Peer-reviewed Publications

MANY PUBLICATIONS IN PEER-REVIEWED JOURNALS SUPPORT ZIVA’S CLINICAL EFFICACY
AND MECHANISM OF ACTION.

 

The Lysosome as a Regulatory Hub

Roberto Zonchu, Sabatini Lab, Whitehead Institute. “The Secret Power of the Cell’s Waste Bin”. Quanta Magazine

 

Gaucher/Parkinsons

Emily M. Rocha, Briana De Miranda, Laurie H. Sanders. “Alpha-synuclein: Pathology, mitochondrial dysfunction and neuroinflammation in Parkinson’s disease.” Neurobiology of Disease. 2017 April 8.

Kinghorn KJ, Asghari AM, Castillo-Quan JI. “The emerging role of autophagic-lysosomal dysfunction in Gaucher disease and Parkinson’s disease.” Neural Regen Res, 2017 Mar

Elma Aflaki, Wendy Westbroek, and Ellen Sidransky. “The Complicated Relationship
between Gaucher Disease and Parkinsonism: Insights from a Rare Disease.” Neuron 93, February 22, 2017

Pramod K. Mistry, Grisel Lopez, Raphael Schiffmann, Norman W. Barton, Neal J. Weinreb, Ellen Sidransky. “Gaucher disease: Progress and ongoing challenges.” Molecular Genetics and Metabolism. Jan-Feb 2017

Tim E. Moors , Jeroen J. M. Hoozemans, Angela Ingrassia, Tommaso Beccari, Lucilla Parnetti, Marie-Christine Chartier-Harlin and Wilma D. J. van de Berg. “Therapeutic potential of autophagyenhancing agents in Parkinson’s disease” Molecular Neurodegeneration. 2017 Jan 25.

Migdalska-Richards A, Daly L, Bezard E2, Schapira AH. “Ambroxol effects in glucocerebrosidase and α-synuclein transgenic mice.” Ann Neurol. 2016 Nov.

Sanchez-Martinez A, Beavan M, Gegg ME, Chau KY, Whitworth AJ, Schapira AH. “Parkinson disease-linked GBA mutation effects reversed by molecular chaperones in human cell and fly models.” Sci Rep. 2016 Aug 19.

Aflaki E, Borger DK, Moaven N, Stubblefield BK, Lopez GJ, Goldstein DS, Ory DS, Marugan J, Sidransky E.”A New Glucocerebrosidase Chaperone Reduces α-Synuclein and Glycolipid Levels in iPSC-Derived Dopaminergic Neurons from Patients with Gaucher Disease and Parkinsonism.” The Journal of Neuroscience. 2016 Jul. 13.

Aya Narita. “Ambroxol chaperone therapy for neuronopathic Gaucher disease: A pilot study.” Annals of Clinical and Translational Neurology. 2016 Mar. 1

Zywie Summary of Japanese Compassionate Use Study June 2015

Richter F, Fleming SM, Watson M, Lemesre V, Pellegrino L, Ranes B, Zhu C, Mortazavi F, et al. “A GCase Chaperone Improves Motor Function in a Mouse Model of Synucleinopathy.” Neurotherapeutics. 2014 Oct.11.

Sardi SP1, Clarke J, Viel C, Chan M, Tamsett TJ, Treleaven CM, Bu J, Sweet L, Passini MA, Dodge JC, Yu WH, Sidman RL, Cheng SH, Shihabuddin LS. “Augmenting CNS glucocerebrosidase activity as a therapeutic strategy for parkinsonism and other Gaucher-related synucleinopathies.” Proceedings of the National Academy of Sciences of the United States of America 2013 Feb. 26.

Inna Bendikov-Bar, Gali Maor, Mirella Filocamo, Mia Horowitz. “Ambroxol as a pharmacological chaperone for mutant glucocerebrosidase.” Blood Cells, Molecules and Diseases 2012 Oct.

Shachar T1, Lo Bianco C, Recchia A, Wiessner C, Raas-Rothschild A, Futerman AH. “Lysosomal storage disorders and Parkinson’s disease: Gaucher disease and beyond.” Movement Disorders 2011 Aug.1.

Dawson,Ted, Dawson, Valina L. “A Lysosomal Lair for a Pathogenic Protein Pair.” Science Translational Medicine 2011 July 13.

Burrow, Barnes, Grabowski. “Prevalence and management of Gaucher disease.” Dove Press Journal 2011 June 20.

Inna Bendikov-Bar, Idit Ron, Mirella Filocamo, Mia Horowitz. “Characterization of the ERAD process of the L444P mutant glucocerebrosidase variant.” Blood, Cells, Molecules & Diseases 46.1 (2011)

Mylvaganam Jeyakumar, Raymond A. Dwek, Terry D. Butters ,Frances M. Platt. “Storage Solutions:Treating Lysosomal Disorders of the Brain.” Nature Reviews Neuroscience Vol. 6 2005 Sept.

Ron I1, Horowitz M. “ER retention and degradation as the molecular basis underlying Gaucher disease heterogeneity.”Human Molecular Genetics 2005 Aug. 15.

Mazzulli JR1, Xu YH, Sun Y, Knight AL, McLean PJ, Caldwell GA, Sidransky E, Grabowski GA, Krainc D. “Gaucher disease glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies.” Cell 2001 July 8.

 

Parkinsons

Chelsea Caspell-Garcia, Tanya Simuni, Duygu Tosun-Turgut, I-Wei Wu, Yu Zhang, Mike Nalls, Andrew Singleton, Leslie A. Shaw, Ju-Hee Kang, John Q. Trojanowski, Andrew Siderowf, Christopher Coffey, Shirley Lasch, Dag Aarsland, David Burn, Lana M. Chahine, Alberto J. Espay, Eric D. Foster, Keith A. Hawkins, Irene Litvan, Irene Richard, Daniel Weintraub, and the Parkinson’s Progression Markers Initiative (PPMI). “Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease.” PLOS, 2017 May 17

Migdalska-Richards A, Schapira AH. “The relationship between glucocerebrosidase mutations and Parkinson disease.” J Neurochem. 2016 Oct 1

Joseph R. Mazzulli, Friederike Zunke, Taiji Tsunemi, Nicholas J. Toker, Sohee Jeon, Lena F. Burbulla, Samarjit Patnaik, Ellen Sidransky, Juan J. Marugan, Carolyn M. Sue and Dimitri Krainc. “Activation of β-Glucocerebrosidase Reduces Pathological α-Synuclein and Restores Lysosomal Function in Parkinson’s Patient Midbrain Neurons”. Journal of Neuroscience. 2016 Jul. 20

Mazzulli JR, Xu YH, Sun Y, Knight AL, McLean PJ, Caldwell GA, Sidransky E, Grabowski GA, Krainc D. “Gaucher disease glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies.” Cell. 2014 Jul. 8

Roger L. Albin,and William T. Dauer.”Magic shotgun for Parkinson’s disease?” Brain 2014 June 23.

McNeill A1, Magalhaes J, Shen C, Chau KY, Hughes D, Mehta A, Foltynie T, Cooper JM, Abramov AY, Gegg M, Schapira AH. “Ambroxol improves lysosomal biochemistry in glucocerebrosidase mutation-linked Parkinson disease cells.” Brain 2014 May.

Irwin DJ1, Lee VM, Trojanowski JQ. “Parkinson’s disease dementia: convergence of α-synuclein, tau and amyloid-β pathologie.”.Nature Reviews Neuroscience 2013 Sept.

Swan M1, Saunders-Pullman R. “The association between ß-glucocerebrosidase mutations and Parkinsonism.” NIH PA Author Manuscript 2013 Aug.

Schapira, Anthony H.V., Gegg ME. “Glucocerebrosidase in the pathogenesis and treatment of Parkinson disease.” Proc Natl Acad Sci U S A. 2013 Feb. 26.

Sidransky E, Lopez G. “The link between the GBA gene and parkinsonism.” NIH PA Author Manuscript 2012 Nov.

Gegg ME1, Burke D, Heales SJ, Cooper JM, Hardy J, Wood NW, Schapira AH. “Glucocerebrosidase deficiency in substantia nigra of parkinson disease brains.”Annuals of Neurology 2012 Sept.

Goker-Alpan O1, Masdeu JC, Kohn PD, Ianni A, Lopez G, Groden C, Chapman MC, Cropp B, et al. “The neurobiology of glucocerebrosidase-associated parkinsonism: a positron emission tomography study of dopamine synthesis and regional cerebral blood flow.” Brain 2012 Aug.

Yap TL, Gruschus JM, Velayati A, Westbroek W, Goldin E, Moaven N, Sidransky E, Lee JC. “Alpha-synuclein interacts with Glucocerebrosidase providing a molecular link between Parkinson and Gaucher diseases.” J Biol Chem. 2011 Aug. 12

Cullen V1, Sardi SP, Ng J, Xu YH, Sun Y, Tomlinson JJ, Kolodziej P, Kahn I, Saftig P, Woulfe J, Rochet JC, Glicksman MA, Cheng SH, Grabowski GA, Shihabuddin LS, Schlossmacher MG. “Acid β-glucosidase mutants linked to Gaucher disease, Parkinson disease, and Lewy body dementia alter α-synuclein processing.”Annuals of Neurology 2011 June.

Velayati A, Yu WH, Sidransky E. “The role of glucocerebrosidase mutations in Parkinson disease and Lewy body disorders.” Curr Neurol Neurosci Rep. 2010 May 5

Sidransky. “Multicenter analysis of glucocerebrosidase mutations in Parkinson’s disease.” New England Journal of Medicine. 2009 Oct. 22

 

Gaucher

Zimran A1, Altarescu G, Elstein D. “Pilot study using ambroxol as a pharmacological chaperone in type 1 Gaucher disease.” Blood Cells Molecules & Diseases 2013 Feb.

Suzuki, Yoshiyuki. “Chaperone therapy update: Fabry disease, GM1-gangliosidosis and Gaucher disease.” Brain & Development, Official Journal of the Japanese Society of Child Neurology 2012 Dec.

Maegawa GH1, Tropak MB, Buttner JD, Rigat BA, Fuller M, Pandit D, Tang L, Kornhaber GJ, Hamuro Y, Clarke JT, Mahuran DJ. “Identification and characterization of Ambroxol as an enzyme enhancement agent for Gaucher disease.” The Journal of biological chemistry 2009 Aug. 28.

Tropak MB, Kornhaber G, Rigat B, Maegawa G, Buttner J, Blanchard J, et al. “Identification of pharmacological chaperones for Gaucher disease and characterization of their effects on b-Glucocerebrosidase by hydrogen/deuterium exchange mass spectrometry.” ChemBioChem. 2008 Nov. 3:9(16):2650-2662.

Butters, Terry. “Gaucher disease.” Current Opinion in Chemical Biology. 2007:11:412-418.

 

Lewy Bodies

Goldstein DS, Kopin IJ, Sharabi Y. “Catecholamine autotoxicity. Implications for pharmacology and therapeutics of Parkinson disease and related disorders.” Pharmacol Ther. 2014 Dec;144(3):268-82. doi: 10.1016/j.pharmthera.2014.06.006. Epub 2014 Jun 16.

Overk CR, Cartier A, Shaked G, Rockenstein E, Ubhi K, Spencer B, Price DL, Patrick C, Desplats P, Masliah E. “Hippocampal neuronal cells that accumulate α-synuclein fragments are more vulnerable to Aβ oligomer toxicity via mGluR5–implications for dementia with Lewy bodies.” Mol Neurodegener. 2014 May 19;9:18. doi: 10.1186/1750-1326-9-18.

Narita. “Abnormal pupillary light reflex with chromatic pupillometry in Gaucher disease.” Ann Clin Transl Neurol. 2014 Feb;1(2):135-40. doi: 10.1002/acn3.33. Epub 2014 Feb 4.

Wakabayashi K, Tanji K, Mori F, Takahashi H. “The Lewy body in Parkinson’s disease: molecules implicated in the formation and degradation of alpha-synuclein aggregates.” Neuropathology. 2007 Oct;27(5):494-506.

 

Mouse Models

Sanders A, Hemmelgarn H, Melrose HL, Hein L, Fuller M, Clarke LA. “Transgenic mice expressing human glucocerebrosidase variants: utility for the study of Gaucher disease.” Blood Cells Mol Dis. 2013 Aug;51(2):109-15. doi: 10.1016/j.bcmd.2013.03.006. Epub 2013 Apr 30.

 

Supplemental

Mario Malerba & Beatrice Ragnoli. “Ambroxol in the 21st century: pharmacological and clinical update.” Drug Evaluation.

MJFF TherapeuticPipelineProgram-Pre-Proposal -Spring 2015

MJFF-ambroxol_12-09-2014

GCaseModulators 2014

Vyas et al. Drug Discovery Today 2014 – Nanotechnology

Luan Z, Li L, Higaki K, Nanba E, Suzuki Y, Ohno K. “The chaperone activity and toxicity of ambroxol on Gaucher cells and normal mice.” Brain Dev. 2013 Apr;35(4):317-22. doi: 10.1016/j.braindev.2012.05.008. Epub 2012 Jun 7.

PHMT-12499-prevalence-and-management-of-gaucher-disease_062011

Malerba & Ragnoli_p1121_highlighted 2008

Paper_In_Vitro_Release_Kinetics_2008

Sustained release ambroxol using eudragit 2006