Solanezumab

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Solanezumab?
Monoclonal antibody
Type Whole antibody
Source Humanized
Target Beta amyloid
Clinical data
  • Investigational
Identifiers
955085-14-0 N
None
UNII 5D6PWO0333 YesY
KEGG D10058 N
Chemical data
Formula C6396H9922N1712O1996S42
144.1 kDa
 N (what is this?)  (verify)

Solanezumab (proposed INN) is a monoclonal antibody being investigated by Eli Lilly as a neuroprotector[1] for patients with Alzheimer's disease.[2][3]

Solanezumab, or sola, binds the amyloid-β peptides that aggregate and form plaques in the brain that are an early pathological feature of Alzheimer's disease.[4] Sola binds the central epitope of monomeric amyloid-β, KLVFFAD, (PDB ID 4XXD[5]) with picomolar affinity.[6] This epitope is known as the nucleation site for Aβ oligomerization, and it is these oligomers of Aβ that are thought to be toxic to neurons.

2012 results of the EXPEDITION 1 & 2 phase 3 clinical trials were only mildly encouraging.[7][8][9] but were said to be the "first evidence that targeting the amyloid cascade can slow the progression of disease.”[10]

References[edit]

  1. ^ International Nonproprietary Names for Pharmaceutical Substances (INN, prepublication copy), World Health Organization.
  2. ^ Clinical trial number NCT00749216 for "Solanezumab Safety Study in Japanese Patients With Alzheimer's Disease" at ClinicalTrials.gov
  3. ^ Clinical trial number NCT00905372 for "Effect of LY2062430 on the Progression of Alzheimer's Disease (EXPEDITION)" at ClinicalTrials.gov
  4. ^ Villemagne, Victor L; Burnham, Samantha; Bourgeat, Pierrick; Brown, Belinda; Ellis, Kathryn A; Salvado, Olivier; Szoeke, Cassandra; MacAulay, S Lance; Martins, Ralph; Maruff, Paul; Ames, David; Rowe, Christopher C; Masters, Colin L; Australian Imaging Biomarkers Lifestyle (AIBL) Research Group (2013). "Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: A prospective cohort study". The Lancet Neurology 12 (4): 357–67. doi:10.1016/S1474-4422(13)70044-9. PMID 23477989. 
  5. ^ Crespi, Gabriela A. N.; Hermans, Stefan J.; Parker, Michael W.; Miles, Luke A. (2015). "Molecular basis for mid-region amyloid-β capture by leading Alzheimer's disease immunotherapies". Scientific Reports 5: 9649. doi:10.1038/srep09649. PMID 25880481. 
  6. ^ Watt, Andrew D.; Crespi, Gabriela A. N.; Down, Russell A.; Ascher, David B.; Gunn, Adam; Perez, Keyla A.; McLean, Catriona A.; Villemagne, Victor L.; Parker, Michael W.; Barnham, Kevin J.; Miles, Luke A. (2014). "Do current therapeutic anti-Aβ antibodies for Alzheimer's disease engage the target?". Acta Neuropathologica 127 (6): 803–10. doi:10.1007/s00401-014-1290-2. PMID 24803227. 
  7. ^ "Lilly's Solanezumab Slows Down Alzheimer's Progression". 9 Oct 2012. 
  8. ^ Solanezumab Did it actually work[self-published source?]
  9. ^ "Eli Lilly’s solanezumab faces grim prospects of attaining conditional FDA approval in mild Alzheimer’s". 4 Sep 2012. 
  10. ^ "ALZHEIMER'S DRUG SLOWS MEMORY LOSS BY ONE THIRD". 10 Oct 2012.