Not provided
Not provided
Not provided
Not provided
Not provided
Sponsor resource allocation
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The goal of this Phase 2 Open Label study is to evaluate long-term safety, tolerability, and efficacy of XPro1595 on measures of cognition, function and brain quality in individuals with Alzheimer's Disease.
This study is designed as a Phase 2, open label study investigating the safety, tolerability, and efficacy of XPro1595 in patients with Alzheimer's Disease (AD). The planned dose is 1.0 mg/kg of XPro1595 for all subjects that completed a previous Phase 1 or Phase 2 study with XPro1595.
Each enrolled patient will be treated with 1.0 mg/kg of XPro1595 as a subcutaneous injection once a week for 55 or 74 weeks, for a total exposure to XPro1595 of up to 78 weeks (18 months), depending on their previous study. Blood sampling for clinical lab analyses, physical exam findings, ECG and C-SSRS will be collected throughout the study to assess the safety and tolerability of XPro1595. Imaging endpoints (MRI), blood sampling for neuroinflammatory and neurodegenerative biomarkers, clinical ratings (CDR-SB, ADCS-MCI ADL, NPI-12) and cognitive performance assessed via the EMACC will be collected at screening and at Weeks 12, 24, 36, and 48. Depending on the parent study, some or all of these assessments may also be made at Weeks 55, 60 or 74.
All patients that completed 4 weeks of dosing and the week 5 PK draw in the Phase 1 PK Lead-In or completed the treatment period and End of Study (EOS) assessments in a Phase 2 study are eligible to enroll into the OLE study. All patients enrolled, including those treated with placebo in the parent study, will receive 1.0 mg/kg XPro1595. Randomized treatment will remain blinded until the parent study database is locked, the study is unblinded and results for their prior study are released.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental: 1.0 mg/kg XPro1595 | Experimental | Patients will receive XPro1595. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| XPro1595 | Drug | Each enrolled patient will be treated with 1.0 mg/kg of XPro1595 as a subcutaneous injection once a week for 55, or 74 weeks, for a total exposure to XPro1595 of up to 78 weeks (18 months), depending on their previous study. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants who experience adverse events and serious adverse events | Change from Baseline to Weeks 55, or 74 in the OLE Study Clinically significant abnormalities of laboratory values, physical findings, electrocardiogram (ECG) findings and other safety assessments will be recorded as adverse events if the findings meet the defined criteria for adverse events. | Weeks 55, or 74 in the OLE Study |
| Measure | Description | Time Frame |
|---|---|---|
| To evaluate the change in cognitive performance following administration of open-label XPro1595 | Change from Baseline on the Early and Mild Alzheimer's Cognitive Composite (EMACC) (Jaeger 2017) made up of the following tests:
|
Not provided
Inclusion Criteria:
Patients are eligible to be included in the study only if all the following criteria apply:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Tara Lehner | INmune Bio | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| KaRa MINDS | Macquarie Park | New South Wales | 2113 | Australia | ||
| Neuro Trials Victoria Pty Ltd T/A NeuroCentrix |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16705109 | Background | Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006 May 17;295(19):2275-85. doi: 10.1001/jama.295.19.2275. | |
| 21239393 |
| Label | URL |
|---|---|
| Alzheimer's Association annual report releasing statistics regarding Alzheimer's disease | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
An Open-Label Extension of XPro1595 in Patients with Alzheimer's Disease (AD) That Have Completed a Phase 2 Study with XPro1595
Not provided
Not provided
Not provided
Not provided
|
| Week 55 in the OLE Study |
| To evaluate the change in cognition and global function following administration of open-label XPro1595 | Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Week 55 in the OLE study for the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) | Week 55 in the OLE Study |
| To evaluate the change in non-cognitive behavioral symptoms following open-label administration of XPro1595 | Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Week 55 in the OLE study on the Neuropsychiatric Inventory (NPI-12) study partner items. The NPI-12 total score is calculated by adding the scores of the domains (each domain score ranges from 0 to 12). The NPI-12 total score is based upon the first 10 items and ranges from (0 to 10) with higher scores indicating greater behavioral impairment. | Week 55 in the OLE Study |
| To evaluate the change Change from Baseline on the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS- MCI- ADL) | Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Week 55 in the OLE study on the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS- MCI- ADL) The 23-item Alzheimer's Disease Cooperative Study - Mild Cognitive Impairment Activities of Daily Living (ADCS-MCI-ADL) Scale has good test-retest reliability, will be utilized to assess performance functioning in MCI patients (Galasko et al., 1997; Douglas Galasko et al., 2006; Pedrosa et al., 2010). | Week 55 in the OLE Study |
| To evaluate the change on blood inflammatory and neurodegeneration biomarkers following open-label administration of XPro1595 (on blood inflammatory and neurodegeneration biomarker amyloid) | Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study or for those in the PK Lead-In Study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Weeks 55, or 74 in the OLE study on blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker amyloid). | Weeks 55, or 74 in the OLE Study |
| To evaluate the change on blood inflammatory and neurodegeneration biomarkers following open-label administration of XPro1595 (on blood inflammatory and neurodegeneration biomarker pTau) | Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study or for those in the PK Lead-In Study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Weeks 55, or 74 in the OLE study on blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker pTau). | Weeks 55, or 74 in the OLE Study |
| To evaluate the change on imaging neuroinflammation following open-label administration of XPro1595 | Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study or for those in the PK Lead-In Study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Weeks 55, or 74 in the OLE study in Magnetic Resonance Imaging (MRI) neuroinflammation (White matter Free Water). | Weeks 55, or 74 in the OLE Study |
| To evaluate the change on axonal integrity following open-label administration of XPro1595 | Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study or for those in the PK Lead-In Study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Weeks 55, or 74 or in the OLE study in MRI Apparent Fiber Density (AFD). | Weeks 55, or 74 in the OLE Study |
| To evaluate the change in Everyday Cognition (ECog) following open-label administration of XPro1595 | Change from Baseline in the double-blind study (for those on XPro1595 during the double-blind study) or Change from Baseline in the OLE Study (for those on placebo during the double-blind study) to Week 55 in the OLE study on Everyday Cognition (ECog). | Week 55 in the OLE Study |
| Carlton |
| Victoria |
| 3053 |
| Australia |
| Austin Health | Ivanhoe | Victoria | 3079 | Australia |
| Australian Alzheimer's Research Foundation | Perth | Western Australia | 6009 | Australia |
| Chance SA, Clover L, Cousijn H, Currah L, Pettingill R, Esiri MM. Microanatomical correlates of cognitive ability and decline: normal ageing, MCI, and Alzheimer's disease. Cereb Cortex. 2011 Aug;21(8):1870-8. doi: 10.1093/cercor/bhq264. Epub 2011 Jan 14. |
| 27470609 | Background | Chou RC, Kane M, Ghimire S, Gautam S, Gui J. Treatment for Rheumatoid Arthritis and Risk of Alzheimer's Disease: A Nested Case-Control Analysis. CNS Drugs. 2016 Nov;30(11):1111-1120. doi: 10.1007/s40263-016-0374-z. |
| 22966039 | Background | Clark I, Atwood C, Bowen R, Paz-Filho G, Vissel B. Tumor necrosis factor-induced cerebral insulin resistance in Alzheimer's disease links numerous treatment rationales. Pharmacol Rev. 2012 Oct;64(4):1004-26. doi: 10.1124/pr.112.005850. Epub 2012 Sep 10. |
| 16569464 | Background | Alvarez A, Cacabelos R, Sanpedro C, Garcia-Fantini M, Aleixandre M. Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in Alzheimer disease. Neurobiol Aging. 2007 Apr;28(4):533-6. doi: 10.1016/j.neurobiolaging.2006.02.012. Epub 2006 Mar 29. |
| 19070941 | Background | Buchhave P, Zetterberg H, Blennow K, Minthon L, Janciauskiene S, Hansson O. Soluble TNF receptors are associated with Abeta metabolism and conversion to dementia in subjects with mild cognitive impairment. Neurobiol Aging. 2010 Nov;31(11):1877-84. doi: 10.1016/j.neurobiolaging.2008.10.012. Epub 2008 Dec 13. |
| Background | Branders S, Bernard G and Pereira A. Leveraging historical data for high-dimensional regression adjustment, a machine learning approach. PSI annual conference, Amsterdam, 3 to 6 June 2018. |
| Background | Arnason et al., Neurology. 53, 457-465 (1999) |
| 26894207 | Background | Bradshaw MJ, Mobley BC, Zwerner JP, Sriram S. Autopsy-proven demyelination associated with infliximab treatment. Neurol Neuroimmunol Neuroinflamm. 2016 Jan 27;3(2):e205. doi: 10.1212/NXI.0000000000000205. eCollection 2016 Apr. No abstract available. |
| 9100663 | Background | Dickson DW. The pathogenesis of senile plaques. J Neuropathol Exp Neurol. 1997 Apr;56(4):321-39. doi: 10.1097/00005072-199704000-00001. |
| Background | Draft FDA Guidance for Industry: Adjusting for covariates in randomized clinical trials for drugs and biologics. Revision 1 May 2021 Biostatistics (https://www.fda.gov/media/148910/download). |
| 32808747 | Background | Finsterwalder S, Vlegels N, Gesierich B, Araque Caballero MA, Weaver NA, Franzmeier N, Georgakis MK, Konieczny MJ, Koek HL; Dominantly Inherited Alzheimer Network (DIAN); Karch CM, Graff-Radford NR, Salloway S, Oh H, Allegri RF, Chhatwal JP; DELCODE study group; Jessen F, Duzel E, Dobisch L, Metzger C, Peters O, Incesoy EI, Priller J, Spruth EJ, Schneider A, Fliessbach K, Buerger K, Janowitz D, Teipel SJ, Kilimann I, Laske C, Buchmann M, Heneka MT, Brosseron F, Spottke A, Roy N, Ertl-Wagner B, Scheffler K; Alzheimer's Disease Neuroimaging Initiative (ADNI); Utrecht VCI study group; Seo SW, Kim Y, Na DL, Kim HJ, Jang H, Ewers M, Levin J, Schmidt R, Pasternak O, Dichgans M, Biessels GJ, Duering M. Small vessel disease more than Alzheimer's disease determines diffusion MRI alterations in memory clinic patients. Alzheimers Dement. 2020 Nov;16(11):1504-1514. doi: 10.1002/alz.12150. Epub 2020 Aug 18. |
| 1745413 | Background | Fillit H, Ding WH, Buee L, Kalman J, Altstiel L, Lawlor B, Wolf-Klein G. Elevated circulating tumor necrosis factor levels in Alzheimer's disease. Neurosci Lett. 1991 Aug 19;129(2):318-20. doi: 10.1016/0304-3940(91)90490-k. |
| 29653606 | Background | Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E, Molinuevo JL, Montine T, Phelps C, Rankin KP, Rowe CC, Scheltens P, Siemers E, Snyder HM, Sperling R; Contributors. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018 Apr;14(4):535-562. doi: 10.1016/j.jalz.2018.02.018. |
| 19439490 | Background | James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davern TJ, Lee WM. Pharmacokinetics of acetaminophen-protein adducts in adults with acetaminophen overdose and acute liver failure. Drug Metab Dispos. 2009 Aug;37(8):1779-84. doi: 10.1124/dmd.108.026195. Epub 2009 May 13. |
| 21978728 | Background | Jiang H, Hampel H, Prvulovic D, Wallin A, Blennow K, Li R, Shen Y. Elevated CSF levels of TACE activity and soluble TNF receptors in subjects with mild cognitive impairment and patients with Alzheimer's disease. Mol Neurodegener. 2011 Oct 6;6:69. doi: 10.1186/1750-1326-6-69. |
| 31479147 | Background | Kantor ED, Udumyan R, Giovannucci EL, Valdimarsdottir UA, Signorello LB, Montgomery S, Fall K. Association of Blood Marker of Inflammation in Late Adolescence With Premature Mortality. JAMA Pediatr. 2019 Nov 1;173(11):1095-1097. doi: 10.1001/jamapediatrics.2019.2835. |
| 24185570 | Background | Kiresuk TJ, Sherman RE. Goal attainment scaling: A general method for evaluating comprehensive community mental health programs. Community Ment Health J. 1968 Dec;4(6):443-53. doi: 10.1007/BF01530764. |
| 31522977 | Background | Konttinen H, Cabral-da-Silva MEC, Ohtonen S, Wojciechowski S, Shakirzyanova A, Caligola S, Giugno R, Ishchenko Y, Hernandez D, Fazaludeen MF, Eamen S, Budia MG, Fagerlund I, Scoyni F, Korhonen P, Huber N, Haapasalo A, Hewitt AW, Vickers J, Smith GC, Oksanen M, Graff C, Kanninen KM, Lehtonen S, Propson N, Schwartz MP, Pebay A, Koistinaho J, Ooi L, Malm T. PSEN1DeltaE9, APPswe, and APOE4 Confer Disparate Phenotypes in Human iPSC-Derived Microglia. Stem Cell Reports. 2019 Oct 8;13(4):669-683. doi: 10.1016/j.stemcr.2019.08.004. Epub 2019 Sep 12. |
| 23296339 | Background | Liu CC, Liu CC, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013 Feb;9(2):106-18. doi: 10.1038/nrneurol.2012.263. Epub 2013 Jan 8. |
| 34239415 | Background | Lutshumba J, Nikolajczyk BS, Bachstetter AD. Dysregulation of Systemic Immunity in Aging and Dementia. Front Cell Neurosci. 2021 Jun 22;15:652111. doi: 10.3389/fncel.2021.652111. eCollection 2021. |
| 28237313 | Background | MacPherson KP, Sompol P, Kannarkat GT, Chang J, Sniffen L, Wildner ME, Norris CM, Tansey MG. Peripheral administration of the soluble TNF inhibitor XPro1595 modifies brain immune cell profiles, decreases beta-amyloid plaque load, and rescues impaired long-term potentiation in 5xFAD mice. Neurobiol Dis. 2017 Jun;102:81-95. doi: 10.1016/j.nbd.2017.02.010. Epub 2017 Feb 24. |
| 21514250 | Background | McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):263-9. doi: 10.1016/j.jalz.2011.03.005. Epub 2011 Apr 21. |
| 34276428 | Background | McWilliams EC, Barbey FM, Dyer JF, Islam MN, McGuinness B, Murphy B, Nolan H, Passmore P, Rueda-Delgado LM, Buick AR. Feasibility of Repeated Assessment of Cognitive Function in Older Adults Using a Wireless, Mobile, Dry-EEG Headset and Tablet-Based Games. Front Psychiatry. 2021 Jun 25;12:574482. doi: 10.3389/fpsyt.2021.574482. eCollection 2021. |
| 11238292 | Background | Meier-Ewert HK, Ridker PM, Rifai N, Price N, Dinges DF, Mullington JM; New Collective Author. Absence of diurnal variation of C-reactive protein concentrations in healthy human subjects. Clin Chem. 2001 Mar;47(3):426-30. |
| 15793291 | Background | Olleros ML, Guler R, Vesin D, Parapanov R, Marchal G, Martinez-Soria E, Corazza N, Pache JC, Mueller C, Garcia I. Contribution of transmembrane tumor necrosis factor to host defense against Mycobacterium bovis bacillus Calmette-guerin and Mycobacterium tuberculosis infections. Am J Pathol. 2005 Apr;166(4):1109-20. doi: 10.1016/S0002-9440(10)62331-0. |
| 19222369 | Background | Olleros ML, Vesin D, Lambou AF, Janssens JP, Ryffel B, Rose S, Fremond C, Quesniaux VF, Szymkowski DE, Garcia I. Dominant-negative tumor necrosis factor protects from Mycobacterium bovis Bacillus Calmette Guerin (BCG) and endotoxin-induced liver injury without compromising host immunity to BCG and Mycobacterium tuberculosis. J Infect Dis. 2009 Apr 1;199(7):1053-63. doi: 10.1086/597204. |
| 11772511 | Background | Paganelli R, Di Iorio A, Patricelli L, Ripani F, Sparvieri E, Faricelli R, Iarlori C, Porreca E, Di Gioacchino M, Abate G. Proinflammatory cytokines in sera of elderly patients with dementia: levels in vascular injury are higher than those of mild-moderate Alzheimer's disease patients. Exp Gerontol. 2002 Jan-Mar;37(2-3):257-63. doi: 10.1016/s0531-5565(01)00191-7. |
| 29985987 | Background | Parker D, Sloane R, Pieper CF, Hall KS, Kraus VB, Kraus WE, Huebner JL, Ilkayeva OR, Bain JR, Newby LK, Cohen HJ, Morey MC. Age-Related Adverse Inflammatory and Metabolic Changes Begin Early in Adulthood. J Gerontol A Biol Sci Med Sci. 2019 Feb 15;74(3):283-289. doi: 10.1093/gerona/gly121. |
| 22945416 | Background | Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, Haroon E, Miller AH. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry. 2013 Jan;70(1):31-41. doi: 10.1001/2013.jamapsychiatry.4. |
| 21180547 | Background | Siegel CA, Melmed GY. Predicting response to Anti-TNF Agents for the treatment of crohn's disease. Ther Adv Gastroenterol. 2009 Jul;2(4):245-51. doi: 10.1177/1756283X09336364. |
| 14512626 | Background | Steed PM, Tansey MG, Zalevsky J, Zhukovsky EA, Desjarlais JR, Szymkowski DE, Abbott C, Carmichael D, Chan C, Cherry L, Cheung P, Chirino AJ, Chung HH, Doberstein SK, Eivazi A, Filikov AV, Gao SX, Hubert RS, Hwang M, Hyun L, Kashi S, Kim A, Kim E, Kung J, Martinez SP, Muchhal US, Nguyen DH, O'Brien C, O'Keefe D, Singer K, Vafa O, Vielmetter J, Yoder SC, Dahiyat BI. Inactivation of TNF signaling by rationally designed dominant-negative TNF variants. Science. 2003 Sep 26;301(5641):1895-8. doi: 10.1126/science.1081297. |
| 12909295 | Background | Tarkowski E, Liljeroth AM, Minthon L, Tarkowski A, Wallin A, Blennow K. Cerebral pattern of pro- and anti-inflammatory cytokines in dementias. Brain Res Bull. 2003 Aug 15;61(3):255-60. doi: 10.1016/s0361-9230(03)00088-1. |
| Background | Valcarce C, Dunn I, and Burstein A. Inflammatory Biomarkers, Brain Volumetric MRI, FDG-PET Results in Patients with Type 2 Diabetes in Azeligagonphase 3 Trial in Mild Alzheimer's Disease (AD).http://vtvtherapeutics.com/wp-content/uploads/2019/03/AD_PD-presentation_FINAL-March-30-2019_lisbon.pdf |
| 17641054 | Background | Zalevsky J, Secher T, Ezhevsky SA, Janot L, Steed PM, O'Brien C, Eivazi A, Kung J, Nguyen DH, Doberstein SK, Erard F, Ryffel B, Szymkowski DE. Dominant-negative inhibitors of soluble TNF attenuate experimental arthritis without suppressing innate immunity to infection. J Immunol. 2007 Aug 1;179(3):1872-83. doi: 10.4049/jimmunol.179.3.1872. |
| 32171076 | Background | Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11. |
| 10449104 | Background | TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. The Lenercept Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group. Neurology. 1999 Aug 11;53(3):457-65. |
| 28052249 | Background | Gao H, Danzi MC, Choi CS, Taherian M, Dalby-Hansen C, Ellman DG, Madsen PM, Bixby JL, Lemmon VP, Lambertsen KL, Brambilla R. Opposing Functions of Microglial and Macrophagic TNFR2 in the Pathogenesis of Experimental Autoimmune Encephalomyelitis. Cell Rep. 2017 Jan 3;18(1):198-212. doi: 10.1016/j.celrep.2016.11.083. |
| Background | Jaeger, J. H., Clint; Loft, Henrick; Lim, Yen Ying; Aschenbrenner, Andrew; Segerdahl, Marta; Tong, Gary; Mielke, Michelle; Hassenstab, Jason; Stricker, Nikki (2017). The Early AD/ MCI Alzheimer's Cognitive Composite (EMACC): Development & preliminary validation across 4 longitudinal cohorts of a cognitive endpoint for clinical trials in MCI & Early AD stage disease. CTAD. |
| 29760711 | Background | Pegoretti V, Baron W, Laman JD, Eisel ULM. Selective Modulation of TNF-TNFRs Signaling: Insights for Multiple Sclerosis Treatment. Front Immunol. 2018 Apr 30;9:925. doi: 10.3389/fimmu.2018.00925. eCollection 2018. |
| 26117714 | Background | Probert L. TNF and its receptors in the CNS: The essential, the desirable and the deleterious effects. Neuroscience. 2015 Aug 27;302:2-22. doi: 10.1016/j.neuroscience.2015.06.038. Epub 2015 Jun 24. |
| 3116087 | Background | Robbins DS, Shirazi Y, Drysdale BE, Lieberman A, Shin HS, Shin ML. Production of cytotoxic factor for oligodendrocytes by stimulated astrocytes. J Immunol. 1987 Oct 15;139(8):2593-7. |
| 12933918 | Background | Tarkowski E, Andreasen N, Tarkowski A, Blennow K. Intrathecal inflammation precedes development of Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2003 Sep;74(9):1200-5. doi: 10.1136/jnnp.74.9.1200. |
| 29275977 | Background | Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, Correale J, Fazekas F, Filippi M, Freedman MS, Fujihara K, Galetta SL, Hartung HP, Kappos L, Lublin FD, Marrie RA, Miller AE, Miller DH, Montalban X, Mowry EM, Sorensen PS, Tintore M, Traboulsee AL, Trojano M, Uitdehaag BMJ, Vukusic S, Waubant E, Weinshenker BG, Reingold SC, Cohen JA. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018 Feb;17(2):162-173. doi: 10.1016/S1474-4422(17)30470-2. Epub 2017 Dec 21. |
| 32947003 | Background | Zhao A, Li Y, Deng Y; Alzheimer's Disease Neuroimaging Initiative. TNF receptors are associated with tau pathology and conversion to Alzheimer's dementia in subjects with mild cognitive impairment. Neurosci Lett. 2020 Nov 1;738:135392. doi: 10.1016/j.neulet.2020.135392. Epub 2020 Sep 15. |
| 34569707 | Background | Zheng C, Fillmore NR, Ramos-Cejudo J, Brophy M, Osorio R, Gurney ME, Qiu WQ, Au R, Perry G, Dubreuil M, Chen SG, Qi X, Davis PB, Do N, Xu R. Potential long-term effect of tumor necrosis factor inhibitors on dementia risk: A propensity score matched retrospective cohort study in US veterans. Alzheimers Dement. 2022 Jun;18(6):1248-1259. doi: 10.1002/alz.12465. Epub 2021 Sep 27. |
| 32203525 | Background | Zhou M, Xu R, Kaelber DC, Gurney ME. Tumor Necrosis Factor (TNF) blocking agents are associated with lower risk for Alzheimer's disease in patients with rheumatoid arthritis and psoriasis. PLoS One. 2020 Mar 23;15(3):e0229819. doi: 10.1371/journal.pone.0229819. eCollection 2020. |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C540591 | XENP 1595 |
Not provided
Not provided
Not provided