rare diseases, Greenberg sees broader opportunities ahead. Pharmaceutical companies have increasingly shifted attention toward common diseases with larger commercial potential, and many are searching for delivery platforms that can overcome the limitations of AAV-based therapies.
Investor confidence—but can it scale?
Greenberg says industry interest in nonviral, redosable systems may be better for common diseases, especially when manufacturing costs and reimbursement issues make one-time treatments unsustainable. SonoThera will advance its pipeline and partner with larger companies seeking platform access to capitalize on those opportunities. “Our strategy as a small biotech company has been to have our internal pipeline but, in parallel, be able to have licensing deals and partnerships that allow us to expand the reach of the technology and the much larger patient populations.”
The oversubscribed $125 million Series B financing suggests investors increasingly view delivery as the next major frontier in genetic medicine. As SonoThera approaches the clinic, it faces many of the same questions every new gene-delivery platform has faced for creating a paradigm-shifting delivery modality: safety, durability, and scale.
Because SonoThera’s platform relies on ultrasound-driven physical mechanisms rather than biological targeting, factors such as organ size, anatomy, blood flow, and patient variability could provide challenges to translatability.
Delivering DNA to a mouse liver or muscle is very different from delivering therapeutic amounts of genetic cargo throughout the muscles, heart, and diaphragm of a growing child with Duchenne muscular dystrophy. While microbubbles have a decades-long track record as imaging agents, repeated therapeutic delivery tools are a different proposition.
While the company argues that naked DNA and ultrasound avoid many of AAV’s payload limitations, questions remain about the doses required for large organs and whether manufacturing and administration can scale efficiently. Relatedly, SonoThera has reported preclinical expression lasting up to a year after a single treatment, but long-term persistence remains unknown. If repeat dosing is required, the company will need to demonstrate that repeated ultrasound exposure and cycles of vascular permeabilization can be performed safely over time.
SonoThera’s appeal reflects a broader reality: despite decades of innovation, delivery remains genetic medicine’s biggest unsolved problem. The company’s platform is scientifically elegant and potentially transformative, but only clinical data will determine whether ultrasound-mediated gene transfer represents a true breakthrough—or simply the latest attempt to solve one of biotechnology’s most stubborn challenges.
The post Have Microbubbles Burst Through the Barriers of Genetic Medicine Delivery? appeared first on Inside Precision Medicine.
Personalized Cartilage Graft Developed for Life-Threatening Infant Airway Narrowing
A study led by researchers at Children’s Hospital of Philadelphia (CHOP) demonstrated a new method of using decellularized cartilage with patient-specific cells to help enlarge the pediatric airways narrowed as a result of severe subglottic stenosis (SGS). The condition is a narrowing of the airway below the vocal cords and above the trachea, and affects an estimated 20,000 infants per year.
Researchers demonstrated in a preclinical model that this new method of airway reconstruction was faster, more effective, and able to overcome issues, such as donor site morbidity, insufficient tissue volume and delayed timeline, associated with the current standard grafts used for laryngotracheal reconstruction (LTR).
Riccardo Gottardi, PhD, assistant professor with the Perelman School of Medicine at the University of Pennsylvania and leader of the Bioengineering and Biomaterials (Bio2) lab, and Ian Jacobs, MD, medical director of the Center for Pediatric Airway Disorders in the Division of Otolaryngology (ENT) at CHOP, co-led the research, which is reported in Nature Communications, in a paper titled “A translational approach to airway reconstruction leveraging decellularized meniscus and cartilage progenitor cells.” In their paper the team said, “This technology has the potential to revolutionize the field of pediatric LTR.”
Severe subglottic stenosis (SGS) develops in children almost exclusively as a response to intubation, and affects nearly 1.5% of the over 200,000 infants in intensive care units each year in the United States, the authors explained. The most severe cases require laryngotracheal reconstruction (LTR), an open airway surgery that is used to enlarge the airway by implanting cartilage taken from a rib cage. While LTR is used to successfully treat thousands of children with subglottic stenosis, in many cases, young children often lack enough costal cartilage—the cartilage connecting our ribs to the sternum—for these grafts.
As a result, operations often need to be delayed, leaving the child attached to a tracheostomy tube until they are older and grown enough to supply sufficiently sized cartilage for an effective LTR, and there is a higher risk of needing follow-up surgery because the airway is at risk of narrowing again. “In adults, LTR has a 90% success rate with low rates of revision,” the team stated. “However, in children, success rates significantly drop, and the incidence of restenosis requiring revision surgery increases to over 24%.”
To improve this process and reduce the risk of these potential complications, Gottardi and Jacobs and colleagues have been looking at tissue engineering a laryngotracheal graft. Tissue engineering, the team wrote, could provide “an ideal alternative to autologous cartilage grafts to alleviate unnecessary comorbidities as well as reduce surgical time.” However, the complexity of the trachea prevents the use of conventional cartilage engineering techniques for this procedure.
“We needed something that could be equivalent to a piece of cartilage, integrate well with the surrounding tissue, be well tolerated by the patient, behave like native tissues and regrow and be part of the airway,” Gottardi said. “This required quite a bit of creative thinking because of the additional challenges in children who are so small and still growing.”
To overcome the limitations of existing methods, the researchers, led by former Gottardi lab member Paul Gehret, PhD, created a first-of-its-kind scaffold based on porcine meniscal cartilage decellularization (MEND – MENiscus Decellularization). They realized that if the cells, elastin, and blood vessels present in the meniscus are “digested” away, the meniscal cartilage becomes amenable to recellularization and integration while being less likely to provoke an immune response. In their paper the researchers explained, “Building on the strengths of previous decellularized therapies, we established an innovative approach that leverages the selective enzymatic removal of the elastin fibers and blood vessels uniquely present in the fibro-elastic cartilage of the meniscus to create microchannels, which support cellular invasion while substantially preserving native structure.”
Using ear-derived cartilage progenitor cells (eCPCs), which can mature into cartilage-producing chondrocytes, the researchers demonstrated that MEND can be recellularized after the removal of elastin and blood vessels and suitable for implantation in less than a month. “Notably, porcine menisci, such as those used in this study, are a highly abundant cartilage source, being easily available as a waste product of the food industry, which can ensure no shortage of material for surgeons to shape into an ideal implant,” the team noted.
Importantly, the new method needed to work in a clinically relevant timeframe. In a real-world scenario, clinicians may only have one or two months to be able to perform the procedure when it can still benefit the patient. Harvesting seed cells within days and creating a scaffold within three to four weeks is significantly less time than the six months that was typically needed for engineered cartilage. “Here we demonstrate that MEND can be fully recellularized in three days with ear-derived cartilage progenitor cells and reaches structural and functional maturation suitable for implant within three weeks of chondrogenic differentiation, a time frame compatible with clinical translation,” the authors stated.
They validated their technology in a preclinical rabbit in vivo model, and demonstrated better performance than costal cartilage, the standard of care, with no instances of adverse events reported. “Our results demonstrate airway expansion, graft reepithelialization, neocartilage formation, and integration with adjacent native laryngotracheal cartilage at three months,” the team stated. “Notably, MEND implants perform better in all outcomes than autologous costal cartilage, the standard of care.”
These findings will be further validated prior to proposing the procedure for patients suffering from severe subglottic stenosis. “These results demonstrate the feasibility of our translational tissue engineering approach to laryngotracheal reconstruction and could overcome the autograft-associated limitations in pediatric patients, decreasing the need for invasive revision surgery,” the investigators concluded.
“This research shows really promising data that suggests this novel approach could overcome the autograft-associated limitations we sometimes encounter when attempting laryngotracheal reconstruction in infants,” Jacobs said. “With more research, we expect this could decrease the need for invasive surgery, and we may be able to apply the technology to other conditions that require a cartilage graft.”
The post Personalized Cartilage Graft Developed for Life-Threatening Infant Airway Narrowing appeared first on GEN – Genetic Engineering and Biotechnology News.
OLE Identified as a Potential Alzheimer’s Therapy Targeting Microglia
A research collaboration between investigators from the Spanish National Research Council (CSIC), the Miguel Hernández University of Elche (UMH), and the École Polytechnique Fédérale de Lausanne (EPFL) has identified a molecule that may could be a new approach to treating Alzheimer’s disease (AD) by restoring the protective functions of microglia, immune cells found in the brain. The findings, published in Cell Death & Disease, said the molecule N-oleoyl-Leucine (OLE), which is derived from the Alzheimer’s disease-associated gene PM20D1, was shown to reduce amyloid pathology, improve cognition, and promote neuroprotection.
“One of the most significant findings is that we have identified a molecule capable of restoring microglia’s protective function,” said senior author José Vicente Sánchez Mut, PhD, principal investigator at the Functional Epi-Genomics of Aging and Alzheimer’s Disease laboratory at the Institute for Neurosciences, a joint CSIC-UMH center. “In Alzheimer’s disease, these cells become progressively impaired. Our results suggest that this process can be reversed, pointing to new therapeutic and research avenues to counteract the disease.”
In recent years, there has been a surge of research into microglia’s role in AD. As the researchers noted, genetic risk variants associated with AD are enriched in regions that regulate microglial function, and microglial gene-expression programs have been shown to be altered during disease progression. As the disease advances, microglia proliferate and accumulate around amyloid plaques, but lose their ability to maintain tissue homeostasis and clear amyloid beta (Aβ). At the same time these immune cells take on inflammatory and neurotoxic characteristics.
PM20D1 has been identified recently as a risk gene in the development of AD. It is a quantitative trait locus associated not only with Alzheimer’s disease but also with diabetes, obesity, and other disorders. People exhibiting lower PM20D1 expression have a higher risk of developing metabolic disorders and Alzheimer’s disease. Other prior research studies also showed that PM20D1 overexpression in mouse models reduced amyloid levels and cognitive deficits, making it a potentially fruitful area for additional study.
PM20D1 encodes a secreted enzyme that regulates the conjugation of fatty acids with amino acids, generating compounds known as N-acyl amino acids (NAAA). OLE is one of these amino acids and was selected for further investigation because PM20D1 activity in living organisms appears to favor its production and because OLE levels are strongly correlated with PM20D1 expression in both humans and mice.
“There is increasing evidence of microglia participation in Alzheimer’s disease (AD), which incentives their modulation to intercept the disease,” the researchers wrote. “Here, we describe a new mechanism by which the recently AD-associated Peptidase M20 Domain Containing 1 (PM20D1) instructs microglia to tackle AD.”
To evaluate OLE’s therapeutic potential, the team first tested it in genetically engineered Caenorhabditis elegans worms that produce beta-amyloid, where they showed that OLE treatment reduced protein aggregation and improved mobility. The researchers then administered OLE to APP/PS1 mouse models of AD for three months. Again, the mice demonstrated better performance in memory tests and showed reductions in amyloid plaque burden.
A cellular analyses found that microglia were the cells most responsive to OLE treatment.
“Single-cell analysis allowed us to determine that microglia were the cells that responded most strongly to the treatment,” said first author Victoria Pozzi, PhD, a postdoctoral researcher working in the Sánchez Mut lab. “From there, we observed that the compound helped these cells move toward beta-amyloid plaques and better contain the damage associated with the disease.”
The study also found that OLE increased Aβ chemotaxis and clearance in cultured microglia. In neuronal cultures exposed to Alzheimer’s-related stressors, OLE enhanced cell survival, indicating that the molecule may have direct neuroprotective effects in addition to its effects on immune cells.
The team believes OLE may function as a disease-modifying therapy by altering microglial behavior and reducing amyloid-associated damage, but because OLE was administered systemically in their experiments, more work is needed to determine whether its primary effects occur in microglia or whether it acts independently on multiple cell types. They also plan to investigate whether other N-acyl amino acids have therapeutic potential and whether OLE can influence tau pathology and neurodegeneration.
The post OLE Identified as a Potential Alzheimer’s Therapy Targeting Microglia appeared first on Inside Precision Medicine.