Category: 8. Health

If the findings of their study are confirmed by other research centers, the biomarker could be the first specific and quantifiable indicator for confirming long COVID. Currently, clinicians confer a diagnosis of long COVID based upon a collection of symptoms that patients develop after SARS-CoV-2 infection.

“If a patient arrives in clinic and they relate the persistence of typical signs and symptoms of long COVID, 12 weeks or more after COVID -19 infection, I give them a presumptive diagnosis, but I don’t have any blood tests or biomarkers to confirm this diagnosis,” said William Stringer, M.D., a Lundquist Institute investigator and senior author on the study.

The study results, reported in the journal Infection, detail the detection of SARS-CoV-2 protein fragments within extracellular vesicles (EVs) — tiny, naturally occurring packages that help cells share proteins, metabolites, and other materials. The researchers collected and analyzed blood samples from 14 patients over 12 weeks of aerobic exercise training (56 samples in all) in a clinical trial led by Stringer in long COVID.

The researchers found 65 distinct protein fragments from SARS-CoV-2 inside the EVs. These fragments come from the virus’s Pp1ab protein, an RNA Replicase enzyme which is key to how the virus copies itself and makes other viral particles. This protein is found uniquely in SARS-CoV-2, and not in uninfected human cells, noted Asghar Abbasi, Ph.D., a Lundquist Institute investigator and first author of the study.

Significantly, the researchers found that these viral peptides were demonstrated in each subject, but not each blood draw, in the EVs of Long COVID patients and were not detected in a separate control group of pre-pandemic EV samples.

These findings add to growing evidence that suggests that SARS-CoV-2 may persist in certain body tissues long after the initial infection. Some groups hypothesize these lingering viral reservoirs could play a role in Long COVID. How the virus reaches tissues without its usual entry points — such as the brain — remains an open question, and may be related to EV particles.

“We thought that maybe if the virus is circulating or moving in the body, we should try to see if EVs are carrying those viral fragments,” Abbasi explained.

This idea became part of an ongoing clinical trial led by Drs. Abbasi and Stringer, which was already studying EVs to see if they are linked to changes in immune function related to exercise and post-exertional malaise, a common symptom in these patients.

“While promising, the molecular signal of the viral peptides within the study samples was observed to be subtle and not consistently detected at every blood collection time point,” said Patrick Pirrotte, Ph.D., associate professor at TGen, director of the Integrated Mass Spectrometry Shared Resource at TGen and City of Hope, and co-senior author of the study. “There’s still a lot to unpack that we don’t know at this point.”

For instance, he added, the researchers don’t know if the exercise itself drives the expression of viral programs intracellularly, and then those viral programs result in proteins that are going to be shed, or if there is a permanent reservoir in those cells, and it’s just a matter of detecting it at a certain time point. Although the identified peptides originated from one of the virus’ largest proteins, the researchers did not detect other comparably large proteins indicative of active viral replication. It’s possible that the peptides contained in the EVs are just molecular “trash” leftover after the formation of new viral proteins.

“We haven’t run [our tests] on people without long COVID symptoms who are currently, or who were, infected with COVID,” said Stringer. “This raises the question: is this just continuing to take out the trash from the COVID infected cell or is this really ongoing replication someplace? I think that’s the mechanistic issue that needs to be resolved in future studies.”

The Pulmonary Education and Research Foundation (PERF) and the UCLA David Geffen School of Medicine (DGSoM)-Ventura County Community Foundation (VCCF) funded this research.

A US medical journal has warned against using ChatGPT for health information after a man developed a rare condition following an interaction with the chatbot about removing table salt from his diet.

An article in the Annals of Internal Medicine reported a case in which a 60-year-old man developed bromism, also known as bromide toxicity, after consulting ChatGPT.

The article described bromism as a “well-recognised” syndrome in the early 20th century that was thought to have contributed to almost one in 10 psychiatric admissions at the time.

The patient told doctors that after reading about the negative effects of sodium chloride, or table salt, he consulted ChatGPT about eliminating chloride from his diet and started taking sodium bromide over a three-month period. This was despite reading that “chloride can be swapped with bromide, though likely for other purposes, such as cleaning”. Sodium bromide was used as a sedative in the early 20th century.

The article’s authors, from the University of Washington in Seattle, said the case highlighted “how the use of artificial intelligence can potentially contribute to the development of preventable adverse health outcomes”.

They added that because they could not access the patient’s ChatGPT conversation log, it was not possible to determine the advice the man had received.

Nonetheless, when the authors consulted ChatGPT themselves about what chloride could be replaced with, the response also included bromide, did not provide a specific health warning and did not ask why the authors were seeking such information – “as we presume a medical professional would do”, they wrote.

The authors warned that ChatGPT and other AI apps could ‘“generate scientific inaccuracies, lack the ability to critically discuss results, and ultimately fuel the spread of misinformation”.

ChatGPT’s developer, OpenAI, has been approached for comment.

The company announced an upgrade of the chatbot last week and claimed one of its biggest strengths was in health. It said ChatGPT – now powered by the GPT-5 model – would be better at answering health-related questions and would also be more proactive at “flagging potential concerns”, such as serious physical or mental illness. However, it stressed that the chatbot was not a replacement for professional help.

The journal’s article, which was published last week before the launch of GPT-5, said the patient appeared to have used an earlier version of ChatGPT.

While acknowledging that AI could be a bridge between scientists and the public, the article said the technology also carried the risk of promoting “decontextualised information” and that it was highly unlikely a medical professional would have suggested sodium bromide when a patient asked for a replacement for table salt.

As a result, the authors said, doctors would need to consider the use of AI when checking where patients obtained their information.

The authors said the bromism patient presented himself at a hospital and claimed his neighbour might be poisoning him. He also said he had multiple dietary restrictions. Despite being thirsty, he was noted as being paranoid about the water he was offered.

He tried to escape the hospital within 24 hours of being admitted and, after being sectioned, was treated for psychosis. Once the patient stabilised, he reported having several other symptoms that indicated bromism, such as facial acne, excessive thirst and insomnia.

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A new study conducted by the University of California, San Diego, unveiled that commonly prescribed anticholinergic drugs may increase the risks of mild cognitive impairment (MCI).

Cognitive impairment is an umbrella term used to describe the decline in an individual’s ability to think, learn, remember, reason and solve problems. 

MCI is a specific type of cognitive impairment characterized by a noticeable decline in a person’s thinking abilities. It is potentially considered as an early sign of dementia.

The study analyzed 688 older adults of an average age of 74 years no initial cognitive issues.

It was observed that those who took anticholinergic medications were 47% more likely to develop memory problems over a decade.

These medicines are prescribed for conditions such as high blood pressure, allergies, and depression.

The major findings of the study are:

• The participants with brain markers associated with Alzheimer’s were four times more vulnerable to cognitive decline after taking these drugs.
• Those having a genetic vulnerability to Alzheimer’s had 2.5 times higher odds of impairment.
• Medicines like blood pressure drugs (metoprolol, atenolol), allergy medications (loratadine), and antidepressants (bupropion) highly contribute to developing cognitive impairment.

These drugs typically inhibit the release of acetylcholine, a neurotransmitter critical for memory and learning.

While they are effective for their intended uses, long-term usage raises cognitive concerns.

To combat this, the study recommends exercising regularly, eating antioxidant-rich diets, and consuming certain fruits that may help to slow cognitive decline.

The study adds to growing evidence that some medications while being advantageous for one condition may inadvertently impact brain health highlighting the need for personalized medical care. 

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This study provides an up-to-date evaluation on the global, regional, and national burden of early-onset CVD attributable to PM_2.5 from 1990 to 2021. Males, individuals living in regions with lower SDI, and those with IHD experience a higher burden. Over the past three decades, there was a substantial decrease in early-onset CVD burden attributable to total and household PM_2.5, especially in regions with higher SDI. However, the corresponding burden from ambient PM_2.5 continued to rise and only began to decline since the last decade. In addition, the reduction in early-onset CVD burden was less prominent than that of late-onset CVD. Such findings underscore that even in the context of global population aging, the PM_2.5-related early-onset CVD burden remains a critical concern.

Most previous studies focused on the overall CVD burden attributable to PM_2.5, with few age-specific analyses and insufficient attention to younger populations [13, 15, 21]. Besides, there has been a decreasing trend in the all-age CVD death and DALY rates attributable to both ambient and household PM_2.5 exposure over the past three decades [9]. However, how the early-onset CVD burden varied across different regions and time periods remains unclear. Our study is the first to fill this gap by conducting a comprehensive analysis of early-onset CVD burden attributable to PM_2.5 from 1990 to 2021 at the global level. We also present the late-onset CVD burden and age-specific burden by 5-year intervals. The results show that the attributable burden was consistently higher in older age groups, suggesting their greater susceptibility. Interestingly, while the burden of both early- and late-onset CVD from total and household PM_2.5 has declined, the reduction in the early-onset burden is smaller compared to the late-onset burden. Additionally, in contrast to the decline in late-onset CVD burden, the early-onset CVD burden due to ambient PM_2.5 even increased slightly. This suggests a need for sustained attention to younger populations who may experience slower improvements despite lower absolute burden.

Our study reveals obvious sexual differences in the burden of early-onset CVD attributable to PM_2.5 pollution. In general, males experience a higher burden compared to females, which is consistent with higher PM_2.5-related CVD risk among males reported in previous researches [22,23,24]. This between-sex difference is more pronounced for ambient PM_2.5 pollution and less prominent for household PM_2.5. Several factors might contribute to this heterogeneity. First, there is generally a higher prevalence of traditional cardiovascular risk factors among males, such as hypertension, alcohol consumption, and smoking, which contributed to a higher overall CVD burden [9, 25, 26]. Second, social and occupational factors might also play an important role. Men are more likely to engage in outdoor labor-intensive work, leading to greater exposure to ambient air pollution. Conversely, women are more often exposed to indoor air pollution due to their involvement in household tasks such as cooking [27, 28]. These results underscore the importance of accounting for sex-specific exposure patterns when designing public health policies aimed at reducing PM_2.5-related disease burdens. Reducing ambient PM_2.5 exposure is particularly important for mitigating CVD burden among men, while minimizing both ambient and indoor exposure would be equally crucial for women.

Substantial variations by SDI were illustrated in the burden of early-onset CVD attributable to PM_2.5 pollution. Similar to patterns observed in studies on other non-communicable diseases [29], a reversed U-shaped association was found between SDI and the early-onset CVD burden attributable to ambient PM_2.5. In contrast, the corresponding burden due to household PM_2.5 showed a generally decreasing trend as SDI increased. Low-SDI regions in Sub-Saharan Africa and South Asia faced the highest burden from household PM_2.5, while middle-SDI regions in North Africa, the Middle East, South Asia, and East Asia experienced the greatest burden from ambient PM_2.5. This pattern could be explained by the regional economic and environmental differences. Specifically, low-SDI countries, largely dependent on solid fuels, have higher household PM_2.5 exposure, whereas middle-SDI countries face increased ambient pollution due to rapid urbanization and industrialization [30, 31]. High-SDI regions had the lowest burden from both ambient and household PM_2.5, which might be largely due to the use of cleaner energy, stricter environmental regulations, more resources of individual protective measures, and improved public health and clinical systems. These regional differences underscore the critical influence of socioeconomic development on the early-onset CVD burden attributable to PM_2.5 pollution.

To effectively mitigate the early-onset CVD burden due to PM_2.5 pollution, tailored air quality policies and interventions based on regional economic and environmental contexts are warranted. In low-SDI countries, international cooperation is essential, including technology transfer to promote clean cooking stoves, clean energy use, and improved household ventilation. Global financial support is also needed to subsidize infrastructure upgrades and clean energy transitions. For middle-SDI countries undergoing rapid industrialization and urbanization, stringent air quality management plans including tightening industrial emission standards, expanding public transportation systems, and promoting clean energy transitions are needed. High-SDI countries, while facing relatively lower PM_2.5 burdens, should continue strengthening environmental regulations, advancing control technologies, and investing in long-term pollutant management. They can also play a leading role in supporting global air pollution control efforts through research collaboration, funding, and cross-border policy communication.

The health effects and corresponding disease burden attributable to PM_2.5 may also vary depending on its chemical composition and sources, which differ substantially across regions [32]. Previous studies reported that carbonaceous components and PM_2.5 from fossil fuel combustion might pose higher cardiovascular risks [33,34,35,36], which could theoretically contribute to a higher disease burden. However, due to data limitations, our analysis focused on total PM_2.5 mass and did not account for the heterogeneity in chemical constituents and sources. This limitation may also contribute to uncertainties in regional burden estimates. Future studies integrating data on PM_2.5 chemical composition and source-specific toxicity are warranted to improve the precision of disease burden estimates and guide more targeted interventions.

Over the past three decades, there has been a significant decrease in the early-onset CVD burden attributable to total and household PM_2.5 pollution, especially in regions with higher SDI levels. In contrast, the burden from ambient PM_2.5 slightly increased at the global level, which was mainly driven by increasing burden in less-developed regions [31]. Since the year 2012, early-onset CVD burden from ambient PM_2.5 has exceeded that from household PM_2.5, and became the primary contributor to PM_2.5-related burden. This shift illustrates the effectiveness of the global efforts in promoting cleaner energy sources including natural gas and electricity for household use, and emphasizes that stricter actions especially on ambient PM_2.5 pollution are needed to reduce CVD burden in the future.

This study provides a comprehensive and up-to-date evaluation on the global, regional, and national distributions and temporal trends of early-onset CVD burden from PM_2.5 exposure. Our findings offer scientific guidance for multiple fields, including public health, clinical practice, and environmental health policy, in developing targeted interventions and management strategies to promote global cardiovascular health.

There are several limitations that should be acknowledged. First, PM_2.5 is a complex mixture comprising multiple constituents, each with distinct physicochemical properties [37]. The composition of PM_2.5 can vary significantly by source, season, and region [38, 39]. However, the GBD 2021 study assumes spatial homogeneity in PM_2.5 composition, potentially leading to inaccurate estimations in specific locations [29]. Future studies should take the heterogeneity of PM_2.5 composition and source into consideration when evaluating the disease burden attributable to PM_2.5. Second, our assessment of household PM_2.5 pollution did not account for solid fuel use for heating, which is also an important contributor to indoor air pollution and a known risk factor for CVD [9, 40]. Thus, future studies should explore the contribution of solid fuel use for heating to the disease burden attributable to household PM_2.5 pollution. Third, the effect estimates in this study rely on available epidemiological datasets, which might be limited in many low- and middle-income regions. Issues such as underdiagnosis and inadequate health care access could lead to biases in the estimation. Fourth, the current GBD 2021 dataset only evaluates burden of IHD as an aggregated category. Therefore, we were unable to estimate the disease burden by finer subtypes of IHD such as acute myocardial infarction, angina, or chronic IHD separately. In addition, most existing cohort studies on air pollution have focused on overall IHD rather than its specific subtypes, leading to insufficient evidence supporting more detailed burden estimation. Therefore, future studies with finer disease categories are warranted and would be valuable to inform targeted interventions. Last, while the relative risk estimates used in GBD 2021 were derived from epidemiological studies that adjusted for major confounders, residual confounding from unmeasured factors may still exist. In addition, potential interactions and mediation among different risk factors are not fully captured in these models. Future studies incorporating more detailed covariate data and advanced analytical methods are needed to better account for residual confounding and to explore these complex relationships.

Introduction

Metal allergies can cause inflammatory conditions affecting the skin and mucous membranes, often complicating diagnoses when associated with dental prostheses. Differentiating between allergic reactions to dental metals and other inflammatory lesions, such as oral lichen planus, can be difficult in the oral cavity. Oral lichen planus is a chronic inflammatory condition with multiple possible etiologies, including autoimmune responses, infections, medications, and, in some cases, metal allergies.

Previous studies have reported an association between dental metal restorations and oral lichen planus, leading to the recommendation of metal removal as a treatment option.¹ However, the persistence of symptoms following metal removal suggests that other pathologies, such as oral lichen planus, may play a more significant role.² This case report presents a patient with persistent oral lesions initially attributed to metal allergies, where treatment targeting the suspected allergy was unsuccessful, ultimately revealing oral lichen planus as the primary diagnosis.

Patients and Methods

Patient Information

A 55-year-old female patient presented with redness and pain in the buccal gingiva near the right mandibular first molar (#46). Her medical history included atrophic gastritis, and she had a known metal allergy. The patient had no previous history of oral lichen planus. The patient’s family history was unremarkable.

Present Illness

The patient was referred to our department from a dermatology clinic specializing in allergies and presented with symptoms suggestive of a metal allergy, including redness and lace-like white patches on the buccal gingiva adjacent to tooth #46. Redness and lace-like white patches were observed on the buccal gingiva near tooth #46, accompanied by pain and inflammation (Figure 1).

Figure 1 Redness and lace-like white patches on the buccal gingiva near tooth #46, with associated pain and inflammation.

Clinical Findings

Upon intraoral examination, full-cast crowns were identified on teeth #16, #17, #26, #27, #36, #37, #46, and #47, whereas partial-cast crowns were found on teeth #24, #25, #34, and #35 using the FDI two-digit tooth numbering system.³ Tooth #45 was restored with a composite resin, and the remaining teeth were natural (Figure 2). No extra-oral abnormalities were observed.

Figure 2 Full cast crowns on teeth #16, #17, #26, #27, #36, #37, #46, and #47, and partial cast crowns on teeth #24, #25, #34, and #35. Composite resin restoration on tooth #45.

Intraoral Metal Element Analysis

Samples were collected from all intraoral restorations using a silicone point (M3-28, Shofu, Kyoto) and analyzed using an X-ray fluorescence spectrometer (MESA-500W, HORIBA, Kyoto). The analysis detected the presence of Zn and Co in full-cast crowns on teeth #16, #17, #26, #27, #36, #37, #46, and #47, as well as in partially-cast crowns on teeth #24, #25, and #34 (Table 1).

Table 1 Intraoral Metal Element Analysis of Dental Crowns

Diagnosis and Treatment

Based on the intraoral metal element analysis, a diagnosis of metal allergy was confirmed.⁴ In September 2021, the metal crowns were removed and replaced with provisional restorations made of autopolymerizing resin. During the crown removal, suction, gauze, and an extraoral vacuum were employed to prevent exposure to metal fragments. No acute symptoms were observed postoperatively. Full-zirconia ceramic crowns were placed in December 2021. However, redness and pain persisted even eight months after crown placement (Figure 3).

Figure 3 Persistent redness and pain in the buccal mucosa eight months after zirconia crowns were placed on teeth #46.

Subsequently, in August 2022, the metal crown of the right mandibular second molar (#47) was removed and replaced with a full zirconia ceramic crown, similar to the approach used for tooth #46 (Figure 4). Despite these interventions, the symptoms did not subside, prompting reconsideration of the initial diagnosis. The patient was referred to the Department of Oral and Maxillofacial Surgery.

Figure 4 White patches remained on the oral mucosa after the healing of oral lichen planus.

Further Diagnostic Evaluation and Outcome

In November 2022, a punch biopsy was performed, which confirmed a diagnosis of oral lichen planus through histopathological analysis. Subsequently, the oral surgeon initiated steroid therapy, including dexamethasone 0.1% oral ointment and azunol 4% mouthwash. Regular follow-up (monthly) showed gradual resolution of the mucosal inflammation, and by March 2023, the oral lichen planus had fully healed (Figure 5). The patient was continuously monitored for recurrence.

Figure 5 Oral cavity overview after the healing of oral lichen planus.

Results

This case represents an unusual presentation of oral lichen planus that was initially diagnosed as a metal allergy-induced lesion. The removal of dental metals and their replacement with zirconia crowns did not lead to symptom improvement, suggesting that metal allergy was not the sole cause of the patient’s symptoms. Successful resolution following steroid therapy supports the hypothesis that oral lichen planus rather than metal allergy is the primary pathology.

Discussion

Dental metal allergies can manifest in various ways, and management approaches should take into account factors such as mucocutaneous symptoms, the involvement of allergy-positive metals, and individual patient response to the removal of dental metals.⁵ In this case, despite the detection of allergy-positive metals (Zn and Co), mucosal inflammation persisted following metal removal. This finding underscores the need for a comprehensive approach to diagnosing oral lesions, particularly in patients with complex presentations.⁶ Differential diagnoses considered included lichenoid contact reaction, systemic lupus erythematosus, and mucous membrane pemphigoid. These were ruled out based on clinical presentation and histopathological features. Oral lichen planus has been linked to various etiologies beyond metal allergies, including bacterial and viral infections, medications, stress, and autoimmune diseases.⁷ In cases where metal allergy is suspected, but symptoms persist despite the allergen removal, other potential causes, such as oral lichen planus, must be carefully evaluated. In this case, the efficacy of steroid therapy highlights the importance of considering alternative treatments, including immunosuppressants, antiviral medications, and biologics, especially in patients who do not respond to conventional therapies.⁸

Chronic oral lichen planus can severely impact a patient’s quality of life due to persistent pain and discomfort.⁹ Therefore, treatment goals should not only focus on symptom relief and recurrence prevention but also on improving the patient’s overall quality of life. Patient education and regular follow-ups are essential components of long-term management.¹⁰

Conclusion

This case highlights the need for a multidisciplinary approach to manage oral inflammatory conditions. Prosthodontists and dental practitioners should consider various perspectives and collaborate with other departments when facing persistent oral lesions, particularly when treatments targeting suspected metal allergies fail to yield positive results and desired outcomes. Alternative diagnoses, such as oral lichen planus, should be considered, and appropriate interventions should be implemented to achieve optimal patient care.

Acknowledgments

We would like to express our gratitude to Dr. Kitagawa from the Center of Oral Clinical Examination and Dr. Taguchi from the Department of Oral and Maxillofacial Surgery for their dedicated efforts in managing this condition.

Additionally, the patient provided written informed consent for the publication of this case report, including the use of clinical images. Ethical approval was not required for this case report, as no identifiable personal information is disclosed, and institutional guidelines at Hiroshima University Hospital do not require IRB review for single case reports.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

References

1. Sugiyama M, Kawashima A, Ishida K, et al. Clinical features of oral lichen planus related to dental metal restorations. Oral Sci Int. 2012;9(2):81–85.

2. Kato T, Matsuda S, Ishikawa J, et al. Refractory oral lichen planus after dental metal replacement: a retrospective study. J Dermatol. 2020;47(5):506–512.

3. FDI World Dental Federation. FDI two-digit tooth numbering system. Int Dent J. 1971;21(1):104–106.

4. Sakanashi EN, Kikuchi K, Matsumura M, et al. Chapter 7-Allergic contact dermatitis to dental alloys: evaluation, diagnosis and treatment in Japan — reflectance confocal laser microscopy, an emerging method to evaluate allergic contact dermatitis. In: Confocal Laser Microscopy – Principles and Applications in Medicine, Biology, and the Food Sciences. 2013.

5. Akiba Y, Watanabe M, Mine A, et al. With the aim of treatment guideline development for dental metal allergy and related diseases. Ann Jpn Prosthodont Soc. 2016;8(4):327–339. doi:10.2186/ajps.8.327

6. Stone SJ, McCracken GI, Heasman PA, et al. Cost-effectiveness of personalized plaque control for managing the gingival manifestations of oral lichen planus: a randomized controlled study. J Clin Periodontol. 2013;40:859–867. doi:10.1111/jcpe.12126

7. Louisy A, Humbert E, Samimi M. Oral lichen planus: an update on diagnosis and management. Am J Clin Dermatol. 2024;25:35–53. doi:10.1007/s40257-023-00814-3

8. Rotaru D, Chisnoiu R, Picos AM, et al. Treatment trends in oral lichen planus and oral lichenoid lesions (Review). Exp Ther Med. 2020;20:198. doi:10.3892/etm.2020.9328

9. Salgado DS, Jeremias F, Capela MV, et al. Plaque control improves the painful symptoms of oral lichen planus gingival lesions. A short-term study. J Oral Pathol Med. 2013;42:728–732. doi:10.1111/jop.12093

10. Hashemipour MA, Sheikhhoseini S, Afshari Z, et al. The relationship between clinical symptoms of oral lichen planus and quality of life related to oral health. BMC Oral Health. 2024;24:556. doi:10.1186/s12903-024-04326-2

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• At extended median follow-up of 19.7 months, median overall survival (“OS”) increased from 16.33 to 28.94 months
• Clinical efficacy correlated with the magnitude of T cell responses specific to mutant-KRAS (“mKRAS”) induced by ELI-002
• 77% reduction in the risk of death and 88% reduction in the risk of relapse, associated with T cell responses above the threshold for anti-tumor efficacy
• ELI-002 induced both CD4+ and CD8+ mKRAS-specific T cell responses in most patients, and evidence of antigen-spreading to patient-specific neoantigens not included in ELI-002 was observed
• Final event-driven disease-free survival (“DFS”) analysis for the randomized Phase 2 AMPLIFY-7P study evaluating ELI-002 7P monotherapy in pancreatic ductal adenocarcinoma (“PDAC”) is anticipated in Q4 2025

BOSTON, Aug. 12, 2025 (GLOBE NEWSWIRE) — Elicio Therapeutics, Inc. (Nasdaq: ELTX, “Elicio” or the “Company”), a clinical-stage biotechnology company developing a pipeline of novel immunotherapies for the treatment of cancer, today announced the publication of follow-up data from the Phase 1 AMPLIFY-201 study evaluating ELI-002 in the peer-reviewed scientific journal, Nature Medicine. The article, entitled, “Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: Phase 1 AMPLIFY-201 trial final results,” highlights that with extended follow-up, more than two-thirds of participants (17 of 25) whose T cell responses exceeded the antitumor efficacy threshold experienced a significantly reduced risk for relapse or death.

“This publication, combined with the early promising clinical data we’ve generated to date, further strengthens our belief that our Amphiphile (“AMP”) platform represents a potentially transformative approach in the treatment of mKRAS-driven tumors,” commented Robert Connelly, Chief Executive Officer of Elicio.

Chris Haqq, MD, Ph.D., Chief Medical Officer of Elicio, added, “The updated Phase 1 AMPLIFY-201 data further demonstrate that the AMP platform has the potential to provide durable benefit to PDAC patients in the adjuvant setting. These promising results together with the recent positive recommendation from the Independent Data Monitoring Committee that the randomized ongoing Phase 2 AMPLIFY-7P study should continue without modification to final DFS analysis, represent critical advancements for our promising lead program.”

Key Findings:

• 25 adjuvant-stage patients with solid tumors (20 PDAC, 5 colorectal) were enrolled for treatment based on positive for minimal residual mKRAS disease after locoregional treatment, with data reported through September 24, 2024.
• Direct ex vivo mKRAS-specific T cell responses were observed in 21/25 patients (84%), including both CD4+ and CD8+ T cell responses in 71% of patients, and 6/6 patients (100%) treated at the recommended Phase 2 dose (“RPD2”); the induction of both CD4+ and CD8+ T cells correlated with overall tumor biomarker response (p<0.0035).
• Tumor biomarker responses were observed in 21/25 patients (84%), with complete biomarker clearance observed in 6/25 patients, as determined by tumor-informed circulating tumor DNA analysis (24%; 3 PDAC, 3 colorectal).
• At 19.7 months median follow-up (compared to 8.5 months previously), the median relapse-free survival (“RFS”) was 16.33 months, and the median OS was 28.94 months for the 25-patient cohort.
• Efficacy correlated with ELI-002-induced mKRAS-specific T cell response (≥ versus < threshold: 9.17-fold over baseline; threshold defined through receiver-operating curve analysis):
  • Median tumor biomarker reduction was 55.2% compared to 36.7% in above versus below threshold T cell responders, respectively (p<0.0024).
  • 11/17 patients with T cell response above threshold remained free from radiographic progression while 8/8 patients with below threshold T cell responses had confirm radiographic progression (7/8 had died); Relative Risk of Progression or Death in below threshold T cell responders was 2.96.
  • Median RFS was not reached compared to 3.02 months in above versus below threshold T cell responders, respectively (HR 0.12, 95% CI 0.02 to 0.62, p=0.0002); patients with greater than threshold T cell response had an 88% reduction in the risk of progression or death.
  • Median OS was not reached compared to 15.98 months in above versus below threshold T cell responders, respectively (HR 0.23, 95% CI 0.06 to 0.85, p=0.0099); patients with greater than threshold T cell response had an 77% reduction in the risk of death.
• Antigen-spreading, a process where the immune system, initially targeting the mKRAS antigens in ELI-002, expands its response to recognize additional antigens in the patient’s tumor leading to a broader and more effective anti-tumor response, was observed in 67% of patients, with increased T cells reactive to personalized, tumor neoantigens absent from ELI-002; overall, increased T cell responses were observed in 13/52 (25%) of evaluated tumor neoantigens.
• ELI-002 was well tolerated, with no safety concerns identified, and no dose-limiting toxicities or ≥ Grade 3 treatment-related adverse events were observed.

	Pant, et al. Nature Medicine. 2024	Wainberg, et al. Nature Medicine. 2025
DCO	6 Sept 2023	24 Sept 2024
Median Follow-up	8.5 months	19.7 months
Median RFS (n=25)	16.33 months	16.33 months
Median OS (n=25)	16.33 months	28.94 months
mKRAS T Cell Response Threshold	12.75x (median)	9.17x (ROC-defined)
Patients ≥ mKRAS T Cell Response Threshold	13/25	17/25
mKRAS T Cell Response Correlation to:
Tumor Biomarker Response	P=0.0014	P=0.0024
RFS	HR 0.14, P=0.0167	HR 0.12, P=0.0002
OS	NR	HR 0.23, P=0.0099

DCO: Data cut-off; RFS: Relapse-free survival; OS: Overall survival; ROC: Receiver-operating curve; NR: Not reported

Elicio Therapeutics, Inc. (Nasdaq: ELTX) is a clinical-stage biotechnology company advancing novel immunotherapies for the treatment of high-prevalence cancers, including mKRAS-positive pancreatic and colorectal cancers. Elicio intends to build on recent clinical successes in the personalized cancer vaccine space to develop effective, off-the-shelf vaccines. Elicio’s Amphiphile (“AMP”) technology aims to enhance the education, activation and amplification of cancer-specific T cells relative to conventional vaccination strategies, with the goal of promoting durable cancer immunosurveillance in patients. Elicio’s ELI-002 lead program is an off-the-shelf vaccine candidate targeting the most common KRAS mutations, which drive approximately 25% of all solid tumors. Off-the-shelf vaccine approaches have the potential benefits of low cost, rapid commercial scale manufacturing, and rapid availability of drug to patients especially in neo-adjuvant settings and for prophylaxis in high-risk patients, contrary to personalized vaccines approaches. ELI-002 is being studied in an ongoing, randomized clinical trial in patients with mKRAS-positive pancreatic cancer who completed standard therapy but remain at high risk of relapse. ELI-002 also has been studied in patients with mKRAS-positive colorectal cancer (“CRC”) in Phase 1 studies. The updated AMPLIFY-201 Phase 1 data for PDAC and CRC was presented at the ESMO Immuno-Oncology Congress 2024 and included a 16.3-month median recurrence-free survival and 28.9-month median overall survival for the full study population. In the future, Elicio plans to expand ELI-002 to other indications including mKRAS positive lung cancer and other mKRAS positive cancers. Elicio’s pipeline includes additional off-the-shelf therapeutic cancer vaccines candidates, including ELI-007 and ELI-008, that target BRAF-driven cancers and p53 hotspot mutations, respectively. For more information, please visit www.elicio.com.

About ELI-002

Elicio’s lead product candidate, ELI-002, is a structurally novel investigational AMP cancer vaccine that targets cancers that are driven by mutations in the KRAS-gene—a prevalent driver of many human cancers. ELI-002 is comprised of two powerful components that are built with Elicio’s AMP technology consisting of AMP-modified mutant KRAS peptide antigens and ELI-004, an AMP-modified CpG oligodeoxynucleotide adjuvant that is available as an off-the-shelf subcutaneous administration.

ELI-002 2P (2-peptide formulation) has been studied in the Phase 1 (AMPLIFY-201) trial in patients with high relapse risk mKRAS-driven solid tumors, following surgery and chemotherapy (NCT04853017). ELI-002 7P (7-peptide formulation) is currently being studied in a Phase 1/2 (AMPLIFY-7P) trial in patients with mKRAS-driven pancreatic cancer (NCT05726864). The ELI-002 7P formulation is designed to provide immune response coverage against seven of the most common KRAS mutations present in 25% of all solid tumors, thereby increasing the potential patient population for ELI-002.

About the Amphiphile Platform

Elicio’s proprietary AMP platform delivers investigational immunotherapeutics directly to the “brain center” of the immune system – the lymph nodes. Elicio believes this site-specific delivery of disease-specific antigens, adjuvants and other immunomodulators may efficiently educate, activate and amplify critical immune cells, potentially resulting in induction and persistence of potent adaptive immunity required to treat many diseases. In preclinical models, Elicio observed lymph node-specific engagement driving therapeutic immune responses of increased magnitude, function and durability. Elicio believes its AMP lymph node-targeted approach will produce superior clinical benefits compared to immunotherapies that do not engage the lymph nodes based on preclinical studies.

Elicio’s AMP platform, originally developed at the Massachusetts Institute of Technology, has broad potential in the cancer space to advance a number of development initiatives through internal activities, in-licensing arrangements or development collaborations and partnerships.

The AMP platform has been shown to deliver immunotherapeutics directly to the lymph nodes by latching on to the protein albumin, found in the local injection site, as it travels to lymphatic tissue.

Cautionary Note on Forward-Looking Statements

Certain statements contained in this communication regarding matters that are not historical facts, are forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995, known as the PSLRA. These include statements regarding Elicio’s planned clinical programs, including the timing and outcome of planned clinical trials; the timing of the expected event-driven final DFS analysis of the Phase 2 AMPLIFY-7P clinical trial; the potential of Elicio’s product candidates and platform, including the potential transformational approach Elicio’s AMP platform could represent in the treatment of mKRAS-driven tumors; the potential impact of the AMP Platform and ELI-002 in PDAC, including the potential for Elicio’s AMP platform to provide durable benefit for PDAC patients in the adjuvant setting; the potential for future expansion of ELI-002 to other indications, including mKRAS positive lung cancer and other mKRAS positive cancers; the potential benefits and effectiveness of off-the-shelf vaccine approaches; and other statements regarding management’s intentions, plans, beliefs, expectations or forecasts for the future and, therefore, you are cautioned not to place undue reliance on them. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Elicio undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise, except to the extent required by law. We use words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “future,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “continue,” “guidance,” and similar expressions to identify these forward-looking statements that are intended to be covered by the safe-harbor provisions of the PSLRA. Such forward-looking statements are based on our expectations and involve risks and uncertainties; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including, but not limited to, Elicio’s plans to develop and commercialize its product candidates, including ELI-002; the timing of initiation of Elicio’s planned clinical trials; the timing of the availability of data from Elicio’s clinical trials, including the event-driven final DFS analysis from the Phase 2 AMPLIFY-7P trial anticipated in the fourth quarter of 2025; the timing of any planned investigational new drug application or new drug application; Elicio’s plans to research, develop and commercialize its current and future product candidates; and Elicio’s estimates regarding future revenue, expenses, capital requirements and need for additional financing.

New factors emerge from time to time, and it is not possible for us to predict all such factors, nor can we assess the impact of each such factor on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. These risks are more fully discussed under the heading “Risk Factors” in Elicio’s Annual Report on Form 10-K for the year ended December 31, 2024, filed with the SEC on March 31, 2025, our Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, filed with the SEC on May 13, 2025, and our Quarterly Report on Form 10-Q for the quarter ended June 30, 2025, filed with the SEC on August 7, 2025, as updated by subsequent reports and other documents filed from time to time with the SEC. Forward-looking statements included in this release are based on information available to Elicio as of the date of this release. Elicio does not undertake any obligation to update such forward-looking statements to reflect events or circumstances after the date of this release, except to the extent required by law.

Investor Relations Contact
Brian Ritchie
LifeSci Advisors
(212) 915-2578
britchie@lifesciadvisors.com