Chap13 Dokka
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Transcript of Chap13 Dokka
Vesicular Transport
Kartheek Kumar DokkaChapter 13
Vesicular Transport
Budding and Fusion
Clathrin Coated Vesicles
Clathrin Coated Vesicles
SNARES!!
Nerve Cell
How they move!
The Bacteria! The Neurotoxin: Botulinum
Botulinum Alert!
• Purified sub-unit A of the botulinum toxin.• Botox-A is a protease and is known for its property of
cleaving the SNARE proteins.• Allergan targeted the neuro-muscular
junctions to treat “Strabismus” and “Blepharospasm”.
Effect of Botox
• Example of botulinum toxin treatment in a patient with essential blepharospasm.
$$$ for Allergan!
We are…• Syntaxin Ltd. is a newly formed biotechnology company focusing on discovery
and development of new medicines derived from bacterial toxins to treat chronic diseases.
• Hypersecretion of mucus into the airways is an important contributor to morbidity and mortality in many patients with severe chronic lung diseases, such as chronic obstructive pulmonary disorder (COPD), asthma and cystic fibrosis.
• Current treatments for COPD are palliative and do not halt disease progression, and there is no specific treatment for the mucus hypersecretion.
• In patients with COPD, levels of the mucins are increased in the respiratory mucus.• One possibility for inhibiting mucus secretion is to utilize the anti-secretory activity
of proteases of clostridial neurotoxins, targeted to the mucin secreting cells of the airway using Syntaxin's novel recombinant proteins.
What did we do…• Syntaxin explored a number of peptide ligands to
receptors known to be present on mucin secreting cells of the respiratory epithelium, and proteases from serotypes of botulinum neurotoxin known to cleave SNARE proteins found within these cells.
• The target product profile for this programme is a recombinant therapeutic protein that can be administered on an infrequent basis by inhalation to patients with a mucus hypersecretory component to their chronic respiratory condition such as COPD.
• Targeted: A549 cells which are carcinomic human alveolar basal epithelial cells. [Cause excessive production of Mucus!]
• With: Recombinant therapeutic protein “SXN 187” [Recombinaint A-subunit of BoTox.]
What we got…• Effect of SXN187 on
intracellular mucin in A549 cells:
• The level of mucus created by these cells is reduced and mucin was retained inside the treated cells.
• C-Control: Must be Known Mucin Secretion Inhibitor.
• EC-Experimental Control
Through this biotech research & development model Syntaxin aims to develop a family of medicines for chronic disorders where cell secretion is a major contributor to their pathology.
So basically…..• Chronic diseases involving neurotransmitter release can be treated using
botulinum neurotoxins and in the future novel proteins to inhibit the neuron cells.
• The overall status of various products by different companies using this technology in various pathologies:
References!• http://www.unil.ch/webdav/site/ib/shared/Mayer/Mayer.Fig1.jpg• www.zoology.ubc.ca/.../clathrin_pits.htm• www.unil.ch/ib/page9494.html• http://mol-biol4masters.org/Co_and_Post_Translational_Events5-Cellular_Protein
_Traffic_files/image069.jpg• http://www.georgiapainphysicians.com/l2_edu_pharma_mod1_slides.htm• http://biomarker.cdc.go.kr:8080/biomarker/biomarker/3rd_str/3BTAx500.jpg• www.biocarta.com/pathfiles/h_BOTULINPATHWAY.asp• http://www.syntaxin.com/index.php• http://en.wikipedia.org/wiki/A549• http://www.allergan.com/index.htm• http://www.goa-dental-clinic.com/images/botox.jpg• www.plasticsurgeryhumour.com/botox/ [my favorite]