ZyVersa Therapeutics Highlights Data Demonstrating Inflammasome Inhibition Reduces Neuroinflammation and Pathological Brain Deposition of Amyloid Beta in Alzheimer’s Disease Mouse Model
ZyVersa Therapeutics (NASDAQ: ZVSA) has highlighted new data showing how inflammasome inhibition reduces neuroinflammation and amyloid beta (Aβ) buildup in Alzheimer's disease (AD) mouse models. The research, published in Immunity journal, demonstrates that NLRP3 inhibition significantly attenuates AD pathology development.
The study reveals that initial Aβ deposition triggers NLRP3 inflammasome activation, leading to ASC specks release which enhances Aβ aggregation. This creates a cycle of inflammation and Aβ deposition in the brain. ZyVersa's Inflammasome ASC Inhibitor IC 100 shows potential as a treatment for neurodegenerative diseases by targeting ASC and inhibiting multiple inflammasome pathways.
Key findings show that NLRP3 inhibition:
- Increased degradation and elimination of Aβ in microglia through phagocytosis
- Enhanced microglial metabolic activity through increased glutamine utilization
- Improved mitochondrial function
ZyVersa Therapeutics (NASDAQ: ZVSA) ha evidenziato nuovi dati che mostrano come l'inibizione dell'inflammasoma riduca la neuroinfiammazione e l'accumulo di beta-amiloide (Aβ) nei modelli murini della malattia di Alzheimer (AD). La ricerca, pubblicata sulla rivista Immunity, dimostra che l'inibizione di NLRP3 attenua significativamente lo sviluppo della patologia AD.
Lo studio rivela che la deposizione iniziale di Aβ attiva l'inflammasoma NLRP3, portando al rilascio di ASC che aumenta l'aggregazione di Aβ. Questo crea un ciclo di infiammazione e deposizione di Aβ nel cervello. L'inibitore dell'inflammasoma ASC IC 100 di ZyVersa mostra potenziale come trattamento per le malattie neurodegenerative mirando ad ASC e inibendo più vie dell'inflammasoma.
I risultati chiave mostrano che l'inibizione di NLRP3:
- Aumenta la degradazione e l'eliminazione di Aβ nei microglia attraverso la fagocitosi
- Migliora l'attività metabolica dei microglia tramite un maggiore utilizzo di glutamina
- Migliora la funzione mitocondriale
ZyVersa Therapeutics (NASDAQ: ZVSA) ha destacado nuevos datos que muestran cómo la inhibición del inflamasoma reduce la neuroinflamación y la acumulación de beta-amiloide (Aβ) en modelos de ratón de la enfermedad de Alzheimer (AD). La investigación, publicada en la revista Immunity, demuestra que la inhibición de NLRP3 atenúa significativamente el desarrollo de la patología de AD.
El estudio revela que la deposición inicial de Aβ activa el inflamasoma NLRP3, lo que lleva a la liberación de ASC y potencia la agregación de Aβ. Esto crea un ciclo de inflamación y deposición de Aβ en el cerebro. El inhibidor de inflamasoma ASC IC 100 de ZyVersa muestra potencial como tratamiento para enfermedades neurodegenerativas al dirigirse a ASC e inhibir múltiples vías del inflamasoma.
Los hallazgos clave muestran que la inhibición de NLRP3:
- Aumenta la degradación y eliminación de Aβ en microglía a través de la fagocitosis
- Mejora la actividad metabólica de la microglía mediante un mayor uso de glutamina
- Mejora la función mitocondrial
ZYVersa Therapeutics (NASDAQ: ZVSA)는 염증소체 억제가 알츠하이머병 (AD) 쥐 모델에서 신경 염증과 아밀로이드 베타 (Aβ) 축적을 줄이는 방법을 보여주는 새로운 데이터를 강조했습니다. Immunity 저널에 발표된 연구는 NLRP3 억제가 AD 병리학 발전을 상당히 완화한다는 것을 보여줍니다.
이 연구는 초기 Aβ 침착이 NLRP3 염증소체의 활성화를 유도하여 ASC 스펙을 방출하고 Aβ 응집을 증가시킨다는 것을 밝혀냈습니다. 이는 뇌에서 염증과 Aβ 침착의 순환을 생성합니다. ZyVersa의 염증소체 ASC 억제제 IC 100은 ASC를 표적으로 하고 여러 염증소체 경로를 억제함으로써 신경퇴행성 질환 치료제로서의 잠재력을 보여줍니다.
주요 발견은 NLRP3 억제가:
- 미세아교세포에서 Aβ의 분해 및 제거를 증가시킴
- 글루타민 활용을 통해 미세아교세포의 대사 활동을 향상시킴
- 미토콘드리아 기능을 개선함
ZyVersa Therapeutics (NASDAQ: ZVSA) a mis en évidence de nouvelles données montrant comment l'inhibition de l'inflammasome réduit la neuroinflammation et l'accumulation de bêta-amyloïde (Aβ) dans des modèles murins de la maladie d'Alzheimer (AD). La recherche, publiée dans la revue Immunity, démontre que l'inhibition de NLRP3 atténue significativement le développement de la pathologie AD.
L'étude révèle que le dépôt initial d'Aβ déclenche l'activation de l'inflammasome NLRP3, conduisant à la libération de ASC qui augmente l'agrégation d'Aβ. Cela crée un cycle d'inflammation et de dépôt d'Aβ dans le cerveau. L'inhibiteur d'inflammasome ASC IC 100 de ZyVersa montre un potentiel en tant que traitement pour les maladies neurodégénératives en ciblant ASC et en inhibant plusieurs voies de l'inflammasome.
Les résultats clés montrent que l'inhibition de NLRP3:
- Augmente la dégradation et l'élimination de Aβ dans les microglies par phagocytose
- Améliore l'activité métabolique des microglies grâce à une utilisation accrue de glutamine
- Améliore la fonction mitochondriale
ZyVersa Therapeutics (NASDAQ: ZVSA) hat neue Daten hervorgehoben, die zeigen, wie die Hemmung des Inflammasoms die Neuroinflammation und den Aufbau von Beta-Amyloid (Aβ) in Mausmodellen der Alzheimer-Krankheit (AD) reduziert. Die Forschung, veröffentlicht in der Zeitschrift Immunity, zeigt, dass die Hemmung von NLRP3 die Entwicklung der AD-Pathologie erheblich abschwächt.
Die Studie zeigt, dass die anfängliche Aβ-Ablagerung die Aktivierung des NLRP3-Inflammasoms auslöst, was zur Freisetzung von ASC führt und die Aβ-Aggregation erhöht. Dies schafft einen Zyklus von Entzündung und Aβ-Ablagerung im Gehirn. Der ASC-Inhibitor IC 100 von ZyVersa zeigt Potenzial als Behandlung für neurodegenerative Erkrankungen, indem er ASC angreift und mehrere Inflammasomwege hemmt.
Wichtige Ergebnisse zeigen, dass die Hemmung von NLRP3:
- Die Abbau und Eliminierung von Aβ in Mikroglia durch Phagozytose erhöht
- Die metabolische Aktivität der Mikroglia durch erhöhten Glutaminverbrauch verbessert
- Die mitochondriale Funktion verbessert
- IC 100 demonstrated effectiveness in reducing inflammasome activation in aging mice
- Successful preclinical results showing IC 100's potential as both therapeutic and imaging biomarker
- Publication in prestigious peer-reviewed journal Immunity validates research findings
- Research still in preclinical stage, requiring further clinical trials
- Results to mouse models and laboratory cells, not yet proven in humans
Insights
ZyVersa's publication of preclinical data for its Inflammasome ASC Inhibitor IC 100 represents meaningful scientific validation for their neuroinflammation program. The research demonstrates a dual mechanism benefit: inhibiting inflammatory pathways and enhancing clearance of amyloid beta plaques, addressing two critical aspects of Alzheimer's disease pathology.
The findings published in Immunity establish a critical connection between Aβ deposition, NLRP3 inflammasome activation, and disease progression. By targeting ASC specifically, ZyVersa's approach offers a differentiated mechanism compared to other neuroinflammation candidates, potentially inhibiting multiple inflammasome pathways simultaneously.
What's particularly valuable is the corroborating evidence from human postmortem samples showing ASC expression correlation with Alzheimer's biomarkers. The potential application as both therapeutic and imaging biomarker significantly enhances IC 100's clinical utility profile.
However, investors should recognize the substantial gap between preclinical promise and clinical success, especially in neurodegenerative diseases where translation from animal models has historically proven challenging. While these results strengthen ZyVersa's scientific foundation, the company still faces the formidable task of advancing its candidate through human trials in an indication notorious for late-stage failures.
This preclinical data highlights a promising approach targeting neuroinflammatory mechanisms in Alzheimer's disease. The research confirms a critical biological feedback loop: initial Aβ deposition triggers NLRP3 activation, releasing ASC specks that enhance further Aβ aggregation, creating a self-perpetuating cycle driving disease progression.
The metabolic aspect revealed in this research is particularly noteworthy - NLRP3 inhibition not only reduced inflammation but also enhanced microglial phagocytosis through increased glutamine utilization, effectively improving the brain's natural clearance mechanisms for Aβ. This dual action represents a more comprehensive approach than strategies targeting amyloid production or clearance alone.
From a mechanistic perspective, targeting ASC has significant advantages over targeting individual inflammasome types, as it addresses multiple inflammatory pathways simultaneously. This approach could potentially overcome limitations seen with more narrowly targeted anti-inflammatory therapies in neurodegeneration.
While these findings are encouraging, it's worth noting that Alzheimer's therapeutic development is exceptionally challenging, with over 99% of candidates failing in development. The complex, multifactorial nature of AD pathology means that promising preclinical results often don't translate to human efficacy. ZyVersa will need to demonstrate that IC 100 can effectively cross the blood-brain barrier and achieve sufficient target engagement in patients to advance this promising science toward clinical utility.
- Alzheimer’s disease (AD), affecting around 6.9 million people in the US, is ranked as the seventh leading cause of death and is the most common cause of dementia among older adults.
- AD begins with buildup of amyloid beta (Aβ) plaques and neurofibrillary tangles in the brain that causes brain cells to die over time and the brain to shrink.
- The data demonstrate that initial deposition of Aβ triggers NLRP3 inflammasome activation causing release of ASC specks which rapidly enhance aggregation of Aβ. Aβ aggregates also activate NLRP3 inflammasomes thus triggering an ongoing cycle of IL-1β and ASC-mediated inflammation and Aβ deposition in the brain leading to AD progression. NLRP3 Inflammasome inhibition protected against development of AD pathology and neuroinflammation.
- These data support the potential of ZyVersa’s Inflammasome ASC Inhibitor IC 100 as an effective treatment option for patients with neurodegenerative diseases such as Alzheimer's and Parkinson’s diseases. By targeting ASC, IC 100 inhibits activation of multiple inflammasome pathways including NLRP3. Likewise, IC 100 disrupts the function of ASC specks which enhance pathological aggregation of Aβ and perpetuate the inflammatory response.
WESTON, Fla., March 12, 2025 (GLOBE NEWSWIRE) -- ZyVersa Therapeutics, Inc. (Nasdaq: ZVSA, or “ZyVersa”), a clinical stage specialty biopharmaceutical company developing first-in-class drugs for treatment of inflammatory and renal diseases, highlights newly published data demonstrating that NLRP3 Inhibition attenuates development of AD pathology (buildup of Aβ) and neuroinflammation in a mouse model of AD, thereby attenuating disease progression.
“These data strengthen support for the potential role for Inflammasome ASC Inhibitor as a treatment for Alzheimer’s and other neurological diseases, such as Parkinson’s disease,” said Stephen C. Glover, ZyVersa’s Co-founder, Chairman, CEO and President. “Data from our preclinical program demonstrate that IC 100 decreased inflammasome activation and ASC speck formation in the cortex of aging mice. A second study in postmortem brains of people with Alzheimer’s disease confirms that ASC expression correlates with Aβ and pTau in neurons. Labeled IC 100 associated with ASC in neurons in early stages of the disease thus offering potential as an imaging biomarker as well as a therapeutic option. Stay tuned for publication of data assessing the potential of IC 100 to block the damaging neuroinflammation that induces neural degeneration in Parkinson’s disease, which has been submitted to a peer reviewed journal and is currently under review.”
The new study data were published in the peer-reviewed journal, Immunity. In the publication titled, NLRP3-mediated glutaminolysis controls microglial phagocytosis to promote Alzheimer’s disease progression, the researchers report data from studies conducted in a mouse model of Alzheimer’s disease, murine microglia, and human THP-1 cells.
Key Findings
- Initial Aβ deposition directly triggers NLRP3 activation and neuroinflammation in AD mouse model, which was attenuated by NLRP3 inhibition.
- NLRP3 inhibition significantly increased degradation and elimination of Aβ in microglia via a process called phagocytosis.
- Increased microglia phagocytosis with NLRP3 inhibition was attributed to increased microglial metabolic activity: (1) NLRP3 inhibition increased glutamine utilization and α-ketoglutarate (αKG) levels; (2) αKG triggered phagocytic gene transcription, and this cellular reprogramming enhanced uptake and degradation of Aβ by microglia
- Data demonstrate an additional role for NLRP3 inhibition. In addition to attenuating damaging neuroinflammation, NLRP3 Inhibition increased mitochondrial and metabolic function, leading increased degradation and elimination of Aβ in microglia to attenuate progression of AD.
The authors concluded, “Our data strengthen NLRP3 as a master-immune regulator and an important target in the treatment of AD and dementia, both through its control on previously described inflammatory pathway and via the (metabolic) mechanism we describe here, bringing hope to the development of improved therapies for patients with this devastating condition.”
About Inflammasome ASC Inhibitor IC 100
IC 100 is a novel humanized IgG4 monoclonal antibody that inhibits the inflammasome adaptor protein ASC. IC 100 was designed to attenuate both initiation and perpetuation of the inflammatory response. It does so by binding to a specific region of the ASC component of multiple types of inflammasomes, including NLRP1, NLRP2, NLRP3, NLRC4, AIM2, and Pyrin. Intracellularly, IC 100 binds to ASC monomers, inhibiting inflammasome formation, thereby blocking activation of IL-1β early in the inflammatory cascade. IC 100 also binds to ASC in ASC Specks, both intracellularly and extracellularly, further blocking activation of IL-1β and the perpetuation of the inflammatory response that is pathogenic in inflammatory diseases. Because active cytokines amplify adaptive immunity through various mechanisms, IC 100, by attenuating cytokine activation, also attenuates the adaptive immune response. The lead indication for IC 100 is obesity with certain metabolic complications. To review a white paper summarizing the mechanism of action and preclinical data for IC 100, Click Here.
About ZyVersa Therapeutics, Inc.
ZyVersa (Nasdaq: ZVSA) is a clinical stage specialty biopharmaceutical company leveraging advanced proprietary technologies to develop first-in-class drugs for patients with inflammatory or kidney diseases with high unmet medical needs. We are well positioned in the rapidly emerging inflammasome space with a highly differentiated monoclonal antibody, Inflammasome ASC Inhibitor IC 100, and in kidney disease with phase 2 Cholesterol Efflux Mediator™ VAR 200. The lead indication for IC 100 is obesity and its associated metabolic complications, and for VAR 200, focal segmental glomerulosclerosis (FSGS). Each therapeutic area offers a “pipeline within a product,” with potential for numerous indications. The total accessible market is over
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New factors emerge from time-to-time, and it is not possible for ZyVersa to predict all such factors, nor can ZyVersa 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. Forward-looking statements included in this press release are based on information available to ZyVersa as of the date of this press release. ZyVersa disclaims any obligation to update such forward-looking statements to reflect events or circumstances after the date of this press release, except as required by applicable law.
This press release does not constitute an offer to sell, or the solicitation of an offer to buy, any securities.
Corporate, Media, and IR Contact:
Karen Cashmere
Chief Commercial Officer
kcashmere@zyversa.com
786-251-9641
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