Michael Podeschwa, Oliver Plettenburg, Jochen vom Brocke, Oliver Block, Stephan Adelt, Hans-Josef Altenbach (2003): "Stereoselective synthesis of ''myo''-, ''neo''-, L-''chiro'', D-''chiro'', ''allo''-, ''scyllo''-, and ''epi''-inositol systems via conduritols prepared from ''p''-benzoquinone". ''European Journal of Organic Chemistry'', volume 2003, issue 10, pages 1958-1972. {{doi|10.1002/ejoc.200200572}} Keran Ma, Lynsie A. M. Thomason, JoAnne McLaurin (2012): "''scyllo''-Inositol, preclinical, and clinical data for Alzheimer's disease". Chapter of ''Advances in Pharmacology'', volume 64, pages 177–212. {{doi|10.1016/B978-0-12-394816-8.00006-4}} {{pmid|22840748}} {{isbn|9780123948168}} Daniela Fenili, Mary Brown, Rebecca Rappaport, JoAnne McLaurin (2007): "Properties of ''scyllo''–inositol as a therapeutic treatment of AD-like pathology". ''Journal of Molecular Medicine'', volume 85, pages 603–611. {{doi|10.1007/s00109-007-0156-7}} Alzforum (2019): "[https://www.alzforum.org/therapeutics/elnd005 ELND005]". ''Therapeutics'' section of [https://www.alzforum.org Alzforum website]. Last updated 2019-06-14 [https://web.archive.org/web/20231226004006/https://www.alzforum.org/therapeutics/elnd005?id=130 archived]; accessed 2024-06-31. Alzforum (2014): "[https://www.alzforum.org/news/conference-coverage/new-treatments-alzheimers-behavioral-symptoms-horizon New Treatments for Alzheimer’s Behavioral Symptoms on Horizon]". ''[https://www.alzforum.org/news/conference-coverage/clinical-trials-alzheimers-disease-2014 Clinicat Trials 2014'' section of the [https://www.alzforum.org Alzforum website] dated 2014-12-23, accessed on 2024-06-31. Trevor A Thorpe, C Stasolla, Edward Yeung, Geert-Jan De Klerk, A. Roberts, E.F. George (2008): "The components of plant tissue culture media II. Organic additions, osmotic and pH effects, and support systems". Chapter 4 of ''Plant Propagation by Tissue Culture'', 3rd edition, pages 115–173. {{doi|10.1007/978-1-4020-5005-3_4}} Younghee Yeon (2001): "[https://koreascience.kr/article/JAKO200111920935778.pdf The crystal and molecular structures of ''neo''-inositol and two forms of ''scyllo''-inositol]". ''Korean Journal of Crystallography'', volume 12, issue 3, pages 150-156. S. Salloway, R. Sperling, R. Keren, A.P. Porsteinsson, C.H. van Dyck, P.N. Tariot, S. Gilman, D. Arnold, S. Abushakra, C. Hernandez, G. Crans, E. Liang, G. Quinn, M. Bairu, A. Pastrak, and J.M. Cedarbaum (2011): "A phase 2 randomized trial of ELND005, ''scyllo''-inositol, in mild to moderate Alzheimer disease" (ELND005-AD201 trial). ''Neurology'', volume 77, issue 13, pages 1253-1262. Quote: "The primary efficacy analysis at 78 weeks revealed no significant differences between the treatment groups on the NTB or ADCS-ADL." {{doi|10.1212/WNL.0b013e3182309fa5}} Masaru Yamaoka, Shin Osawa, Tetsuro Morinaga, Shinji Takenaka, Ken-ichi Yoshida (2011): "A cell factory of ''Bacillus subtilis'' engineered for the simple bioconversion of myo-inositol to scyllo-inositol, a potential therapeutic agent for Alzheimer's disease". ''Microbial Cell Factories'', volume 10, article number 69. {{doi|10.1186/1475-2859-10-69}} Daniela Fenili, Keran Ma, JoAnne McLaurin (2010): "''scyllo''-Inositol: A potential therapeutic for Alzheimer's disease". Chapter 5 of ''Emerging Drugs and Targets for Alzheimer's Disease'', Volume 1: ''Beta-Amyloid, Tau Protein and Glucose Metabolism'', pages 94-116 {{doi|10.1039/9781849731065-00094}} Sung-Kee Chung, Yong-Uk Kwon, Young-Tae Chang, Kwang-Hoon Sohn, Jung-Han Shin, Kyu-Hwan Park, Bong-Jin Hong, In-Hee Chung (1999): "Synthesis of all possible regioisomers of scyllo-Inositol phosphate". ''Bioorganic & Medicinal Chemistry'', volume 7, issue 11, pages 2577-2589 {{doi|10.1016/S0968-0896(99)00183-2}} William H. Horner, I.H. Thaker (1968): "The metabolism of ''scyllo''-inositol in ''Streptomyces griseus''". ''Biochimica et Biophysica Acta'' (''BBA''), volume 165, issue 2, pages 306-308 {{doi|10.1016/0304-4165(68)90064-0}} Joseph Bruton, William H. Horner, Gerald A. Russ (1967): "Biosynthesis of streptomycin: IV. Further studies on the biosynthesis of streptidine and ''N''-methyl-''L''-glucosamine". ''Journal of Biological Chemistry'', volume 242, issue 5, 10 march , pages 813-818 {{doi|10.1016/S0021-9258(18)96198-3}} Thomas Michaelis, Gunther Helms, Klaus-Dietmar Merboldt, Wolfgang Hänicke, Harald Bruhn, Jens Frahm (1993): "Identification of ''scyllo''-inositol in proton NMR spectra of human brain in vivo". ''NMR in Biomedicine'', volume 6, issue 1, pages 105-109. {{doi|10.1002/nbm.1940060116}} Hyo Won Lee and Yoshito Kishi (1985): "Synthesis of mono- and unsymmetrical bis-orthoesters of ''scyllo''-inositol". ''Journal of Organic Chemistry'', volume 50, issue 22, pages 4402–4404 {{doi|10.1021/jo00222a046}} Yeong-Hau H. Lien, Thomas Michaelis, Rex A. Moats, Brian D. Ross (1994): "''Scyllo''-inositol depletion in hepatic encephalopathy". ''Life Sciences'', volume 54, issue 20, pages 1507-1512 {{doi|10.1016/0024-3205(94)90018-3}} Tetsuro Morinaga, Hitoshi Ashida and Ken-ichi Yoshida (2010): "Identification of two ''scyllo''-inositol dehydrogenases in ''Bacillus subtilis''". ''Microbiology'', volume 156, issue 5, pages 1538–1546 {{doi|10.1099/mic.0.037499-0}} Tarek Ibrahim, JoAnne McLaurin (2016): "α-Synuclein aggregation, seeding and inhibition by ''scyllo''-inositol". ''Biochemical and Biophysical Research Communications'', volume 469, issue 3, pages 529-534. {{doi|10.1016/j.bbrc.2015.12.043}} Michael S. Rafii, Brian G. Skotko, Mary Ellen McDonough, Margaret Pulsifer, Caseye Evans, Eric Doran, Gabriel Muranevici, Patrick Kesslak, Susan Abushakra, Ira T. Lott, for the ELND005-DS Study Group (2017): "A randomized, double-blind, placebo-controlled, Phase II study of oral ELND005 (''scyllo''-inositol) in young adults with Down syndrome without dementia". ''Journal of Alzheimer's Disease'', volume 58, issue 2, pages 401-411 {{doi|10.3233/JAD-160965}} Abstract: Background: ELND005 (scyllo-Inositol; cyclohexane-1,2,3,4,5,6-hexol) has been evaluated as a potential disease-modifying treatment for Alzheimer’s disease (AD). Individuals with Down syndrome (DS) have an increased risk for developing AD dementia. Objective: To evaluate the safety and tolerability of ELND005 and to determine its pharmacokinetics (PK) and relationship between PK parameters, safety outcome measures, and exploratory efficacy outcome measures in young adults with DS without dementia. Methods: This was a prospective, randomized, double-blind, placebo-controlled, parallel-group, three-arm, multicenter Phase II study of the safety and pharmacokinetics of ELND005 administered orally for 4 weeks (ClinicalTrials.gov NCT01791725). Participants who met study eligibility criteria were randomly assigned in a 2 : 1:1 ratio to receive ELND005 at either 250 mg twice daily (BID) or 250 mg once daily (QD) or matching placebo for 4 weeks. Results: There were no apparent treatment group-related trends on cognitive or behavioral measures and there were no SAEs and no deaths in the study. Overall, mean changes from baseline in clinical laboratory parameters, vital sign measurements, electrocardiogram results, and other physical findings were unremarkable. ELND005 accumulation averaged approximately 2-fold with QD dosing, and 3- to 4-fold with BID dosing. Conclusion: Overall, treatment of adults with DS with ELND005 at both doses was well tolerated, achieved measurable blood levels and demonstrated no safety findings. Further studies will be needed to test efficacy. Lief Skøt, Helge Egsgaard (1984): "Identification of ononitol and O-methyl-''scyllo''-inositol in pea root nodules". ''Planta'', volume 161, pages 32–36. {{doi|10.1007/BF00951457}} Paul Ramp, Alexander Lehnert, Susana Matamouros, Astrid Wirtz, Meike Baumgart, Michael Bott (2021): "Metabolic engineering of ''Corynebacterium glutamicum'' for production of ''scyllo''-inositol, a drug candidate against Alzheimer's disease". ''Metabolic Engineering'', volume 67, pages 173-185 {{doi|10.1016/j.ymben.2021.06.011}} Kosei Tanaka, Ayane Natsume, Shu Ishikawa, Shinji Takenaka, Ken-ichi Yoshida (2017): "A new-generation of ''Bacillus subtilis'' cell factory for further elevated ''scyllo''-inositol production". ''Microbial Cell Factories'', volume 16, article number 67. {{doi|10.1186/s12934-017-0682-0}}, Elizabeth R. Seaquist, Rolf Gruetter (1998): "Identification of a high concentration of ''scyllo''-inositol in the brain of a healthy human subject using ¹H- and ¹³C-NMR". ''Magnetic Resonance in Medicine'', volume 39, issue 2, pages 313-316. {{doi|10.1002/mrm.1910390220}} M. Nozadze, E. Mikautadze, E. Lepsveridze, E. Mikeladze, N. Kuchiashvili, T. Kiguradze, M. Kikvidze, R. Solomonia (2011): "Anticonvulsant activities of myo-inositol and scyllo-inositol on pentylenetetrazol induced seizures". ''Seizure'', Volume 20, Issue 2, March , Pages 173-176 {{doi|10.1016/j.seizure.2010.10.008}} Lana G. Kaiser, Norbert Schuff, Nathan Cashdollar, Michael W. Weiner (2005): "''Scyllo''-inositol in normal aging human brain: ¹H magnetic resonance spectroscopy study at 4 Tesla". ''NMR in Biomedicine'', volume 18, issue 1, pages 51-55. {{doi|10.1002/nbm.927}} (): "". '''', {{doi|}} (): "". '''', {{doi|}} (): "". '''', {{doi|}} (): "". '''', {{doi|}} (): "". '''', {{doi|}} ---------------------------------------------------------------------- The metabolism of scyllo-inositol in Streptomyces griseus scyllo-Inositol, is widely distributed in nature in fish, mammalian urines, rat tissue and plants 1. More recently it has been detected in Streptomyces griseus 2, insects a and mammalian nerve and kidney 4. Although the biological function of scyllo-inositol remains unknown, recent progress has been made in elucidating the metabolism of this cyclitol. POSTERNAK et al. 5 administered 2-14C-labeled myo-inositol and ~4C-labeled scyllo-inositol, to rats and isolated labeled sqvllo-inositol and labeled myo-inositol, respectively, from the carcasses. Administration of [2-14CJmyo-inosose-2 resulted in isotope incorporation into both cyclitols isolated from rat carcass. Based on these findings, myo-inosose-2 was suggested as an intermediate in the interconversion of these cyclitols. SCHOLDA et al. 6 using both z~C-labeled myo-inositol and myo-inosose-2 showed that the plant Calycanthus occidentalis converted myo-inositol to scyllo-inositol, and myo-inosose-2 to both cyclitols. BRUTON, HORNER AND Russ 2 detected interconversion of these inositols by Streptomyces griseus with uniformly l~C-labeled myo-inositol and [aHJscyllo-inositol. CANDY ~ found that fat body extracts of the locust, Schistocerca gregaria, converted uniformly ~4C-labeled myo-inositol to II~C~scyllo-inositol provided NAD + was present. Evidence was also obtained that myo-inosose-2 was converted predominantly to myo-inosit01 when NADH was present and to scyllo-inositol upon NADPH supplementation. Finally, the reactions of the two cyclitols and myoinosose-2 were followed by observing the oxidation and reduction of NAD and NADP spectrophotometrically. Based on these results the following pathway for epimerization was proposed by CANDY3: NAD+ NADP+ "~ myo-inosose-2 ~ ~ scyllo-inositol myo-Inositol .. NADH NADPH No direct evidence for the formation of myo-inosose-2 as an intermediate in the interconversion of myo-inositol and scyllo-inositol was provided by these experiments. It should be noted, however, that myo-inosose-2 is a product of myo-inositol oxidation in Acetobactersuboxydans 7 and Aerobacter aerogenes s and has been detected in mammalian nerve and brain ~. In this communication we report the formation of labeled myo-inosose-2 from either [2-~4Clmyo-inositol or FaH~scyllo-inositol and the conversion of uniformly zaClabeled myo-inosose-2 to both cyclitols by S. griseus.