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- References on Cone shells
- List of Journals on the web
- Books on Cone shells
- Bibliography on Australian Shells - Queensland Museum
- Search abebooks.com for CONIDAE or Conus or cone shell in the Title [Press "Start Search"]
- Search the database using the NCBI Entrez Browser
- Search the database for Conus using the New Entrez Nucleotide Search
- Search Felix Lorenz's Checklist of Conidae, based on Röckel, Korn and Kohn (Manual of the Living Conidae, Hemmen Verlag) and his personal observations.
- Link here to Amos' WWW Links page providing an extensive compilation of links to information sources for life scientists with an interest in biological macromolecules. Extensive listings of proteomics resources and companies.
Link here to
SDPMOD: an automated comparative modeling server for small disulfide-bonded proteins (e.g. conotoxin PnIA). Also: Full free-text article about SDPMOD on PubMedCentral
- Link here to the revised and extended 2nd edition of "GastroClass" on the Natural History Museum's website. This resource provides a framework for non-systematists charged with organising gastropods into a usable order.
- Link here to Conotoxin patents and the IBM Patent Server.
- Link here to news update page on Genetics
- Link here to news update page on BBC Science & Technology
- Link here to full complete alphabetized list of all the Conus peptides currently in the Protein Information Resource (PIR).
- Link here to European BioInformatics Institute entry for Conotoxin
- Link here to Pfam entry for Conotoxin. [Pfam is a large collection of multiple sequence alignments and hidden Markov models covering many common protein families]
- Query the Protein Data Bank (PDB) for "conotoxin" structures.
- News of new CONIDAE species
- Commercial development of cone shell venom drugs:
- Elan Corporation, plc (Elan):
- Elan filed a Marketing Authorisation Application (“MAA”) for Prialt™ (Ziconotide) - for treatment of severe chronic pain, in May 2003. The EMEA has accepted the file for review. On June 12, 2003, Elan paid $196.4 million to Pharma Operating in return for the acquisition by Elan of the Pharma Operating royalty rights with respect to Prialt™ (and Sonata). Product revenue for the pain portfolio was strong showing an increase of 34% to $18.2 million in the second quarter of 2003 from $13.6 million in the second quarter of 2002. Historical supply issues that had hindered growth have mostly been resolved and a more favourable supply situation is expected for the remainder of 2003. Efforts are progressing towards making a second quarter 2003 MAA for Prialt in Europe. The final Phase III trial for Prialt required for U.S. submission has recruited patients and Elan expect to file the NDA around year-end. The FDA has granted approval for a treatment IND program, which will follow the completion of enrollment for the current Phase III trial. The Phase III trial for Prialt in patients with severe pain is fully enrolled. Elan expects to file with the FDA a New Drug Application ("NDA") for Prialt in the first quarter of 2004.
Source: Elan second quarter 2003 financial results, Webcast presentations and Press Releases. Download Printer-friendly pdf about Prialt here.
STOP PRESS: see Press Release 7 Jan. 2004 and scientific findings in an article by Staats et al in Journal of the American Medical Association, JAMA 291: 63-70, Jan. 7, 2004. [See- Comment in: JAMA. 2004 Oct 13;292(14):1681; JAMA. 2004 Oct 13;292(14):1681-2; author reply 1682; JAMA. 2004 Oct 13;292(14):1745-6].
- Medscape Medical News "Intrathecal Ziconotide Effective In Treating Pain from Cancer or AIDS", by Laurie Barclay, MD., Jan. 6, 2004
- See also Elan's Former Neurex Product, Prialt, Hits Phase III Endpoint By Cormac Sheridan, 14 January 2004. In this report David Marshall, analyst at NCB Stockbrokers in Dublin, is reported as saying "the company's most immediate target is likely to be that fraction of patients using intrathecal pumps who have become refractory to morphine or who suffer from respiratory side effects through its use".
- 28 June 2004: Elan files amendment to New Drug Application(NDA) to the U.S. Food and Drug Administration (FDA) for approval of Prialt(TM) (ziconotide) for the treatment of severe chronic pain based on additional efficacy and safety data.. The company anticipates a review time of approximately six months. Prialt Fact Sheet.
- 18 November 2004: PRIALT -Ziconotide- Receives Positive CHMP Recommendation For Intrathecal Treatment Of Severe Chronic Pain Elan Corporation, plc announced that PRIALT(TM) (ziconotide) has received a positive recommendation from the European Committee for Medicinal Products for Human Use (CHMP), the human medicines scientific body of the European Medicines Agency. The CHMP has recommended that Prialt be indicated for the treatment of severe, chronic pain in patients who require intrathecal (IT) analgesia. The CHMP's positive recommendation will now be proposed for final marketing approval by the European Commission. Final approval customarily follows the CHMP's recommendation in approximately three months. (see story from BioSpace.Com)
- 28 December, 2004 Elan Receives FDA Approval for PRIALT (Ziconotide Intrathecal Infusion) for Severe Chronic Pain -- Elan Corporation, plc (NYSE:ELN): Elan Corporation, plc announced that the U.S. Food and Drug Administration (FDA) has approved PRIALT(R) (ziconotide intrathecal infusion) for the management of severe chronic pain in patients for whom intrathecal (IT) therapy is warranted, and who are intolerant of or refractory to other treatment, such as systemic analgesics, adjunctive therapies or IT morphine. FDA approval of PRIALT was based on the treatment of more than 1,200 patients and three Phase III clinical trials, which evaluated the efficacy and safety of IT PRIALT in patients with severe chronic pain that was not adequately managed despite a regimen of systemic and/or IT analgesic and other drugs. The FDA approved the use of the non-opioid PRIALT(R) delivered by Medtronic's Synchromed(R) EL and Synchromed II infusion systems to treat chronic pain; this is the first new compound approved for use with a Medtronic infusion system in more than a decade.
- Feb. 22, 2005 -- DUBLIN, Ireland--(BUSINESS WIRE)-- Elan Receives Approval from the European Commission to Market PRIALT -100 Micrograms/ML Solution for Infusion- for Severe Chronic Pain. This approval follows a positive opinion in November 2004 by the European Committee for Medicinal Products for Human Use (CHMP), the human medicines scientific body of the European Medicines Agency.
- Marketing approval of PRIALT was based on the treatment of more than 1,000 patients, including three pivotal clinical studies, which evaluated the efficacy and safety of IT PRIALT in patients with severe chronic pain that was not adequately managed despite a regimen of systemic and/or IT analgesics.
- PRIALT, developed by scientists at Élan Corporation, has been approved for the management of severe chronic pain in patients for whom intrathecal (IT) therapy is warranted, and who are intolerant of or resistant to other treatment such as systemic analgesics, adjunctive therapies, or IT morphine. Prialt is approved for use only in the Medtronic SynchroMed®, SynchroMed® II Infusion System and Simms Deltec Cadd Micro® External Microinfusion Device and Catheter.
- PRIALT is the first new IT analgesic approved in more than two decades.
- The safety of Prialt was established in more than 1,200 patients, including those with pain related to failed back surgery, cancer, AIDS, and non-malignant causes.
- The majority of adverse events were mild or moderate. The four most frequently reported adverse events were dizziness, nausea, confusion, and headache.
- The longest treatment duration to date is more than seven years.
- PRIALT has been awarded orphan drug status in the European Union, which designates it as a product used for the diagnosis, prevention or treatment of life-threatening or very serious rare disorders or conditions.
- PRIALT has been evaluated as an IT infusion in more that 1,000 patients participating in chronic pain studies. The longest treatment duration to date has been more than six years. Severe chronic pain is defined as pain lasting longer than six months and has multiple causes, such as failed back surgery, injury, accident, cancer, AIDS, and other nervous system disorders.
- PRIALT led to pain relief in as early as the first week of treatment in some patients.
- PRIALT has been made available (since April 2005) to physicians and patients in the US.
- If you want to learn more about how PRIALT may help you, we encourage you to contact Élan directly. Information about Prialt, including prescribing information and comprehensive support services, is available through 1-888-PRIALT-1 (Toll Free in the USA) and at www.Prialt.com.
- Click on this link for the latest news on PRIALT. For updated information on PAIN and treatments go to to the National Pain Foundation (USA) web site.
- Essential patient information from the FDA about Ziconotide (marketed as Prialt).
(Prialt FDA Approved 2004, Patient Information Sheet Revised June 2004)
- What is Prialt ?
- Who Should Not Receive Prialt ?
- What are The Risks ?
- What Should I Tell My Health Care Professional ?
- Are There Any Interactions With Medicines or Foods ?
- How Am I Given Prialt ?
- July 28, 2005. Elan Reports Second Quarter 2005 Financial Results: "Prialt, a new treatment for severe chronic pain, was approved in the U.S. in December 2004 and launched in the U.S. in the first quarter of 2005. Revenue from Prialt for the second quarter of 2005 was $1.8 million, compared to $1.0 million in the first quarter of 2005."
- August 31 2005 Summary of information about Prialt
- Caution urged when prescribing Prialt A newly published review reveals that the drug has significant limitations - including potentially severe adverse effects in humans. The review appears in the September/October 2005 issue of American Journal of Hospice & Palliative Medicine.
Eric E. Prommer, MD (2005) Ziconotide: Can we use it in palliative care? American Journal of Hospice and Palliative Medicine, 22 (5) Sep/Oct 2005
SPC from the eMC on Prialt
The electronic Medicines Compendium (eMC) provides electronic Summaries of Product Characteristics (SPCs) and Patient Information Leaflets (PILs).
It provides information on thousands of licensed medicines available in the UK.
The eMC is continuously updated with new and revised SPC and PIL information which, after approval by the licensing authorities, is submitted directly by pharmaceutical companies.
On Feb 22, 2005, Elan received approval from the European Commission to market Prialt (100 microgram/ml solution for infusion) for treatment of severe chronic pain.
A patient information leaflet (PIL) is provided by Eisai is available. An SPC containing further information on 'Prialt solution for infusion' is available to view or as a print-friendly version.
Ziconotide (Prialt™) was approved in the EU for the treatment of severe, chronic pain in patients who require intrathecal analgesia.
Marketing approval was based on data from three pivotal studies in over 1000 patients, with severe chronic pain that was not adequately managed despite a regimen of systemic and/or intrathecal analgesics. Each of these studies reported significant improvement on the Visual Analogue Scale of Pain Intensity (VASPI). The longest treatment duration to date is over six years. The four most commonly reported adverse drug reactions were dizziness, nausea, nystagmus and confusion.
Prialt is in a class of non-opioid analgesics known as N-type calcium channel blockers. It is the synthetic equivalent of a naturally occurring conopeptide found in a marine snail known as Conus magus. It works by blocking N-type calcium channels on nerves that transmit pain signals.
On 10 September 2007, the Scottish Medicines Consortium (SMC) rejected the use of Ziconotide (Prialt®) within NHS Scotland, for the treatment of severe, chronic pain in patients who require intrathecal analgesia. Though it was acknowledged that compared to placebo, the drug improved pain scores in patients with chronic severe intractable pain despite treatment with systemic and/or intrathecal analgesia, the SMC said that the manufacturer did not present a sufficiently robust economic analysis. Read the SMC report here.
- Cognetix Inc.
; (BTC Special Report on Xenome pp. 12-13)
- Cognetix Announces Issuance of U.S. Patent on Contulakin-G to Treat Pain: The Company's lead pain therapeutic is contulakin-G (CGX-1160), a 16 amino acid conopeptide. CGX-1160 is a glycopeptide with a novel, non-opioid mechanism of action that offers a new and significantly advantageous approach to managing chronic intractable pain. CGX-1160 is highly water soluble and does not efficiently penetrate the blood brain barrier. CGX-1160 is efficacious in a wide range of preclinical pain models (acute, post-surgical, inflammatory, and neuropathic), and is particularly efficacious in models of chronic pain. CGX-1160 is easy to manufacture, stable, and has a wide therapeutic index. CGX-1160 appears to interact with the neurotensin receptor, and has demonstrated efficacy across a wide range of pre-clinical models of pain, including acute and chronic pain, inflammatory pain and neuropathic pain. CGX-1160 initially will be developed for the management of neuropathic pain, and has completed initial Phase I safety testing in man. In June 2004 the Company completed its Phase 1b study delivering CGX-1160 intrathecally in patients with chronic intractable pain caused by spinal cord injury. In this clinical trial, CGX-1160 demonstrated analgesic activity with no serious adverse events. The Company plans to initiate Phase 2 clinical trials in 2005, and a definitive long-term infusion, double-blind, placebo-controlled, dose-response study in 2006. In March 2005, CGX-1160 entered clinical trials for pain in terminally ill cancer patients. (Three other compounds have been outlicensed: CGX-1051 for Cardiac Reperfusion; CGX-1204 for neuromuscular block, and CGX-1007 for neuroprotection). Future work is directed at the design of CGX-1160 peptide analogs suitable for alternative routes of administration (not intrathecal); and 2) the design of orally available peptidomimetic and small molecule CGX-1160 scaffolds.
See Table for Molecular Target and Potential Indications for Conopeptides in a number of clinical conditions. See also pie chart graphic of Chronic pain market, USA. Check the developmental status of a number of their conopeptides.
Xenome Ltd. - (From the Archives)
- Xenome starts pre-clinical testing of cone shell analgesic Xenome's lead drug candidate is the chi-conotoxin, Xen2174, and is targeted to chronic cancer pain (neuropathic pain). The company has reported that Xen2174 is effective in suppressing pain in an animal model of neuropathic pain. In April 2004 Xenome announced that they had filed an Investigational New Drug (IND) application with the FDA's Center for Drug Evaluation and Research (CDER). The IND filing is a major milestone for Xenome as it represents the culmination of a rigorous and successful drug development program aimed at providing proof of efficacy and safety in animals to support a human clinical investigation of Xen2174. As reported recently, in animal models of pain, Xen2174 has been shown to provide superior pain relief when compared to morphine. Pending a successful IND application and Ethics approval Xenome will conduct the first Phase I clinical trial on Xen2174 in Australia with plans to conduct further clinical studies in Australia and in the US. The Phase I clinical trial will examine the safety and tolerability of Xen2174 administered to healthy volunteers. Successful completion of this trial will then provide the platform to conduct further safety and efficacy studies in cancer patients suffering from severe pain. In a Media Release, 20 July 2004, Xenome announced commencement of a Phase I clinical trial on Xen2174. This Phase I trial is a randomised, placebo-controlled, double blind, dose-escalating study involving up to 20 healthy male volunteers. The primary purpose of this trial is to evaluate the safety and tolerability of Xen2174 following intravenous administration. "Additional information on the pharmacokinetics and potential anti-nociceptive effects of Xen2174 will also be examined during the trial", commented Xenome's Head of Drug Development, Dr Michael Thurn. On Friday 13 August, 2004, Xenome announced a realignment of its R&D focus on major pharmaceutical markets in the United States, and a plan to secure further financing. As part of this realignment, it was announced that Xenome's CEO, Dr Tony Evans, will step down to allow the appointment of a CEO, likely to be based in the United States. Xenome has appointed an internationally experienced Clinical Development Manager to manage Xenome's lead drug, Xen2174, currently in Phase I clinical trials. A CMC Manager has also been assigned to oversee drug product production. Another planned appointment, also likely to be located in the US, is a Vice President of Business Development. Co-founder, former General Manager and current Head of Research at Xenome, Dr Roger Drinkwater, will be acting CEO during this transition period and will establish the framework for the next phase of Xenome's development.
November 15, 2005, BRISBANE, Australia and SAN DIEGO, Nov. 15 /PRNewswire/ -- Xenome Limited today announced it had commenced a Phase I/IIa trial of Xen2174, a new class of peptide therapeutic for the treatment of severe intractable pain. (see Story from BioSpace.com)
AMRAD Corporation Limited
AMRAD Fast Tracks Development of Chronic Pain Drug.
Severe Pain - AM336: AM336 is a pain reliever for chronic pain. Uncontrolled chronic pain is a frequent complication of a multitude of diseases, including cancer, nerve damage and traumatic accidents. Opiates such as morphine continue to be the mainstay of severe pain management despite problems of variable efficacy, significant side effects and the development of tolerance. AM336 is an intrathecally delivered compound that acts by a completely different mechanism to opiates and blocks pain signals in the spinal cord.
A Phase I/II safety study of AM336 in cancer patients suffering from chronic severe pain was successfully completed in February 2002. The study showed AM336 to be safe and have potential to reduce pain in patients with severe pain that was not effectively treated by existing analgesics. AM336 has been nominated for out-licensing and suitable licensing partners for AM336 are being actively pursued.
- More from the Archives
- AMRAD Focuses Product Portfolio - (and pulls out of AM336 development!)In 2004, AMRAD restructured and became Zenyth Therapeutics Limited (Zenyth). Zenyth resolved to focus its activities on the development and commercialisation of antibody-based therapies in the areas of inflammation and cancer. In June 2005, Zenyth completed a transaction with Biocomm Services and Monash University establishing a new company, CNSBio Pty Ltd, with expertise in the research and discovery of novel therapies for pain. Zenyth’s portfolio of neurological compounds, which now fall outside its strategic focus, is the subject of an option licensing agreement with CNSBio Pty Ltd. Zenyth is no longer actively pursuing the development of drugs for neurological diseases.
Metabolic Pharmaceuticals Limited
- Metabolic obtains licence to novel analgesic: Metabolic are proceding with pre-clinical toxicity testing of ACV1, a novel and promising analgesic alpha-conotoxin from an Australian cone shell, Conus victoriae, preliminary to planned Stage I Clinical Trials for diabetic neuropathy early in 2005. (See ASX Announcement, March 9, 2004; and ASX Announcement, September 22, 2004. Click to access Nature News article (June 2004) on conotoxins as drug candidates "One slip and you're dead...". See also, media release from University of Melbourne 19 August 2004 "Snail toxins provide pain relief". As reported in their investor update 8 March 2005, data from the preclinical efficacy and toxicology studies is now in hand to support human dosing of ACV1 in Phase 1 and Phase 2a human clinical trials. The package is currently (Q2/05) being compiled for submission for approval to the Royal Adelaide Hospital ethics committee to commence a Phase 1 human clinical trial in healthy volunteers. See also Aegis Equities Report of 8 March 2005.
On 14 June 2005, Metabolic announced receipt of a AUD$449,902 “Commercial Ready” AusIndustry Grant to support the Phase 1 Clinical Trial for ACV1. The ACV1 Phase 1 trial is expected to commence once ethics approval is obtained and is projected to finish before the end of the year. The aim of the trial is to evaluate the safety and tolerability of single and multiple doses (once daily for one week) of ACV1 in healthy normal males. A successful result would enable the conduct of Phase 2 studies in patients during 2006.
On 25 June 2005, Graeme O'Neil wrote about our Cone shell (Conus victoriae) work in an article in The Age (Melbourne) entitled "Pain-killer comes out of its shell".
In summary: "ACV1 is the first in a potential new class of drugs to specifically treat neuropathic (nerve) pain. Current therapies rely largely on the ‘off-label’ use of anticonvulsants, antidepressants and local anaesthetics, which have unimpressive efficacy and doselimiting side-effects. The potential range of indications for ACV1 extend to
neuropathic pain in diabetics, post-herpetic neuralgia (“shingles”), sciatica and many
other neuropathic pain conditions currently underserved by pharmaceutical treatment
ACV1 specifically blocks a subtype of a class of receptors in the peripheral nervous
system called neuronal nicotinic acetylcholine receptors (nAChR). ACV1 can be
administered by once daily subcutaneous injections providing substantial relief in
several animal models of neuropathic pain without apparent adverse effect. Phase 1
clinical trials are planned for Q2 2005".
Source: Metabolic Investor Update 20 April 2005.
- 23 June 2005. ASX announcement from Metabolic Pharmaceuticals that ACV1 Phase 1 Clinical Trial Commences
- 23rd June 2005Download ASX Announcement as pdf. ACV1 Phase 1 Clinical Trial Commences.
Abstract: Metabolic announced that dosing in the ACV1 Phase 1 human clinical trial commenced on schedule today in Adelaide, South Australia. Metabolic’s innovative pain drug is being developed in response to a serious need for new pain killers with novel modes of action. The drug (ACV1) has thus far demonstrated in animal studies that it reduces neuropathic (nerve) pain, appears to accelerate the functional recovery of damaged nerves, and is well tolerated. The Phase 1 study is the first time ACV1 has been administered to humans. This is a randomised, double-blind, placebo-controlled Phase 1 study. The main aims are to assess the safety, tolerability, and pharmacokinetics of both single doses and multiple (7) daily doses of ACV1 administered by subcutaneous injection in healthy, male volunteers. Up to six dose levels from 5 micrograms per kg to 400 micrograms per kg will be evaluated in both the single ascending dose and multiple ascending dose parts of the study. At each dose level five different subjects will be studied; four subjects will be randomised to receive the active ACV1 drug and one subject will be randomised to receive placebo (a solution without the active drug) for comparison. The multiple ascending dose administrations will follow the initial single ascending dose part of the study. Volunteers will be monitored for a range of safety parameters while resident in the clinical study unit. In addition, blood samples will be collected for the measurement of ACV1 levels to ascertain the pharmacokinetics of the drug i.e. information on the way the drug is absorbed, distributed and eliminated from the body. The trial is expected to be finished by the end of 2005. A positive outcome would allow Phase 2 safety and efficacy trials in patients suffering from neuropathic pain to be conducted in 2006.
See these links for further details.
27 June 2005: University of Melbourne: UniNews article Human Trials for Pain Relief Drugs from the Sea
28th October 2005 CEO Presentation at AGM October 2005 by Roland Scollay PhD, CEO
23 November, 2006
ACV1 PreClinical Update
Metabolic's neuropathic pain drug ACV1 - additional preclinical studies reveal greater potential This ASX Announcement by Metabolic Pharmaceuticals reports that the:
- Latest oral version of ACV1 works as well as the injected version in new animal studies
- Provides proof-of-concept for Metabolic's Oral Peptide Delivery Platform
- An independent study provides new knowledge about how ACV1 works and reveal the likely biochemical target for ACV1
29 November, 2006
ACV1 Clinical Trials Update
Metabolic's neuropathic pain drug, ACV1 - additional clinical studies reveal:
- First patients have been treated with ACV1 in the Phase 2A sciatica trial
- A separate trial to test safety of a higher dose level in healthy volunteers has commenced – important information for regulatory authorities and potential licensing partners
- The three clinical trials for ACV1 in progress or final planning are progressing on time
30 November, 2006
Clinical trials with ACV1 to treat sciatica
Sciatic pain trial: The Great Barrier Reef could hold the key to curing sciatic pain. Australian scientists have developed a drug, called ACV1, using an extract from a venomous sea snail (Conus victoriae). Researchers are looking for participants who have suffered sciatic pain for more than three months. To take part in this Phase II Clinical Trial call Adelaide University: +61-8-8222 5422.
Clinical trials with ACV1 are being conducted at the Royal Adelaide Hospital, South Australia, by CMAX - Clinical Studies Unit (A Division of IDT Australia Ltd), under the direction of Prof. Guy Ludbrook, Professor and Head of Anaesthesia and Intensive Care, University of Adelaide.
Clicking on the following link activates a video segment from the Channel 7 News in which Prof. Ludbrook describes the
Clinical Trials to treat sciatica with ACV1 at Royal Adelaide Hospital.
7 December, 2006
Acceleration of development of the oral version of ACV1 for neuropathic pain
Dr. Roland Scollay, CEO of Metabolic Pharmaceuticals, said "proceeds from the (A$10.5 million) share placement will be used to accelerate the development of the recently announced oral version of the Company's neuropathic pain drug, ACV1 (synthetic conotoxin Vc1.1), and to actively progress its Oral Peptide Delivery Platform - the technology platform used to convert ACV1 from an injectable to an oral drug.The proceeds will be used, in part, to determine to what extent this technology can be applied to other currently injected peptide drugs on the market or in develoment."
For further details view or download the ASX announcement of 7 December.
14 August 2007
Metabolic Pharmaceuticals discontinues clinical trial program for neuropathic pain drug, ACV1 (conotoxin Vc1.1)
ASX Announcement. Melbourne 14 August 2007: Metabolic Pharmaceuticals reported having received new data regarding the ability of alpha-conotoxin Vc1.1 (ACV1) to block the human alpha9alpha10 nicotinic acetylcholine receptor, the probable target of ACV1.
Extract:"Despite the Phase 2A trial of ACV1 in sciatic neuropathic pain having been recently completed, the results of that trial (which are yet to be fully analysed) have been overshadowed by the results of contemporaneous in vitro studies on the ability of ACV1 to block the human alpha9alpha10 nicotinic acetylcholine receptor (nAChR), the probable target of ACV1.
This second study, which was commenced shortly after the alpha9alpha10 nAChR was identified as the probable molecular target for ACV1 in rats, was undertaken to accurately inform dose selection in future clinical trials.
While there is normally similar activity of drug candidates across human and rodent receptors, the study results showed that ACV1 is dramatically less able to block the human alpha9alpha10 nAChR than it is to block the equivalent rat receptors."
What this means for the ACV1 pain programme: "This lower ability of ACV1 to block the human alpha9alpha10 nAChR means that much larger doses of ACV1 than the dose used in the recently completed Phase 2A trial would be necessary to see effects in humans. Doses at the required level are unlikely to be feasible (impractical to inject and cost of goods prohibitive). The Company has therefore concluded that the ACV1 clinical programme is no longer tenable. As a consequence of that decision, the ongoing Phase 2A trial of ACV1 in diabetic neuropathic pain and post-herpetic neuralgia (shingles related pain) will also be stopped. No further ACV1 trials are foreseen."
"The Company will focus its research and development on the Oral Peptide Delivery Platform, and will continue to search for new drugs to in-license or acquire."
Article from Medtronic on Chronic Pain "Tame the Pain" - includes video of Medtronic Synchromed Pump
Clinical Trial Search Form for Chronic Pain (Veritas Medicine) USA and Canada only.
Slide show on Aggressive Pharmacological Treatment of Pain by Marco Pappagallo, MD, Director, HJD Pain Treatment Center, Mt Sinai / NYU Health, New York, NY
Article from Elan on Chronic Pain
How a New Drug gets from the Research Laboratory to your Medicine Cabinet.
Visit the Cone shell Bookshop
4 Cone Shell Posters: (1) Poster of 50 different Cone Shells "Coquillages des Mers du Sud / Shells from the South Seas"; (2)
Dominican Cone; (3) Cone, Murex and Mitre; and (4) Volutes, Cone and Cowries
Information about CONCH-L mailserv
Starting point for beginning collectors
Hawai'i Coral Reef Network. Lots of Cone shells live and shells.
Links to other mollusc sites
Questacon: Background Notes. Vicious Venoms - Cone Shell
ITIS = Integrated Taxonomic Information System
Bryan Grieg Fry's article about conotoxins - on his web site VENOMDOC
Bruce Livett's research page at Bio21 Research Institute, Melbourne, Australia.
Read Bruce Livett's article "Beauty and the Beast: Molecular Prospecting for Novel Drugs from the Sea". Address to The Royal Society of Victoria, Thursday 13 March 1997.
View Bruce Livett's recent research publications.
Conus textile on the prowl
Rik J Deitsch of Florida Atlantic University maintains the U.S.S. Conotoxin Homepage. This site provides a comprehensive list of Atlantic Cones by Dr. Edward Petuch as well as a list and directory of where certain Cone species can be found in Florida waters and the best way to collect them. In the future, a complete database of their sequences, including bioassay work with each sequence performed at Cognetix will be added.
Dr. Bruce Livett's Research (at the Department of Biochemistry and Molecular Biology, Univ. of Melbourne, Australia)
Kevin S. Cummings' "Rogue's Gallery" of past scientists in the fields of conchology and malacology giving basic biographic / bibliographic information on each.
Contact List of folk interested in conotoxins
(why not submit your name ?)
To all interested in molluscan conservation: Tentacle is the Newsletter of the Mollusc Specialist Group of the Species Survival Commission of the IUCN (International Union for the Conservation of Nature and Natural Resources -- or the World Conservation Union). The focus is mollusk conservation. However, many issues are linked to the threats faced by mollusks and the Editor (Dr. Robert H. Cowie) encourages submisions by email of anything relevant to mollusc conservation, and also citations to recent publications dealing with mollusk conservation, notices of meetings dealing with mollusks, websites dealing with mollusks, etc. (31 December is the deadline for submissions).
Conference : Final Program and Posters on cone shells and conotoxins delivered at the Inaugural Meeting "From Venoms to Drugs" on Heron Island, Queensland, Australia (August 16-21, 1998). The abstracts of these talks from the Conference Proceedings will be published in Toxicon.
Links to Heron Island Research Station (HIRS),
and One Tree Island Research Station, sites for BGL's Field Trip, August 1998
Links to Lizard Island Research Station (LIRS),
, site for BGL's Field Trip, March 1999
Links from other sites to this Cone Shell and Conotoxins HomePage