Peer-reviewed Publications

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

Alzheimer

The Lysosome as a Regulatory Hub

Swetha Gowrishankar, Yumei Wu, and Shawn M. Ferguson. “Impaired JIP3-dependent axonal lysosome transport promotes amyloid plaque pathology”. The Rockefeller University Press, J. Cell Biol.

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

Gaucher/Parkinsons

Danijela Petkovi
c Ramadza, Marija Zekusic, Tamara Zigman, Ana Skaricic, Ana Bogdanic, Gordana Mustac, Katarina Bosnjak-NaC, David Ozretic, Kousaku Ohno, Ksenija Fumic, Ivo Baric. “Early initiation of ambroxol treatment diminishes neurological manifestations of type 3 Gaucher disease: A long-term outcome of two siblings.” European Journal of Paediatric Neurology. 24 March 2021.

Majdolen Istaiti, Shoshana Revel-Vilk, Michal Becker-Cohen, Tama Dinur, Uma Ramaswami, Daniela Castillo-Garcia, Magdalena Ceron-Rodriguez, Alicia Chan, Predrag Rodic, Radka Stefanova Tincheva, Walla Al-Hertani, Beom Hee Lee, Chia-Feng Yang, Beata Kiec-Wilk, Agata Fiumara, Barbara Rubio, Ari Zimran. “Upgrading the evidence for the use of ambroxol in Gaucher disease and GBA related Parkinson: Investigator initiated registry based on real life data” Wiley. 9 February 2021.

Zunke F, Moise AC, Belur NR, Gelyana E, Stojkovska I, Dzaferbegovic H, Toker NJ, Jeon S, Fredriksen K, Mazzulli JR. “Reversible Conformational Conversion of α-Synuclein into Toxic Assemblies by Glucosylceramide.” Neuron. 2017 Dec 20.

Anna Migdalska‐Richards, Wai Kin D. Ko, Qin Li, Erwan Bezard, and Anthony H. V. Schapira. “Oral ambroxol increases brain glucocerebrosidase activity in a nonhuman primate”. Synapse. 2017 Jul.

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.

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

Parkinsons

Kenny Walter. “Ambroxol Shows Potential as a Parkinson Disease Drug”. www.mdmag.com, January 16, 2020.

Avenali M, Toffoli M, Mullin S, McNeil A, Hughes D A, Mehta A, Blandini F, Schapira A H V. Evolution of prodromal parkinsonian features in a cohort of GBA mutation-positive individuals: a 6-year longitudinal study. J Neurol Neurosurg Psychiatry 2019 90 1091-1097.

Mullin S, Beavan M, Bestwick J, McNeil A, Proukakis C, Cox T, Hughes D, Mehta A, Zetterberg H, Schapira AHV. Evolution and Clustering of Prodromal Parkinsonian Features in GBA1 Carriers. Movement Disorders 34(9):1365-1373 (2019).

Sardi SP, Simuni T. New Era in disease modification in Parkinson’s disease: Review of genetically targeted therapeutics. Parkinsonism and Related Disorders 59:32-38 (2019).

C. R. A. Silveira, J. MacKinley, K. Coleman, Z. Li, E. Finger, R. Bartha, S. A. Morrow, J. Wells, M. Borrie, R. G. Tirona, C. A. Rupar, G. Zou, R. A. Hegele, D. Mahuran, P. MacDonald, M. E. Jenkins, M. Jog, and S. H. Pasternakcorresponding. “Ambroxol as a novel disease-modifying treatment for Parkinson’s disease dementia: protocol for a single-centre, randomized, double-blind, placebo-controlled trial.” BMC Neurol, 2019 Feb 9.

Gatto EM., Da Prat G., Etcheverry JL., Drelichman G., Cesarini M. “Parkinsonisms and Glucocerebrosidase Deficiency: A Comprehensive Review for Molecular and Cellular Mechanism of Glucocerebrosidase Deficiency.” Brain Sci. 2019 Feb.

Gegg ME, Schapira AHV. The role of glucocerebrosidase in Parkinson disease pathogenesis. FEBS Journal. 285, 3591-3600 (2018).

Fabio Blandini, MD, Roberto Cilia, MD, Silvia Cerri, PhD, Gianni Pezzoli, MD, Anthony H.V. Schapira, MD, Stephen Mullin, PhD, and José L. Lanciego, MD, PhD. “Glucocerebrosidase Mutations and Synucleinopathies: Toward a Model of Precision Medicine”. Wiley Online Library, 1 November 2018.

Akanksha Mishra, Lalit Pratap Chandravanshi, Surendra Kumar Trigun, Sairam Krishnamurthy. “Ambroxol modulates 6-Hydroxydopamine-induced temporal reduction in Glucocerebrosidase (GCase) enzymatic activity and Parkinson’s disease symptoms”. Biochemical Pharmacology, 20 July 2018

Tim E. Moors, Silvia Paciotti, Angela Ingrassia, Marialuisa Quadri, Guido Breedveld, Anna Tasegian, Davide Chiasserini, Paolo Eusebi, Gonzalo Duran-Pacheco, Thomas Kremer, Paolo Calabresi, Vincenzo Bonifati, Lucilla Parnetti, Tommaso Beccari, Wilma D. J. van de Berg. “Characterization of Brain Lysosomal Activities in GBA-Related and Sporadic Parkinson’s Disease and Dementia with Lewy Bodies”. Molecular Neurobiology, 17 April 2018.

J. Magalhaes, M. E. Gegg, A. Migdalska-Richards, and A. H. Schapira. “Effects of ambroxol on the autophagy-lysosome pathway and mitochondria in primary cortical neurons”. Sci Rep. 2018 Jan 23.

Seung Pil Yun, Donghoon Kim, Sangjune Kim, SangMin Kim, Senthilkumar S. Karuppagounder, Seung-Hwan Kwon, Saebom Lee, Tae-In Kam, Suhyun Lee, Sangwoo Ham, Jae Hong Park, Valina L. Dawson, Ted M. Dawson, Yunjong Lee and Han Seok Ko. “α-Synuclein accumulation and GBA deficiency due to L444P GBA mutation contributes to MPTP-induced parkinsonism”. Mol Neurodegener. 2018 Jan 8.

Lucilla Parnetti, MD, PhD, Silvia Paciotti, PhD, Paolo Eusebi, PhD, Andrea Dardis, PhD, Stefania Zampieri, PhD, Davide Chiasserini, PhD, Anna Tasegian, PhD, Nicola Tambasco, MD, PhD, Bruno Bembi, MD, Paolo Calabresi, MD, and Tommaso Beccari, PhD. “Effects of ambroxol on the autophagy-lysosome pathway and mitochondria in primary cortical neurons”. Movement Disorders. 2017 #10.

Yumiko V. Taguchi, Jun Liu, Jiapeng Ruan, Joshua Pacheco, Xiaokui Zhang, Justin Abbasi, Joan Keutzer, Pramod K. Mistry, and Sreeganga S. Chandra. “Glucosylsphingosine Promotes α-Synuclein Pathology in Mutant GBA-Associated Parkinson’s Disease”. Neurobiology of Disease. October 4, 2017.

Marie Y. Davis, Catherine O. Johnson, James B. Leverenz, Daniel Weintraub, John Q. Trojanowski, Alice Chen-Plotkin, Vivianna M. Van Deerlin, Joseph F. Quinn, Kathryn A. Chung, Amie L. Peterson-Hiller, Liana S. Rosenthal, Ted M. Dawson, Marilyn S. Albert, Jennifer G. Goldman, Glenn T. Stebbins, Bryan Bernard, Zbigniew K. Wszolek, Owen A. Ross, Dennis W. Dickson, David Eidelberg, Paul J. Mattis, Martin Niethammer, Dora Yearout, Shu-Ching Hu, Brenna A. Cholerton, Megan Smith, Ignacio F. Mata, Thomas J. Montine, Karen L. Edwards, and Cyrus P. Zabetian. “Association of GBA Mutations and the E326K Polymorphism With Motor and Cognitive Progression in Parkinson Disease”. JAMA Neurol. 2017 October 01.

Frida Loria, Jessica Y. Vargas, Luc Bousset, Sylvie Syan, Audrey Salles, Ronald Melki, Chiara Zurzolo. “α-Synuclein transfer between neurons and astrocytes indicates that astrocytes play a role in degradation rather than in spreading”. Acta Neuropathologica. 19 July 2017

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

Grace O’Regana, Ruth-Mary deSouzaa, Roberta Balestrinob and Anthony H. Schapira. “Glucocerebrosidase Mutations in Parkinson Disease.” Journal of Parkinson’s Disease. 28 April 2017.

Byron Creese, Emily Bell, Iskandar Johar, Paul Francis, Clive Ballard, Dag Aarsland. “Glucocerebrosidase mutations and neuropsychiatric phenotypes in Parkinson’s disease and Lewy body dementias: Review and meta-analyses”. Wiley, 20 April 2017

Shi-Yu Yang, Michelle Beavan, Kai-Yin Chau, Jan-Willem Taanman, and Anthony H.V. Schapira. “A Human Neural Crest Stem Cell-Derived Dopaminergic Neuronal Model Recapitulates Biochemical Abnormalities in GBA1 Mutation Carriers.” Stem Cell Reports. March 14, 2017.

Senkevich K.A., Miliukhina I.V., Beletskaia M.V., Gracheva E.V., Kudrevetykh A.V., Nikolaev M.A., Emelyanov A.K., Kopytova A.E., Timofeeva A.A., Yakimovskii A.E., Pchelina S.N. “The clinical features of Parkinson’s dicease in patiants with mutations and polymorphic varients of GBA gene”. Zh Nevrol Psikhiatr Im S.S. Korsakova. 2017.

Albert A. Davisa, Kristin M. Andruska, Bruno A. Benitez, Brad A. Racette, Joel S. Perlmuttera and Carlos Cruchaga. “Variants in GBA, SNCA, and MAPT Influence Parkinson Disease Risk, Age at Onset, and Progression”. Neurobiol Aging. 2017 January 01.

Ignacio F. Mata, James B. Leverenz, Daniel Weintraub, John Q. Trojanowski, Alice Chen-Plotkin, Vivianna M. Van Deerlin, Beate Ritz, Rebecca Rausch, Stewart A. Factor, Cathy WoodSiverio, Joseph F. Quinn, Kathryn A. Chung, Amie L. PetersonHiller, Jennifer G. Goldman, Glenn T. Stebbins, Bryan Bernard, Alberto J. Espay, Fredy J. Revilla, Johnna Devoto, Liana S. Rosenthal, Ted M. Dawson, Marilyn S. Albert, Debby Tsuang, Haley Huston, Dora Yearout, Shu-Ching Hu, Brenna. “GBA variants are associated with a distinct pattern of cognitive deficits in Parkinson disease”. HHS Public Access. 2017 January 01.

Ambroxol – Safety & Mechanism

Kim YM, Yum MS, Heo SH, Kim T, Jin HK, Bae JS, Seo GH, Oh A, Yoon HM, Lim HT, Kim HW, Ko TS, Lim HS, Osborn MJ, Tolar J, Cozma C, Rolfs A, Zimran A, Lee BH, Yoo HW. “Pharmacologic properties of high-dose ambroxol in four patients with Gaucher disease and myoclonic epilepsy.” J Med Genet. 2020 Feb

Mullin, S., Smith, L. Lee. K., et al. Ambroxol for the Treatment of Patients With Parkinson Disease With and Without Glucocerebrosidase Gene Mutations A Nonrandomized, Noncontrolled Trial. JAMA Neurol. January 13, 2020

Mullin S, Hughes D, Mehta A, Schapira AHV. Neurological effects of glucocerebrosidase gene mutations. Eur J Neurol. March 26, 2019;26(3):388-e29.

Schirinzi T, Sancesario GM, Di Lazzaro G, et al. CSF α-synuclein inversely correlates with non-motor symptoms in a cohort of PD patients. Parkinsonism Relat Disord. April 6, 2019;61:203-206.

Do, J., Mckinney, C., Sharma, P. and Sidransky, E. Glucocerebrosidase and its relevance to Parkinson disease. Molecular Neurodegeneration volume 14, Article number: 36 (2019)

Balestrino R, Schapira AHV. Glucocerebrosidase and Parkinson Disease: Molecular, Clinical, and Therapeutic Implications. Neuroscientist. 2018 Oct;24(5):540-559.

Foltynie, T. and Langston, W. Therapies to Slow, Stop, or Reverse Parkinson’s Disease. Journal of Parkinson’s Disease 8 (2018) S115–S121

Billingsley, K. J., Bandres-Ciga, S., Saez-Atienzar, S. & Singleton, A. B. Genetic risk factors in Parkinson’s disease. Cell Tissue Res. 373, 9–20 (2018).

Chen, H. & Ritz, B. The Search for Environmental Causes of Parkinson’s Disease: Moving Forward. J Parkinsons Dis 8, S9–S17 (2018).

Stojkovska, I., Krainc, D. & Mazzulli, J. R. Molecular mechanisms of α-synuclein and GBA1 in Parkinson’s disease. Cell Tissue Res. 373, 51–60 (2018).

Marras, C. et al. Prevalence of Parkinson’s disease across North America. NPJ Parkinsons Dis 4, 21 (2018).

Ivanova, M. M., Changsila, E., Turgut, A. & Goker-Alpan, O. Individualized screening for chaperone activity in Gaucher disease using multiple patient derived primary cell lines. Am J Transl Res 10, 3750–3761 (2018).

Alejandro G Gonzalez Garay, Ludovic Reveiz, Liliana Velasco Hidalgo, Cecilia Solis Galicia. “Ambroxol for women at risk of preterm birth for preventing neonatal respiratory distress syndrome.” Cochrane Database Syst Rev. 2014 Oct 31

Molina, G., Holguin, E. & Teran, E. Oral ambroxol supplement in pregnant women induces fetal lung maturation. Am. J. Obstet. Gynecol. 191, 2177; author reply 2178 (2004).

Laoag-Fernandez JB, Fernandez AM, Maruo T. “Antenatal use of ambroxol for the prevention of infant respiratory distress syndrome.” J Obstet Gynaecol Res. 2000 Aug

Schmalisch G, Wauer RR, Böhme B. “Effect of early ambroxol treatment on lung functions in mechanically ventilated preterm newborns who subsequently developed a bronchopulmonary dysplasia (BPD).” Respir Med. 2000 Apr

Schmalisch, G., Wauer, R. R. & Böhme, B. Changes in pulmonary function in preterm infants recovering from RDS following early treatment with ambroxol: results of a randomized trial. Pediatr. Pulmonol. 27, 104–112 (1999).

Wolff F, Ponnath H, Wiest W. “[Induction of fetal lung maturation using ambroxol and betamethasone. Results of an open multicenter study].” Geburtshilfe Frauenheilkd. 1987 Jan