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A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease
Open accessAbstract
OBJECTIVE: This randomized, double-blind, placebo-controlled, dose-ranging phase 2 study explored safety, efficacy, and biomarker effects of ELND005 (an oral amyloid anti-aggregation agent) in mild to moderate Alzheimer disease (AD). METHODS: A total of 353 patients were randomized to ELND005 (250, 1,000, or 2,000 mg) or placebo twice daily for 78 weeks. Coprimary endpoints were the Neuropsychological Test Battery (NTB) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale. The primary analysis compared 250 mg (n =84) to placebo (n =82) after an imbalance of infections and deaths led to early discontinuation of the 2 higher dose groups. RESULTS: The 250 mg dose demonstrated acceptable safety. The primary efficacy analysis at 78 weeks revealed no significant differences between the treatment groups on the NTB or ADCS-ADL. Brain ventricular volume showed a small but significant increase in the overall 250 mg group (p =0.049). At the 250 mg dose, scyllo-inositol concentrations increased in CSF and brain and CSF Aβx-42 was decreased significantly compared to placebo (p =0.009). CONCLUSIONS: Primary clinical efficacy outcomes were not significant. The safety and CSF biomarker results will guide selection of the optimal dose for future studies, which will target earlier stages of AD. CLASSIFICATION OF EVIDENCE: Due to the small sample sizes, this Class II trial provides insufficient evidence to support or refute a benefit of ELND005.
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“The oral drug, scyllo-inositol is a Aβ42 aggregation inhibitor that was studied in AD subjects (ELND005). A clinical study (phase 2) in patients with AD found no confirmation of ELND005′s clinical benefit, and the study was stopped due to severe toxicity concerns (Salloway et al., 2011).”
From An update on the novel and approved drugs for Alzheimer disease (2022) · cites this paper as Salloway et al., 2011
In the citing paper
“Further development of the agent at a lower dose has not progressed in the last 8 years.50”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [50]
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“A phase 2 clinical trial in patients with AD did not provide evidence to support a clinical benefit of ELND005 while severe toxicity issues (infections) forced the cessation of the study.”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [50]
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“The last Aβ42 aggregation inhibitor which was tested in humans was the oral agent scyllo-inositol (ELND005).”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [50]
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Citations
Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915
The Clinical Dementia Rating (CDR): Current version and scoring rules
Morris, J. C. (1993) · Neurology · doi:10.1212/wnl.43.11.2412-a · Cited by 9,882
The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia
Cummings, J. L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D. A., & Gornbein, J. (1994) · Neurology · doi:10.1212/wnl.44.12.2308 · Cited by 7,568
A New Clinical Scale for the Staging of Dementia
Hughes, C. P., Berg, L., Danziger, W., Coben, L. A., & Martin, R. L. (1982) · British Journal of Psychiatry · doi:10.1192/bjp.140.6.566 · Cited by 7,056
Querfurth, H. W., & LaFerla, F. M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0909142 · Cited by 4,569
A new rating scale for Alzheimer's disease
(1984) · American Journal of Psychiatry · doi:10.1176/ajp.141.11.1356 · Cited by 4,175
Alzheimer's Disease Neuroimaging Initiative (ADNI)
Petersen, R. C., Aisen, P. S., Beckett, L. A., Donohue, M. C., Gamst, A. C., Harvey, D. J., Jack, C. R., Jagust, W. J., Shaw, L. M., Toga, A. W., et al. (2010) · Neurology · doi:10.1212/wnl.0b013e3181cb3e25 · Cited by 2,572
Accurate, Robust, and Automated Longitudinal and Cross-Sectional Brain Change Analysis
Smith, S. M., Zhang, Y., Jenkinson, M., Chen, J. M., Matthews, P. M., Federico, A., & Stefano, N. D. (2002) · NeuroImage · doi:10.1006/nimg.2002.1040 · Cited by 2,013
Shankar, G. M., Bloodgood, B. L., Townsend, M., Walsh, D. M., Selkoe, D. J., & Sabatini, B. L. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4970-06.2007 · Cited by 1,592
Clinical effects of Aβ immunization (AN1792) in patients with AD in an interrupted trial
Gilman, S., Koller, M., Black, R. S., Jenkins, L., Griffith, S. G., Fox, N. C., Eisner, L., Kirby, L., Rovira, M. B., Forette, F., et al. (2005) · Neurology · doi:10.1212/01.wnl.0000159740.16984.3c · Cited by 1,329
Self-citationPathological verification of ischemic score in differentiation of dementias
Rosen, W. G., Terry, R. D., Fuld, P. A., Katzman, R., & Peck, A. (1980) · Annals of Neurology · doi:10.1002/ana.410070516 · Cited by 1,273
An Inventory to Assess Activities of Daily Living for Clinical Trials in Alzheimerʼs Disease
Galasko, D., Bennett, D. A., Sano, M., Ernesto, C., Thomas, R., Grundman, M., & Ferris, S. H. (1997) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199700112-00005 · Cited by 1,198
Galasko, D. R., Bennett, D., Sano, M., Ernesto, C., Thomas, R., Grundman, M., & Ferris, S. H. (1997) · PubMed · Cited by 767
A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease
Salloway, S., Sperling, R., Gilman, S., Fox, N. C., Blennow, K., Raskind, M., Sabbagh, M., Honig, L. S., Doody, R., van Dyck, C. H., et al. (2009) · Neurology · doi:10.1212/wnl.0b013e3181c67808 · Cited by 753
Self-citationLannfelt, L., Blennow, K., Zetterberg, H., Batsman, S., Ames, D., Harrison, J., Masters, C. L., Targum, S., Bush, A. I., Murdoch, R., et al. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70167-4 · Cited by 725
Rinne, J. O., Brooks, D. J., Rossor, M. N., Fox, N. C., Bullock, R., Klunk, W. E., Mathis, C. A., Blennow, K., Barakos, J., Okello, A. A., et al. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70043-0 · Cited by 701
Effects of Aβ immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease
Fox, N. C., Black, R. S., Gilman, S., Rossor, M. N., Griffith, S. G., Jenkins, L., & Koller, M. (2005) · Neurology · doi:10.1212/01.wnl.0000159743.08996.99 · Cited by 550
Self-citationGalasko, D., Chang, L., Motter, R., Clark, C. M., Kaye, J., Knopman, D., Thomas, R., Kholodenko, D., Schenk, D., Lieberburg, I., et al. (1998) · Archives of Neurology · doi:10.1001/archneur.55.7.937 · Cited by 442
Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe
Feldman, H. H., Doody, R. S., Kivipelto, M., Sparks, D. L., Waters, D. D., Jones, R. W., Schwam, E., Schindler, R., Hey-Hadavi, J., DeMicco, D. A., et al. (2010) · Neurology · doi:10.1212/wnl.0b013e3181d6476a · Cited by 438
The role of cerebral amyloid accumulation in common forms of Alzheimer disease
Gandy, S. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25100 · Cited by 407
McLaurin, J., Kierstead, M. E., Brown, M. E., Hawkes, C. A., Lambermon, M. H. L., Phinney, A. L., Darabie, A. A., Cousins, J. E., French, J. E., Lan, M. F., et al. (2006) · Nature Medicine · doi:10.1038/nm1423 · Cited by 373
Genetic dissection of Alzheimer's disease and related dementias: amyloid and its relationship to tau
Hardy, J., Duff, K., Hardy, K. G., Pérez‐Tur, J., & Hutton, M. (1998) · Nature Neuroscience · doi:10.1038/1565 · Cited by 356
Fox, N. C., Cousens, S., Scahill, R. I., Harvey, R. J., & Rossor, M. N. (2000) · Archives of Neurology · doi:10.1001/archneur.57.3.339 · Cited by 356
Alzheimer Disease and Mortality: A 15-Year Epidemiological Study
Ganguli, M., Dodge, H. H., Shen, C., Pandav, R. S., & DeKosky, S. T. (2005) · Archives of Neurology · doi:10.1001/archneur.62.5.779 · Cited by 297
McLaurin, J., Golomb, R., Jurewicz, A., Antel, J. P., & Fraser, P. E. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m906994199 · Cited by 268
Cause of death in patients with dementia disorders
Brunnström, H. R., & Englund, E. M. (2009) · European Journal of Neurology · doi:10.1111/j.1468-1331.2008.02503.x · Cited by 246
Collins, D. L., & Pruessner, J. C. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.04.193 · Cited by 227
A Neuropsychological Test Battery for Use in Alzheimer Disease Clinical Trials
Harrison, J., Minassian, S. L., Jenkins, L., Black, R. S., Koller, M., & Grundman, M. (2007) · Archives of Neurology · doi:10.1001/archneur.64.9.1323 · Cited by 226
Relating neocortical pathology to disability progression in multiple sclerosis using MRI
Chen, J.-T., Narayanan, S., Collins, D., Smith, S. M., Matthews, P., & Arnold, D. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.07.046 · Cited by 169
Orally available compound prevents deficits in memory caused by the Alzheimer amyloid‐β oligomers
Townsend, M., Cleary, J. P., Mehta, T., Hofmeister, J. J., Lesné, S., O‘Hare, E., Walsh, D. M., & Selkoe, D. J. (2006) · Annals of Neurology · doi:10.1002/ana.21051 · Cited by 169
Gauthier, S. G., Aisen, P. S. S., Ferris, S. H., Saumier, D., Duong, A., Haine, D., Garceau, D., Suhy, J., Oh, J., Lau, W. C., et al. (2009) · The journal of nutrition health & aging · doi:10.1007/s12603-009-0106-x · Cited by 136
Properties of scyllo–inositol as a therapeutic treatment of AD-like pathology
Fenili, D., Brown, M., Rappaport, R. V., & McLaurin, J. (2007) · Journal of Molecular Medicine · doi:10.1007/s00109-007-0156-7 · Cited by 136
Smith, S. M., Rao, A. W., Stefano, N. D., Jenkinson, M., Schott, J. M., Matthews, P. M., & Fox, N. C. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.04.035 · Cited by 110
Towards Disease-Modifying Treatment of Alzheimers Disease: Drugs Targeting β -Amyloid
Frisardi, V., Solfrizzi, V., Imbimbo, B. P., Capurso, C. A., D’Introno, A., Colacicco, A. M., Vendemiale, G., Seripa, D., Pilotto, A., Capurso, C. A., et al. (2010) · Current Alzheimer Research · doi:10.2174/156720510790274400 · Cited by 107
Doraiswamy, P. M., Kaiser, L., Bieber, F., & Garman, R. L. (2001) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-200110000-00003 · Cited by 105
CDP-diglyceride:inositol transferase from rat liver. Purification and properties.
Takenawa, T., & Egawa, K. (1977) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)63366-1 · Cited by 99
How Well Do the ADAS-cog and its Subscales Measure Cognitive Dysfunction in Alzheimer’s Disease?
Benge, J., Balsis, S., Geraci, L., Massman, P., & Doody, R. (2009) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000230709 · Cited by 77
Alzheimer's disease therapeutic research: the path forward
Aisen, P. S. S. (2009) · Alzheimer s Research & Therapy · doi:10.1186/alzrt2 · Cited by 59
Scyllo‐inositol in normal aging human brain: 1H magnetic resonance spectroscopy study at 4 Tesla
Kaiser, L. G., Schuff, N. W., Cashdollar, N. M., & Weiner, M. W. (2004) · NMR in Biomedicine · doi:10.1002/nbm.927 · Cited by 48
Garzone, P. D., Koller, M., Pastrak, A., Jhee, S. S., Ereshefsky, L., Moran, S., Cedarbaum, J. M., Xu, V., & Ross, B. D. (2009) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2009.04.526 · Cited by 10
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Scheltens, P., Blennow, K., Breteler, M. M. B., de Strooper, B., Frisoni, G. B., Salloway, S., & Van der Flier, W. M. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01124-1 · Cited by 3,125
Alzheimer Mechanisms and Therapeutic Strategies
Huang, Y., & Mucke, L. (2012) · Cell · doi:10.1016/j.cell.2012.02.040 · Cited by 1,758
Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer's Disease
Doody, R. S., Thomas, R. G., Farlow, M., Iwatsubo, T., Vellas, B., Joffe, S., Kieburtz, K., Raman, R., Sun, X., Aisen, P. S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1312889 · Cited by 1,668
Current and Future Treatments in Alzheimer Disease: An Update
Yiannopoulou, K. G., & Papageorgiou, S. G. (2020) · Journal of Central Nervous System Disease · doi:10.1177/1179573520907397 · Cited by 966
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Panza, F., Lozupone, M., Logroscino, G., & Imbimbo, B. P. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-018-0116-6 · Cited by 965
Metadata
- Authors
- Salloway, S., Sperling, R., Keren, R., Porsteinsson, A. P., van Dyck, C. H., Tariot, P. N., Gilman, S., Arnold, D., Abushakra, S., Hernandez, C., Crans, G., Liang, E., Quinn, G., Bairu, M., Pastrak, A., Cedarbaum, J. M., & For the ELND005-AD201 Investigators
- Affiliations
- Brigham and Women's Hospital (US)
- From the Department of Neurology, Butler Hospital, and Department of Neurology, Alpert Medical School of Brown University (S.S.), Providence, RI; Center for Alzheimer Research and Treatment (R.S.), Brigham and Women's Hospital, Boston, MA; Ontario Shores Centre for Mental Health Sciences (R.K.), Whitby, Canada; Monroe Community Hospital (A.P.P.), University of Rochester Medical Center, Rochester, NY; Departments of Psychiatry and Neurobiology (C.H.v.D.), Yale University School of Medicine, New Haven...
- ORCID
- Venue
- Neurology
- Published
- 2011-09-27
- Volume
- 77
- Issue
- 13
- Pages
- 1253-1262
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3179648
- OpenAlex
- W2119197968
- Cited by
- 258
- References
- 42
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 11 · 2023: 17 · 2022: 18 · 2021: 14 · 2020: 22 · 2019: 17 · 2018: 13 · 2017: 20 · 2016: 22 · 2015: 21 · 2014: 21 · 2013: 24 · 2012: 17
- FWCI
- 14.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Elan
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Keywords
- scyllo-inositol, Alzheimer's disease, amyloid-beta, cerebrospinal fluid biomarkers, activities of daily living, neuropsychological performance, dose-ranging, drug safety
- MeSH terms
- Administration, Oral, Aged, Aged, 80 and over, Alzheimer Disease, Dose-Response Relationship, Drug, Double-Blind Method, Female, Follow-Up Studies, Humans, Inositol, Magnetic Resonance Imaging, Male, Mental Status Schedule, Middle Aged, Peptide Fragments, Platelet Aggregation Inhibitors, Time Factors, Amyloid beta-Peptides, Treatment Outcome, Apolipoprotein E4
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