S1P/S1PR News - LARVOL Sigma

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||||||||||  fingolimod / Generic mfg.
Trial completion:  Study of Efficacy and Safety of Fingolimod (Gilenya) 0.5 mg in Chinese Patients With Relapsing Multiple Sclerosis (RMS) Patients (clinicaltrials.gov) -  Apr 2, 2025
P4, N=98, Completed,  Sponsor: Novartis Pharmaceuticals
Active, not recruiting --> Completed

|||||||||| fingolimod / Generic mfg.
Journal: Early and active treatment with fingolimod (Pubmed Central) - Apr 2, 2025
Fingolimod offers better compliance and significantly improves patients' quality of life compared to injection therapies especially in pediatric population, reducing injection associated anxiety and risk of discontinuation. It appears to be safe and well tolerated and may be used as first line treatment in the highly active and aggressive disease course of pediatric onset multiple sclerosis.

|||||||||| Journal: Recommendations for essential medicines for multiple sclerosis in low-resource settings. (Pubmed Central) - Apr 1, 2025
It appears to be safe and well tolerated and may be used as first line treatment in the highly active and aggressive disease course of pediatric onset multiple sclerosis. Recommendations for the minimum essential DMTs for MS in low-resource settings were developed based on robust consideration of evidence and relevant context.

|||||||||| Tysabri (natalizumab) / Biogen, Royalty, Ocrevus (ocrelizumab) / Roche, Rituxan (rituximab) / Roche
Journal: Reevaluation of the gastrointestinal methanogenic archaeome in multiple sclerosis and its association with treatment. (Pubmed Central) - Apr 1, 2025
Most MS patients were female (80/115), aged 25-72 years (median: 44.5), and 70% were undergoing treatment, including dimethyl fumarate (n = 21), fingolimod (n = 20), glatiramer acetate (n = 14), interferon (n = 18), natalizumab (n = 6), or ocrelizumab/rituximab (n = 1)...By focusing on methanogens, we aim to uncover novel insights into their role in MS, potentially revealing new biomarkers or therapeutic targets. This research is crucial for enhancing our understanding of the gut microbiome's impact on MS and improving patient management.

|||||||||| fingolimod / Generic mfg.
Preclinical, Journal: Fingolimod ameliorates amyloid deposition and neurodegeneration in APP/PS1 mouse model of Alzheimer's disease. (Pubmed Central) - Mar 31, 2025
This research is crucial for enhancing our understanding of the gut microbiome's impact on MS and improving patient management. This study illustrates that fingolimod effectively ameliorates multiple pathological features of AD, highlighting its potential as a promising therapeutic candidate for the disease.

|||||||||| Mayzent (siponimod) / Novartis, fingolimod / Generic mfg.
Journal, Adverse events: Identifying cardiovascular toxicity associated with sphingosine 1-phosphate receptor modulators: A case-control study based on the FDA adverse event reporting system. (Pubmed Central) - Mar 29, 2025
This study illustrates that fingolimod effectively ameliorates multiple pathological features of AD, highlighting its potential as a promising therapeutic candidate for the disease. In this study, signals of bradyarrhythmias, hypertension, QT interval prolongation, central nervous system ischemia, tachyarrhythmias, and ischaemic heart disease were significant with one or more S1PR modulators, which warrant clinical attention and ongoing monitoring.

|||||||||| Mayzent (siponimod) / Novartis
Journal: Siponimod inhibits microglial inflammasome activation. (Pubmed Central) - Mar 28, 2025
Our data indicate that siponimod achieves its anti-inflammatory effects by inhibiting inflammasome activation in microglia via S1P1 antagonism. This process is inferred to play a crucial role in mitigating the secondary progression of multiple sclerosis, where microglial activation in the gray matter is considered a key pathological factor.

|||||||||| Review, Journal: Therapeutic Advances in Pediatric Multiple Sclerosis. (Pubmed Central) - Mar 28, 2025
We will also review the safety and efficacy of different monoclonal antibodies that are commonly prescribed for multiple sclerosis. We will then examine induction versus escalation treatment strategies and conclude with discussions on treatment considerations in POMS patients.

|||||||||| Velsipity (etrasimod) / Pfizer
Clinical, P2 data, Journal: Efficacy and safety of etrasimod in alopecia areata: A multicentre, randomized, double-blind, placebo-controlled, Phase 2 study. (Pubmed Central) - Mar 27, 2025
P2
The etrasimod clinical programme for AA has been discontinued. Etrasimod was well tolerated, and its safety profile was consistent with other etrasimod studies to date.

|||||||||| fingolimod / Generic mfg.
Preclinical, Journal: Lipidated IL-22 Alone or Combined with Immunomodulatory Agents Improves Disease Endpoints and Promotes Mucosal Healing in a Mouse Model of Chronic Dextran Sodium Sulfate-Induced Colitis. (Pubmed Central) - Mar 27, 2025
Etrasimod was well tolerated, and its safety profile was consistent with other etrasimod studies to date. Given the challenges in achieving long-term remission in IBD due to inflammation and mucosal damage, lipidated IL-22 presents a promising treatment option that directly promotes mucosal healing, unlike traditional immunomodulatory therapies.

|||||||||| Ocrevus (ocrelizumab) / Roche
Journal: Extensive T-Cell Profiling Following SARS-CoV-2 mRNA Vaccination in Multiple Sclerosis Patients Treated with DMTs. (Pubmed Central) - Mar 27, 2025
While humoral immune response was impaired in pwMS during ocrelizumab and fingolimod treatment, there was evidence of a compensatory upregulation of subpopulations of SARS-CoV-2-specific CD4+ T cells at low levels of seroconversion in pwMS. In conclusion, our results provide important insights into the mechanisms of the adaptive immune response in pwMS following SARS-CoV-2 mRNA vaccination.

|||||||||| fingolimod / Generic mfg.
Journal: Effects of systemic fingolimod treatment on anterior segment parameters and tear film functions. (Pubmed Central) - Mar 27, 2025
The mean TBUT was significantly higher at the six-month visit compared to baseline and the one-month visit (p0-6 < 0.001, p1-6 < 0.001), but there was no statistically significant difference between baseline and month 1 (p0-1 = 0.419). Systemic use of fingolimod may increase Schirmer I test and TBUT values in MS patients without altering other anterior segment parameters within 6?months.

|||||||||| Velsipity (etrasimod) / Pfizer
Journal: Etrasimod Corticosteroid-Free Efficacy, Impact of Concomitant Corticosteroids on Efficacy and Safety, and Corticosteroid-Sparing Effect in UC: Analyses of the ELEVATE UC Clinical Programme. (Pubmed Central) - Mar 27, 2025
P3
CS-free remission was achieved in the CS subgroup. Safety was consistent, with no increase in infections.

|||||||||| Review, Journal: Small Molecules in the Treatment of Acute Severe Ulcerative Colitis: A Review of Current Evidence. (Pubmed Central) - Mar 27, 2025
Conversely, it is necessary to investigate whether infliximab can be effectively replaced or surpassed by other approved biological agents and small molecules as first-line therapy after steroid resistance. This review aims to summarise the available evidence on small molecules, specifically Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators.

|||||||||| fingolimod / Generic mfg.
Journal: Pre-existing parasympathetic dominance seems to cause persistent heart rate slowing after 6 (Pubmed Central) - Mar 26, 2025
This review aims to summarise the available evidence on small molecules, specifically Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators. Our patients with prolonged HR slowing upon fingolimod initiation could not downregulate cardiovagal modulation upon standing up even before fingolimod initiation, and 6

|||||||||| Zeposia (ozanimod) / BMS
Journal: Ozanimod-associated macular edema. (Pubmed Central) - Mar 26, 2025
Our patients with prolonged HR slowing upon fingolimod initiation could not downregulate cardiovagal modulation upon standing up even before fingolimod initiation, and 6 No abstract available

|||||||||| fingolimod / Generic mfg.
Preclinical, Retrospective data, Journal, Checkpoint inhibition: Microwave ablation combined with immune checkpoint inhibitor enhanced the antitumor immune activation and memory in rechallenged tumor mouse model. (Pubmed Central) - Mar 25, 2025
Moreover, the efficacy of the combinational therapy depended on the migration of T cells from TdLNs to tumor site. In summary, we proposed a potentially effective combined treatment regimen and have elucidated the underlying cellular mechanisms that underpin its efficacy.

|||||||||| fingolimod / Generic mfg.
Review, Journal: The potential capacities of FTY720: Novel therapeutic functions, targets, and mechanisms against diseases. (Pubmed Central) - Mar 23, 2025
Additionally, it summarizes FTY720's derivation and development process, the characterization and mechanism of the structure of FTY720-P bound to S1PRs, the clinical safety profile, future challenges, and potential strategies to address them. These insights aim to guide future research and applications of FTY720, maximizing its therapeutic potential.

|||||||||| Mayzent (siponimod) / Novartis
Fatigue, depression, and QOL changes due to continuous administration of Siponimod (Poster Venue; Osaka International Convention Center 3F Event Hall) - Mar 23, 2025 - Abstract #JSNE2025JSNE_1256;

|||||||||| Zeposia (ozanimod) / BMS, Velsipity (etrasimod) / Pfizer
Journal: Matching-adjusted indirect comparisons of efficacy outcomes between etrasimod and ozanimod for moderately to severely active ulcerative colitis. (Pubmed Central) - Mar 21, 2025
MAIC results suggest that patients receiving etrasimod have similar induction results but are more likely to have clinical response and clinical remission at the end of the maintenance phase compared with patients receiving ozanimod. Despite the approach to ensure similarity between the trials by weighting, residual imbalance is possible, and results should be interpreted in the context of the assumptions.

||||||||||  Zeposia (ozanimod) / BMS
Enrollment open:  Study to Evaluate the Effectiveness and Safety of Ozanimod Compared to Fingolimod in Children and Adolescents With Relapsing Remitting Multiple Sclerosis (clinicaltrials.gov) -  Mar 21, 2025
P3, N=194, Recruiting,  Sponsor: Celgene
Despite the approach to ensure similarity between the trials by weighting, residual imbalance is possible, and results should be interpreted in the context of the assumptions. Not yet recruiting --> Recruiting

|||||||||| fingolimod / Generic mfg.
Journal: Positive allosteric modulation of AMPA receptors via PF4778574 leads to reduced demyelination and clinical disability in experimental models of multiple sclerosis. (Pubmed Central) - Mar 20, 2025
Additionally, we explored the effects of PF4778574 in comparison and in combination with the immunomodulatory agent fingolimod, and investigated the impact on Cuprizone induced toxic demyelination...PF4778574 demonstrates promise in mitigating EAE effects, especially in terms of clinical disability and demyelination. These results suggest AMPA-PAMs as potential targets of interest for MS treatment beyond immunomodulatory approaches.

|||||||||| Mavenclad (cladribine) / EMD Serono, fingolimod / Generic mfg.
Journal: European experience of cladribine tablets in elderly patients with multiple sclerosis: Could it be the last treatment? (Pubmed Central) - Mar 19, 2025
The first one had 2 relapses after switching from fingolimod with a 2-month interval between treatments. The 2 remaining were na

||||||||||  fingolimod / Generic mfg.
Trial completion date:  Fingolimod for the Abrogation of Interstitial Fibrosis and Tubular Atrophy Following Kidney Transplantation (clinicaltrials.gov) -  Mar 17, 2025
P2, N=20, Enrolling by invitation,  Sponsor: The Methodist Hospital Research Institute
The 2 remaining were na Trial completion date: Sep 2025 --> Dec 2027

|||||||||| Review, Journal: Paradigm Shift in Inflammatory Bowel Disease Management: Precision Medicine, Artificial Intelligence, and Emerging Therapies. (Pubmed Central) - Mar 17, 2025
Emerging therapies, precision medicine, and ongoing research into novel targets promise to reshape the IBD treatment landscape. As these advances continue to unfold, IBD patients can anticipate a brighter future, one marked by more effective, personalized, and accessible treatments.

|||||||||| fingolimod / Generic mfg.
Journal: PLZF-expressing CD4+ T cells promote tissue-resident memory T cells in breaking immune tolerance in allergic asthma via IL-15/IL-15R? signaling. (Pubmed Central) - Mar 16, 2025
Thus, targeting PLZF or the IL-15/IL-15R? pathway may represent a promising therapeutic strategy for treating asthma.

|||||||||| Rinvoq (upadacitinib) / AbbVie
Journal, HEOR, Cost-effectiveness: Cost-Effectiveness Analysis of Upadacitinib in Patients With Moderately to Severely Active Ulcerative Colitis in Greece. (Pubmed Central) - Mar 14, 2025
pathway may represent a promising therapeutic strategy for treating asthma. Upadacitinib was estimated to be the most effective and cost-effective treatment among all advanced treatments for moderately to severely active UC in Greece.

|||||||||| Remicade (infliximab) / J&J, Zeposia (ozanimod) / BMS, Rinvoq (upadacitinib) / AbbVie
Journal, Real-world evidence: Real-world prevalence of potential drug-drug interactions associated with oral advanced therapies indicated for ulcerative colitis. (Pubmed Central) - Mar 14, 2025
For JAK inhibitors, these were COVID-19 vaccines (30.7% and 31.4%), infliximab (8.5% and 20.2%), fluconazole (6.1% and 6.8%), and azathioprine (5.5% and 13.0%)...Comorbidities and polypharmacy among patients with UC pose a high risk of DDIs for oral advanced therapies, and required pre-treatment clinical assessments can be complicated. This justifies a thorough review of patient profiles for prescribers considering novel treatment options.

|||||||||| Journal, Adverse events, Real-world evidence: Herpes Zoster Infections With Multiple Sclerosis Disease-Modifying Therapies: A Real-World Pharmacovigilance Study. (Pubmed Central) - Mar 14, 2025
We queried the Food and Drug Administration Adverse Event Reporting System (FAERS) and OpenVigil 2.1 for reports of HZ involving immunosuppressive MS DMTs (ocrelizumab [OCR], ofatumumab [OFT], rituximab [RTX], natalizumab [NTZ], alemtuzumab, dimethyl fumarate and diroximel fumarate [DRF], fingolimod [FING], siponimod [SIP], ozanimod [OZ], mitoxantrone [MITO], cladribine [CLAD], and teriflunomide [TERF]) and calculated reporting odds ratios and their 95% CIs...Immunosuppressive MS DMTs are associated with greater HZ reporting in the FAERS. These findings emphasize the importance of pre-DMT HZ vaccination because of avoidable HZ infections.

|||||||||| fingolimod / Generic mfg.
Journal: Protection conferred by mucosal novel bivalent Klebsiella pneumoniae vaccine immunization associates with presence of lung CD4+ TRM. (Pubmed Central) - Mar 14, 2025
Transcriptomic analysis of total lung tissues from mice treated by FTY720 (S1PR1 inhibitor that blocks lymphocyte egress from secondary lymphoid structures) showed that cell activation, cytokine secretion and enhancement of the killing ability of neutrophils were related to the mechanism of protection against K. pneumoniae infection. These findings indicate that GlnH and FimA are effective candidate bivalent vaccine to fight K. pneumoniae infection.

|||||||||| fingolimod / Generic mfg.
Preclinical, Journal: Therapeutic potential of Pranlukast against cuprizone-induced inflammatory demyelination and sensory impairment in mice: comparison with Fingolimod. (Pubmed Central) - Mar 14, 2025
Cuprizone and Pranlukast groups presented more microglia/macrophages in the CC, but fewer presenting reactive microglia/macrophages and less NOS2 staining in pranlukast-treated when compared to the cuprizone group, while fingolimod treatment prevented the increase in Iba1 in the CC. In summary, this study demonstrated that pranlukast is a good candidate as a novel drug for use in conditions of inflammatory demyelination, such as MS, by restoring function through modulation of the inflammatory environment.

|||||||||| fingolimod / Generic mfg.
Journal: RBM10 deficiency promotes brain metastasis by modulating sphingolipid metabolism in a BBB model of EGFR mutant lung adenocarcinoma. (Pubmed Central) - Mar 12, 2025
In summary, this study demonstrated that pranlukast is a good candidate as a novel drug for use in conditions of inflammatory demyelination, such as MS, by restoring function through modulation of the inflammatory environment. This study offers insights into the potential mechanisms of brain metastasis in LUAD and suggests a possible therapeutic target for further investigation.

|||||||||| LX 2931 / Lexicon Pharma
Preclinical, Journal: Dual action of sphingosine 1-phosphate pathway in in vitro models of global cerebral ischemia. (Pubmed Central) - Mar 12, 2025
In the same model we investigated the effect of the inhibitor of S1P lyase (SPL), LX2931, the selective antagonists of S1P2, JTE-013, and S1P3, CAY10444, quantifying the cell death in the CA1 region by propidium iodide fluorescence, and morphological and tissue organization alterations by immunohistochemistry and confocal microscopy...Our results reveal a dual role of S1P pathway in brain ischemia: intracellular S1P, degraded via SPL, appears to be beneficial whereas signaling via S1P2 and S1P3 is detrimental to the disease. These findings support the notion that SPL, S1P2 and S1P3 are promising therapeutic targets in brain ischemia.

|||||||||| Clinical, Review, Journal: Rituximab for people with multiple sclerosis. (Pubmed Central) - Mar 12, 2025
There is an increased risk of serious (hospital-treated) infections with rituximab compared with other DMTs, although the absolute risk is low. High-quality (prospectively registered) NRSIs should be conducted to draw more reliable conclusions about the potential benefits and harms of rituximab in people with MS.

|||||||||| fingolimod / Generic mfg.
Journal: Enhancing therapeutic efficacy of Fingolimod via Intranasal Delivery in an Ethidium Bromide-induced Model of Multiple Sclerosis. (Pubmed Central) - Mar 10, 2025
High-quality (prospectively registered) NRSIs should be conducted to draw more reliable conclusions about the potential benefits and harms of rituximab in people with MS. This study demonstrates the successful development of FNG-SLNs to enhance the therapeutic efficacy of FNG for the treatment of multiple sclerosis.

||||||||||  Zeposia (ozanimod) / BMS
Trial completion date, Trial primary completion date:  A Study of Ozanimod in Pregnant Women With Ulcerative Colitis and Their Offspring (clinicaltrials.gov) -  Mar 10, 2025
P=N/A, N=1182, Not yet recruiting,  Sponsor: Bristol-Myers Squibb
This study demonstrates the successful development of FNG-SLNs to enhance the therapeutic efficacy of FNG for the treatment of multiple sclerosis. Trial completion date: Jun 2032 --> Jun 2033 | Trial primary completion date: Jun 2032 --> Jun 2033

|||||||||| fingolimod / Generic mfg.
Review, Journal: Severe disease activation after fingolimod discontinuation in a pediatric multiple sclerosis patient: A case report and literature review. (Pubmed Central) - Mar 9, 2025
Despite prompt high-dose corticosteroids, plasma exchange and prolonged rehabilitation therapy, significant residual deficits involving cognition, balance and vision remain from the attack. This case underscores that pediatric patients are also at risk of severe disease deterioration after fingolimod withdrawal and require close monitoring when switching therapies.

|||||||||| Velsipity (etrasimod) / Pfizer, obefazimod (ABX464) / Abivax
SYNERGISTIC REDUCTION OF INFLAMMATORY CYTOKINES WITH OBEFAZIMOD AND ETRASIMOD IN COMBINATION TREATMENT VS. EITHER MONOTHERAPY IN A MOUSE MODEL OF INFLAMMATORY BOWEL DISEASE () - Mar 8, 2025 - Abstract #DDW2025DDW_6172;

|||||||||| Velsipity (etrasimod) / Pfizer
THE EFFICACY AND SAFETY OF ETRASIMOD IN MILDLY TO MODERATELY ACTIVE ULCERATIVE COLITIS: RESULTS FROM THE GLADIATOR TRIAL () - Mar 8, 2025 - Abstract #DDW2025DDW_5701;

|||||||||| Velsipity (etrasimod) / Pfizer
4435: IMIBD_DAP: Immunology, Microbiology & Inflammatory Bowel Diseases (IMIBD) Section Distinguished Abstract Plenary () - Mar 8, 2025 - Abstract #DDW2025DDW_5695;
This case underscores that pediatric patients are also at risk of severe disease deterioration after fingolimod withdrawal and require close monitoring when switching therapies. Description: This session highlights the best of the best in basic and clinical science inflammatory bowel diseases research submitted to DDW 2025 and will cover novel genetic variants and gene expression patterns linked with disease, recent findings on the role of the gut microbiota on disease pathogenesis and the latest clinical trials controlled clinical trials in the field.Learning Objectives:

|||||||||| Velsipity (etrasimod) / Pfizer
THE IMPACT OF ETRASIMOD ON NEUTROPHILS IN THE ELEVATE UC CLINICAL PROGRAM () - Mar 8, 2025 - Abstract #DDW2025DDW_3809;

|||||||||| Zeposia (ozanimod) / BMS
IMPACT OF OZANIMOD (OZA) ON CIRCULATING NEUTROPHILS: RESULTS FROM THE PHASE 3 JAPANESE TRUE NORTH (J-TN) STUDY OF PATIENTS (PTS) WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS (UC) () - Mar 8, 2025 - Abstract #DDW2025DDW_3797;

|||||||||| Velsipity (etrasimod) / Pfizer
ETRASIMOD FOR THE TREATMENT OF ULCERATIVE COLITIS: UP TO 4 YEARS OF SAFETY DATA FROM THE GLOBAL CLINICAL PROGRAM () - Mar 8, 2025 - Abstract #DDW2025DDW_3794;

|||||||||| Velsipity (etrasimod) / Pfizer
ETRASIMOD EFFICACY IN PATIENTS WITH MILDLY TO MODERATELY ACTIVE ULCERATIVE COLITIS (MODIFIED MAYO SCORE 4 () - Mar 8, 2025 - Abstract #DDW2025DDW_3778;

|||||||||| Velsipity (etrasimod) / Pfizer
EFFICACY OF ETRASIMOD AT WEEK 52 AMONG BIOLOGIC/JANUS KINASE INHIBITOR-NA () - Mar 8, 2025 - Abstract #DDW2025DDW_3776;

|||||||||| Journal: Guselkumab (Tremfya) for ulcerative colitis. (Pubmed Central) - Mar 7, 2025
Description: This session highlights the best of the best in basic and clinical science inflammatory bowel diseases research submitted to DDW 2025 and will cover novel genetic variants and gene expression patterns linked with disease, recent findings on the role of the gut microbiota on disease pathogenesis and the latest clinical trials controlled clinical trials in the field.Learning Objectives: No abstract available

|||||||||| fingolimod / Generic mfg.
Journal: Investigating treatment alternatives for fingolimod in patients with multiple sclerosis developed refractory fingolimod-related genital Human Papilloma Virus (HPV) infection. (Pubmed Central) - Mar 6, 2025
Our preliminary results revealed that anti-CD20s agents could be considered safe in patients treated with fingolimod who had to discontinue treatment due to persistent HPV infection. Larger studies are needed to warrant our data.

|||||||||| Clinical, Retrospective data, Review, Journal: Comparing the efficacy of divozilimab and second-line treatments for relapsing-remitting multiple sclerosis in the Russian Federation: a systematic review and network meta-analysis (Pubmed Central) - Mar 6, 2025
Larger studies are needed to warrant our data. Systematic literature review and network meta-analysis revealed statistically significant superiority of divozilimab over cladribine and fingolimod and absence of statistically significant differences with alemtuzumab, ocrelizumab, ofatumumab and natalizumab in the annual relapse rate during 2 years of treatment.

|||||||||| fingolimod / Generic mfg.
Preclinical, Journal: Targeted immunotherapy with sphingosine-1-phosphate improves myocardial contractility and mitochondrial function in a novel murine ex vivo perfusion and transplantation model. (Pubmed Central) - Mar 6, 2025
Systematic literature review and network meta-analysis revealed statistically significant superiority of divozilimab over cladribine and fingolimod and absence of statistically significant differences with alemtuzumab, ocrelizumab, ofatumumab and natalizumab in the annual relapse rate during 2 years of treatment. Donor hearts perfused with hypothermic, acellular perfusate and S1P demonstrated improved post-transplantation heart function, decreased histologic injury, and increased mitochondrial performance compared to cold-static CSP, representing a potential strategy to mitigate IRI within heart transplantation.

|||||||||| acetylcysteine solution / Generic mfg., fingolimod / Generic mfg.
Journal: A nasally administrated reactive oxygen species-responsive carrier-free gene delivery nanosystem for Alzheimer's disease combination therapy. (Pubmed Central) - Mar 6, 2025
Upon reaching the brain, FTBR responded to the elevated ROS at the pathological site, releasing siBACE1 and fingolimod. Administration of FTBR-NAC improved cognitive function in AD mice, demonstrating the high therapeutic efficacy of this relatively simple nanosystem.



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