Solanezumab hope for Alzheimer's Disease

Solanezumab Hope for Alzheimer's Disease?

This article is dedicated to all the caretakers of Alzheimer's disease patients coping with and seeking support, solutions and new treatments.

Video, Image insertion remains uncompleted.

This interactive multimedia article shares several common sections :

Background information about Alzheimer's disease, market projections, images, video, existing drugs and future drugs in R&D. Analysis of the Alzheimer's disease market and forecast for peak sales of bapineuzumab is valid for Solanezumab as well.

Bapineuzumab (Pfizer, J&J, Elan) Review http://knol.google.com/k/krishan-maggon/bapineuzumab-pfizer-j-j-elan-review/3fy5eowy8suq3/119#

For Monoclonal Antibodies, existing blockbuster drugs and potential innovative breakthrough drugs in R&D, please consult

Monoclonal Antibodies Gold Rush http://knol.google.com/k/krishan-maggon/monoclonal-antibodies-gold-rush/3fy5eowy8suq3/126#

Nomenclature Prefix Sub stem A Sub stem B Suffix common

Sola ne zu mab

Innovator choice neuro humanized monoclonal antibody

Solanezumab is a humanized monoclonal antibody for neurological disease.

Solanezumab (Lilly) is a rival mAbs to Bapineuzumab in Alzheimer's Disease Phase III trials. However results of Phase I and II studies are published and reviewed here. Most of the information about the drug is based on press releases from Lilly and abstracts presented at AD conferences and meetings.

Alzheimer's disease

Introduction

Stages of Alzheimer's disease cognitive testing Treatment of Alzheimer's DiseaseLink title New drugs in R&D About Solanezumab Solanezumab is a humanized mAbs for passive immunotherapy of AD and targets N terminus of the beta amyloid protein, one of the factor involved in disease pathogenesis. Alzheimer's disease theory suggests that amyloid beta clumps together and eventually kills brain cells. Solanezumab binds specifically to soluble amyloid beta and thereby may draw the peptide away from the brain through the blood. In short-term clinical studies, solanezumab appeared to have dose-dependent effects on amyloid beta in blood and cerebrospinal fluid. The clinical studies to date have been too short to evaluate any potential delay in the progress of Alzheimer's disease. To date, the only side effect experienced in clinical studies that appeared to be associated with solanezumab treatment has been mild chills consistent with an infusion reaction; other side effects reported in the Phase II study include nausea, vomiting, headache, back pain, and cough. For a more complete listing of potential side effects, prospective clinical trial participants should refer to the informed consent document. Phase I studies LY2062430 (solanezumab) is a humanized monoclonal antibody being studied as a putative disease-modifying treatment of AD. It was given to 19 subjects with mild to moderate AD. Single doses of solanezumab using 0.5, 1.5, 4.0, and 10.0 mg/kg were administered. Safety assessments included gadolinium-enhanced magnetic resonance imaging (MRI) of the brain and cerebrospinal fluid (CSF) analyses at baseline and 21 days after dosing. Plasma and CSF concentrations of solanezumab and amyloid beta (Abeta) and cognitive evaluations were obtained. Administration of solanezumab was generally well tolerated except that mild self-limited symptoms consistent with infusion reactions occurred for 2 of 4 subjects given 10 mg/kg. No evidence of meningoencephalitis, microhemorrhage, or vasogenic edema was present based on magnetic resonance image and CSF analyses. A substantial dose-dependent increase in total (bound plus unbound) Abeta was demonstrated in plasma; CSF total Abeta also increased. No changes in cognitive scores occurred. CONCLUSIONS: A single dose of solanezumab was generally well tolerated, although infusion reactions similar to those seen with administration of other proteins may occur with higher doses. A dose-dependent change in plasma and CSF Abeta was observed, although changes in cognitive scores were not noted. .PMID: 20375655 Clinical trials Bapineuzumab Clinical Studies Ongoing Rank Status Study 1 Completed Solanezumab Safety Study in Japanese Patients With Alzheimer's Disease Condition: Alzheimer's Disease Intervention: Drug: Solanezumab 2 Recruiting Effect of LY2062430 on the Progression of Alzheimer's Disease Condition: Alzheimer's Disease Interventions: Drug: LY2062430; Drug: Placebo 3 Recruiting Effect of LY2062430 on the Progression of Alzheimer's Disease Condition: Alzheimer's Disease Interventions: Drug: LY2062430; Drug: Placebo References ELISA-based measurement of plasma total Aβ1-40 and Aβ1-42, and CSF total and free Aβ1-40 and Aβ1-42 in the presence of solanezumab, a mid-domain anti-A beta antibody Alzheimer's and Dementia, Volume 5, Issue 4, Supplement 1, July 2009, Page P133 Robert A. Dean, Ronald DeMattos, Valentina Gelfanova, John Hale, Richard Lachno, Margret Racke, Jayne Talbot, Eric Siemers Identification, characterization, and comparison of amino-terminally truncated Aβ42 peptides in Alzheimer's disease brain tissue and in plasma from Alzheimer's patients receiving solanezumab immunotherapy treatment Alzheimer's and Dementia, Volume 5, Issue 4, Supplement 1, July 2009, Pages P156-P157 Ronald B. DeMattos, Margaret M. Racke, Valentina Gelfanova, Beth Forster, Michael D. Knierman, Matthew T. Bryan, John E. Hale, Robert A. Dean, Steven M. Paul, Eric R. Siemers Drug development for Alzheimer's disease: Where are we now and where are we headed? The American Journal of Geriatric Pharmacotherapy, Volume 7, Issue 3, June 2009, Pages 167-185 Marwan N. Sabbagh Measurement of cerebrospinal fluid total tau and phospho-tau in phase 2 trials of therapies targeting Aβ Alzheimer's and Dementia, Volume 5, Issue 4, Supplement 1, July 2009, Page P258 Eric R. Siemers, Robert A. Dean, D.R. Lachno, Joseph J. Zajac, Gopalan Sethuraman, Ronald B. DeMattos, Patrick C. May Biochemical biomarkers as endpoints in clinical trials: Applications in Phase 1, 2 and 3 studies Alzheimer's and Dementia, Volume 5, Issue 4, Supplement 1, July 2009, Page P95 Eric Siemers Rapid Cerebral Amyloid Binding by Aβ Antibodies Infused into β-Amyloid Precursor Protein Transgenic Mice Biological Psychiatry, In Press, Corrected Proof, Available online 31 March 2010 David T. Winkler, Dorothee Abramowski, Simone Danner, Mauro Zurini, Paolo Paganetti, Markus Tolnay, Matthias Staufenbiel Aβ immunotherapy: Translation of preclinical biomarkers into the clinic Neuroscience Research, Volume 65, Supplement 1, 2009, Page S4 Ronald DeMattos Siemers ER, Friedrich S, Dean RA, Gonzales CR, Farlow MR, Paul SM, Demattos RB. Safety and changes in plasma and cerebrospinal fluid amyloid beta after a single administration of an amyloid beta monoclonal antibody in subjects with Alzheimer disease. Clin Neuropharmacol. 2010 Mar-Apr;33(2):67-73. Siemers ER, Dean RA, Friedrich S, Ferguson-Sells L, Gonzales C, Farlow MR, May PC.Safety, tolerability, and effects on plasma and cerebrospinal fluid amyloid-beta after inhibition of gamma-secretase. Clin Neuropharmacol. 2007 Nov-Dec;30(6):317-25. Fleisher AS, Raman R, Siemers ER, Becerra L, Clark CM, Dean RA, Farlow MR, Galvin JE, Peskind ER, Quinn JF, Sherzai A, Sowell BB, Aisen PS, Thal LJ. Phase 2 safety trial targeting amyloid beta production with a gamma-secretase inhibitor in Alzheimer disease. Arch Neurol. 2008 Aug;65(8):1031-8. Imbimbo BP. Therapeutic potential of gamma-secretase inhibitors and modulators. Curr Top Med Chem. 2008;8(1):54-61.[[Category:|Category:]][[Category:|Category:]][[Category:|Category:]]