FAKTENTHREAD: Studien zu XOMA052 (Gevokizumab) u.a. IL-1-Blockern - 500 Beiträge pro Seite

[extremrelaxer]

Hallo zusammen,

aufgrund der wohl im März anstehenden Flut an Nachrichten zu XOMA 052 (Gevokizumab) eröffne ich hier zur Verbesserung der Übersichtlichkeit einen Faktenthread.

Jeder, der hier Studien zu Gevokizumab und anderen konkurierenden Interleukin-1-Blockern reinstellt ist herzlich dazu eingeladen!

Zur Verbesserung der Übersichtlichkeit wäre es toll, wenn hierbei folgendes enthalten wäre:

1. Datum der Studie
2. Überschrift der Studie
3. Abstract oder Kernaussage der Studie
4. Ein Quellenlink

und ebenfalls von Interesse:

5. eigener Komentar

Die Diskussion sollte sich wenn notwendig ausschließlich auf die Studiendaten beschränken. Kommentare anderer Art, z.B. zum Kursverlauf und ähnlichem bitte weiterhin im Hauptthread!

Auf eine interessante Diskussion!

LG, ER

[beachboy22]

HI ER...

bist du schon wieder voll investiert? Überlege mir eine Posi so bei 4.8-4.9 USD aufzubauen...mal schauen ob es klappt...

[extremrelaxer]

Antwort auf Beitrag Nr.: 41.092.622 von beachboy22 am 23.02.11 15:41:51

Hi beachy,
das ist der falsche Ort für Smalltalk!
LG, ER



Am 17.02.11 hat XOMA ein Patent zu einem Verfahren beantragt, welches dazu dient, die Affinität der AK-Bindung zu steigern.


Abstract:

"The present disclosure relates to methods and materials for enhancing the binding affinity of an antibody by means of generating a library or an array of targeted amino acid changes (e.g., mutations) at one or more positions in an antibody variable domain. The present disclosure relates to libraries or arrays and their uses for enhancing antibody affinity. The present disclosure relates to methods and materials for mutagenesis, including for the generation of novel or improved antibody variable domains and libraries or arrays of mutant antibody variable domains or nucleic acids encoding such mutant or modified variable domains".

Trockener Stoff:

http://www.faqs.org/patents/app/20110039722

[extremrelaxer]

Links zu aktuellen Studien zu IL-1 / IL-1-Blockern (nur 2011). Aus Zeitgründen kann ich aktuell nicht inhaltlich darauf eingehen. Aufzählung unvollständig. Suchbegriffe: XOMA, Anakinra, Il-1

Trends Mol Med. 2011 Feb;17(2):57-64. Epub 2010 Dec 14.
Inflammasomes and autoimmunity.
Shaw PJ, McDermott MF, Kanneganti TD.
http://www.ncbi.nlm.nih.gov/pubmed/21163704

Trends Mol Med. 2011 Feb;17(2):57-64. Epub 2010 Dec 14.

Inflammasomes and autoimmunity.
Shaw PJ, McDermott MF, Kanneganti TD.
http://www.ncbi.nlm.nih.gov/pubmed/21163704

J Leukoc Biol. 2011 Feb 17. [Epub ahead of print]
Autoinflammation: translating mechanism to therapy.
Doherty TA, Brydges SD, Hoffman HM.
http://www.ncbi.nlm.nih.gov/pubmed/21330349

Nat Rev Drug Discov. 2011 Mar;10(3):166.

Deal watch: XOMA and Servier to develop anti-IL-1β antibody for inflammatory diseases.
[No authors listed]
http://www.ncbi.nlm.nih.gov/pubmed/21358727
Kommentar: Leider kein Abstract erhältlich!

MAbs. 2011 Jan-Feb;3(1):49-60. Epub 2011 Jan 1.

XOMA 052, a potent, high-affinity monoclonal antibody for the treatment of IL-1β-mediated diseases.
Owyang AM, Issafras H, Corbin J, Ahluwalia K, Larsen P, Pongo E, Handa M, Horwitz AH, Roell MK, Haak-Frendscho M, Masat L.
XOMA (US) LLC; Preclinical Department; Berkeley, CA USA.
http://www.ncbi.nlm.nih.gov/pubmed/21048425

Curr Opin Mol Ther. 2010 Dec;12(6):755-69.

Gevokizumab, an anti-IL-1β mAb for the potential treatment of type 1 and 2 diabetes, rheumatoid arthritis and cardiovascular disease.
Geiler J, McDermott MF.
http://www.ncbi.nlm.nih.gov/pubmed/21048425


http://www.ncbi.nlm.nih.gov/pubmed/21048425


Vnitr Lek. 2011 Jan;57(1):97-112.
[Schnitzler syndrome: case report, the experience with glucocorticoid and anakinra (Kineret) therapies and monitoring of systemic cytokine response].
http://www.ncbi.nlm.nih.gov/pubmed/21351669

Curr Opin Rheumatol. 2011 Feb 22. [Epub ahead of print]
Treatment with biologics of pregnant patients with rheumatic diseases.
Ostensen M, Förger F.
http://www.ncbi.nlm.nih.gov/pubmed/21346578

Cochrane Database Syst Rev. 2011 Feb 16;2:CD008794.
Adverse effects of biologics: a network meta-analysis and Cochrane overview.
Singh JA, Wells GA, Christensen R, Tanjong Ghogomu E, Maxwell L, Macdonald JK, Filippini G, Skoetz N, Francis D, Lopes LC, Guyatt GH, Schmitt J, La Mantia L, Weberschock T, Roos JF, Siebert H, Hershan S, Lunn MP, Tugwell P, Buchbinder R.
http://www.ncbi.nlm.nih.gov/pubmed/21328309

Regul Toxicol Pharmacol. 2011 Feb 12. [Epub ahead of print]
Integration of efficacy, pharmacokinetic and safety assessment of interleukin-1 receptor antagonist in a preclinical model of arthritis.
Zuurmond AM, Koudijs A, van El B, Doornbos RP, van Manen-Vernooij BC, Bastiaans JH, Penninks AH, van Bilsen JH, Cnubben NH, Degroot J.
http://www.ncbi.nlm.nih.gov/pubmed/21300126

Arthritis Rheum. 2011 Feb;63(2):545-55. doi: 10.1002/art.30128.
Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series.
Nigrovic PA, Mannion M, Prince FH, Zeft A, Rabinovich CE, van Rossum MA, Cortis E, Pardeo M, Miettunen PM, Janow G, Birmingham J, Eggebeen A, Janssen E, Shulman AI, Son MB, Hong S, Jones K, Ilowite NT, Cron RQ, Higgins GC.
http://www.ncbi.nlm.nih.gov/pubmed/21280009

Semin Arthritis Rheum. 2011 Jan 28. [Epub ahead of print]
Interleukin-1 Targeting Drugs in Familial Mediterranean Fever: A Case Series and a Review of the Literature.
Meinzer U, Quartier P, Alexandra JF, Hentgen V, Retornaz F, Koné-Paut I.
http://www.ncbi.nlm.nih.gov/pubmed/21277619

Dtsch Med Wochenschr. 2011 Feb;136(5):172-5. Epub 2011 Jan 26.
[Recent advances in the treatment of type 1 diabetes mellitus].
[Article in German]
Schloot NC, Roden M, Bornstein SR, Brendel MD.
http://www.ncbi.nlm.nih.gov/pubmed/21271474

Z Rheumatol. 2011 Feb;70(2):114-122.
[Combination therapy using methotrexate with DMARDs or biologics - current status.]
[Article in German]
Krüger K.
http://www.ncbi.nlm.nih.gov/pubmed/21267733

Rheumatol Int. 2011 Jan 15. [Epub ahead of print]
Treatment of refractory adult-onset still's disease with tocilizumab: report of two cases and review of the literature.
Thonhofer R, Hiller M, Just H, Trummer M, Siegel C, Dejaco C.
http://www.ncbi.nlm.nih.gov/pubmed/21240503

Rheumatol Int. 2011 Jan 15. [Epub ahead of print]
Long-term response after 6-year treatment with anakinra and onset of focal bone erosion in neonatal-onset multisystem inflammatory disease (NOMID/CINCA).
Rigante D, Leone A, Marrocco R, Laino ME, Stabile A.
http://www.ncbi.nlm.nih.gov/pubmed/21240490

J Rheumatol. 2011 Jan 20. [Epub ahead of print]
Comparison of Certolizumab Pegol with Other Anticytokine Agents for Treatment of Rheumatoid Arthritis: A Multiple-treatment Bayesian Metaanalysis.
Launois R, Avouac B, Berenbaum F, Blin O, Bru I, Fautrel B, Joubert JM, Sibilia J, Combe B.
http://www.ncbi.nlm.nih.gov/pubmed/21239748

Clin Rheumatol. 2011 Jan 11. [Epub ahead of print]
Secondary failure to treatment with recombinant human IL-1 receptor antagonist in Chinese patients with rheumatoid arthritis.
Bao J, Yue T, Liu W, Zhang Q, Zhou L, Xu HJ, Dai SM.
http://www.ncbi.nlm.nih.gov/pubmed/21221689

Autophagy. 2011 Mar 1;7(3). [Epub ahead of print]
Phagocytosis of cells dying through autophagy induces inflammasome activation and IL-1β release in human macrophages.
Petrovski G, Ayna G, Májai G, Hodrea J, Benkő S, Mádi A, Fésüs L.
http://www.ncbi.nlm.nih.gov/pubmed/21217200

J Rheumatol. 2011 Jan;38(1):180-1.
Combination therapy of abatacept and anakinra in children with refractory systemic juvenile idiopathic arthritis: a retrospective case series.
Record JL, Beukelman T, Cron RQ.
http://www.ncbi.nlm.nih.gov/pubmed/21196588

Pharmacotherapy. 2011 Jan;31(1):39-51.
Effectiveness of biologic therapies for rheumatoid arthritis: an indirect comparisons approach.
Devine EB, Alfonso-Cristancho R, Sullivan SD.
http://www.ncbi.nlm.nih.gov/pubmed/21182357

J Clin Rheumatol. 2011 Jan;17(1):23-7.
Rapid and sustained remission of systemic juvenile idiopathic arthritis-associated macrophage activation syndrome through treatment with anakinra and corticosteroids.
Bruck N, Suttorp M, Kabus M, Heubner G, Gahr M, Pessler F.
http://www.ncbi.nlm.nih.gov/pubmed/21169853

J Rheumatol. 2011 Mar;38(3):516-8. Epub 2010 Dec 15.
Anti-interleukin 1 treatment for patients with familial mediterranean Fever resistant to colchicine.
Ozen S, Bilginer Y, Aktay Ayaz N, Calguneri M.
http://www.ncbi.nlm.nih.gov/pubmed/21159830

[extremrelaxer]

OT: Eine Studie von Relevanz (vom 03.03.11) zu einem Diabetes mellitus-Konkurrenzpräparat aus der Gruppe der GLP-1-Rezeptorantagonisten (Amylin Pharmaceuticals, Eli Lilly und Alkermes).
Aktien am abstürzen! Kein Wunder! Vergleicht mal das Nebenwirkungsprofil von XOMA052 (Studie 2a-Ergebnisse) mit den unten angeführten Wahrscheinlichkeiten von unerwünschten NW der GLP-1-Rezeptorantagonisten


DURATION-6 Top-Line Study Results Announced
SAN DIEGO, INDIANAPOLIS and WALTHAM, Mass., March 3, 2011 /PRNewswire via COMTEX/ --

Amylin Pharmaceuticals, Inc. (Nasdaq: AMLN), Eli Lilly and Company (NYSE: LLY) and Alkermes, Inc. (Nasdaq: ALKS) today announced top-line results from DURATION-6, a head-to-head study designed to compare weekly BYDUREON(TM) (exenatide extended-release for injectable suspension), an investigational type 2 diabetes therapy, to daily Victoza(R) (liraglutide (rDNA origin) injection). Both drugs are members of the class of type 2 diabetes medications known as glucagon-like peptide-1 (GLP-1) receptor agonists.


This open-label 26-week, multicenter clinical study compared BYDUREON (2 mg weekly) to Victoza administered at the maximum approved dose of 1.8 mg daily. The study was designed to measure A1C, an assessment of average blood sugar, and to evaluate safety and tolerability.

Results showed that patients receiving BYDUREON experienced a reduction in A1C of 1.3 percentage points from baseline, compared to a reduction of 1.5 percentage points for Victoza. BYDUREON did not meet the pre-specified primary endpoint of non-inferiority to Victoza.

More than 85 percent of patients in both treatment arms completed the study. Gastrointestinal adverse events occurred more frequently among Victoza patients (nausea reported among 20 percent of patients, vomiting 11 percent, diarrhea 13 percent) compared with BYDUREON patients (nausea 9 percent, vomiting 4 percent, diarrhea 6 percent). Injection site nodule occurred more frequently among BYDUREON users (10 percent) compared with Victoza users (1 percent). There were no major hypoglycemia events in either treatment group.

Further evaluation of this data set is underway and, when complete, the companies plan to submit the full study results for publication.

"While this study did not meet its primary endpoint, these results reinforce the important role of GLP-1 receptor agonists in the treatment of type 2 diabetes," said Gwen Krivi, M.D., vice president, product development, Lilly Diabetes. "This is the sixth DURATION study showing once-weekly BYDUREON had a significant A1C reduction from baseline. If approved, BYDUREON could provide millions of patients a once-weekly treatment option."

BYDUREON (pronounced by-DUR-ee-on) is the proposed brand name for exenatide once weekly. It is an investigational, extended-release medication for type 2 diabetes designed to deliver continuous therapeutic levels of exenatide in a single weekly dose. BYDUREON is a once-weekly formulation of exenatide, the active ingredient in BYETTA(R) (exenatide) injection, which has been available in the U.S. since June 2005 and is used in more than 70 countries worldwide to improve glycemic control in adults with type 2 diabetes.

The New Drug Application for BYDUREON was submitted to the U.S. Food and Drug Administration (FDA) in 2009. The FDA issued a complete response letter and requested further data in October 2010. The companies plan to submit a response in the second half of 2011.

Study Design

DURATION-6 is the sixth in a series of studies comparing BYDUREON to other type 2 diabetes medications. The 26-week, head-to-head, open-label, superiority study enrolled approximately 900 patients in 19 countries outside the U.S. with type 2 diabetes who were not achieving adequate A1C control with diet and exercise in conjunction with metformin, a sulfonylurea, metformin plus a sulfonylurea or metformin plus Actos(R) (pioglitazone HCI). Patients had an average type 2 diabetes diagnosis of more than eight years. The patients were randomized to receive subcutaneous injection of either BYDUREON (2 mg, once per week) (n=461) or Victoza (forced titration to 1.8 mg, once per day) (n=451). The primary endpoint was reduction in A1C, while secondary endpoints included change in body weight along with other parameters of glucose control, cardiovascular health and safety and tolerability.

About Diabetes

Diabetes affects nearly 26 million people in the U.S. and an estimated 285 million adults worldwide.(i, ii) Approximately 90-95 percent of those affected have type 2 diabetes. Diabetes costs approximately $174 billion per year in direct and indirect medical expenses.(iii)

According to the Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey, approximately 60 percent of people with diabetes do not achieve their target blood sugar levels with their current treatment regimen.(iv) In addition, 85 percent of type 2 diabetes patients are overweight and 55 percent are considered obese.(v) Data indicate that weight loss (even a modest amount) supports patients in their efforts to achieve and sustain glycemic control.(vi, vii)

About BYETTA(R) (exenatide) injection

BYETTA was the first GLP-1 receptor agonist to be approved by the FDA for the treatment of type 2 diabetes. BYETTA exhibits many of the same effects as the human incretin hormone GLP-1. GLP-1 improves blood sugar after food intake through multiple effects that work in concert on the stomach, liver, pancreas and brain.

BYETTA is an injectable prescription medicine that may improve blood sugar (glucose) control in adults with type 2 diabetes mellitus, when used with a diet and exercise program. BYETTA is not insulin and should not be taken instead of insulin. BYETTA is not currently recommended to be taken with insulin. BYETTA is not for people with type 1 diabetes or people with diabetic ketoacidosis. BYETTA has not been studied in people who have pancreatitis.

BYETTA provides sustained A1C control and low incidence of hypoglycemia when used alone or in combination with metformin or a thiazolidinedione, with potential weight loss (BYETTA is not a weight-loss product). BYETTA was approved in the U.S. in April 2005 and has been used by more than 1.5 million patients since its introduction. See important safety information below. Additional information about BYETTA is available at www.BYETTA.com.

Important Safety Information for BYETTA(R) (exenatide) injection

Based on post-marketing data, BYETTA has been associated with acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. The risk for getting low blood sugar is higher if BYETTA is taken with another medicine that can cause low blood sugar, such as a sulfonylurea. BYETTA should not be used in people who have severe kidney problems, and should be used with caution in people who have had a kidney transplant. Patients should talk with their healthcare provider if they have severe problems with their stomach, such as delayed emptying of the stomach (gastroparesis) or problems with digesting food. Severe allergic reactions can happen with BYETTA.

The most common side effects with BYETTA include nausea, vomiting, diarrhea, dizziness, headache, feeling jittery, and acid stomach. Nausea most commonly happens when first starting BYETTA, but may become less over time.

These are not all the side effects from use of BYETTA. A healthcare provider should be consulted about any side effect that is bothersome or does not go away.

For additional important safety information about BYETTA, please see the full Prescribing Information (www.BYETTA.com/pi) and Medication Guide (www.BYETTA.com/mg).

About Amylin, Lilly and Alkermes

Amylin, Lilly and Alkermes are working together to develop BYDUREON, a subcutaneous injection of exenatide for the treatment of type 2 diabetes based on Alkermes' proprietary Medisorb(R) technology for long-acting medications. BYDUREON is not currently approved by any regulatory agency.

Amylin Pharmaceuticals is a biopharmaceutical company dedicated to improving lives of patients through the discovery, development and commercialization of innovative medicines. Amylin's research and development activities leverage the Company's expertise in metabolism to develop potential therapies to treat diabetes and obesity. Amylin is headquartered in San Diego.

Through a long-standing commitment to diabetes care, Lilly provides patients with breakthrough treatments that enable them to live longer, healthier and fuller lives. Since 1923, Lilly has been the industry leader in pioneering therapies to help healthcare professionals improve the lives of people with diabetes, and research continues on innovative medicines to address the unmet needs of patients.

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Lilly provides answers - through medicines and information - for some of the world's most urgent medical needs.

Alkermes, Inc. is a fully integrated biotechnology company committed to developing innovative medicines to improve patients' lives. Alkermes' robust pipeline includes extended-release injectable, pulmonary and oral products for the treatment of prevalent, chronic diseases, such as central nervous system disorders, addiction and diabetes. Headquartered in Waltham, Mass., Alkermes has a research facility in Massachusetts and a commercial manufacturing facility in Ohio.



http://phx.corporate-ir.net/phoenix.zhtml?c=101911&p=irol-ne…

[ottl2000]

Hey ER

Hier noch ein Artikel. Weiss allerdings nicht ob der schon gepostet

wurde.

Gruss Ottl

[ottl2000]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038011/

[extremrelaxer]

Antwort auf Beitrag Nr.: 41.152.539 von ottl2000 am 05.03.11 13:22:47

Hi Ottl. Ja die Studie ist oben mit aufgeführt und war aber schon Mitte Dezember online recherchierbar. Ich hatte sie jedenfalls im Diskussionsboard bereits Mitte Dezember kommentiert und war Mitte Dezember aufgrund dieser Studie bei 2,40 USD all-in gegangen. Es ist meiner Meinung nach sicherlich eine der interessanteren Studien. Von großer Relevanz hielt ich die Studie damals insbesondere aufgrund dem Vergleich mit Anakinra. Den Biotech-Analysten war dies übrigens auch klar geworden (mehrere Tage, nachdem wir das hier diskutiert hatten). Die Übereinstimmende Aussage der Analysten lautete dann viele Tage später: XOMA-052 könnte den anderen IL-Blockern überlegen sein. Diese Analystenmeinungen waren dann widerum ursächlich für den Kursanstieg im Dezember 2010.
Ein schönes Beispiel dafür, wie lange Analysten pennen können und wie profitabel es sein kann, selbst zu recherchieren!


Einige Kernaussagen waren:
- Wirkung von XOMA052 bei künstlich durch Uratkristalle (Harnsäure) induzierter Peritonitis (Preklinische Studie zur Gicht)
- Vergleich mit Anakinra (XOMA 20-mal potenter!)
- Wirkungsweise bei IL-1-Rezeptor-Mutationen (leider ohne Angabe von Häufigkeiten der Mutationen)
- Ausirkung der IL-1-beta-Blockade auf IL-6- und IL-8-Spiegel
- Begründung des hohen Sicherheitsprofils und der Wirkungsstärke durch die hohe Affinität und Spezifität:
"To overcome these limitations, we sought to design and develop a “best-in-class” anti-IL-1β therapeutic antibody, XOMA 052. This high affinity antibody specifically inhibits IL-1β activity with a unique mechanism of action.18 Such specificity for IL-1β alone will have the added advantage of sparing both IL-1α, which could provide a safety margin for protection against potential infections and IL-1Ra, which is the natural antagonist of the IL-1 signaling pathway. Indeed, inactivation of IL-1Ra would work against the very purpose of the therapeutic drug."

Um diese Studie handelt es sich:

MAbs. 2011 Jan-Feb;3(1):49-60. Epub 2011 Jan 1.

XOMA 052, a potent, high-affinity monoclonal antibody for the treatment of IL-1β-mediated diseases.
Owyang AM, Issafras H, Corbin J, Ahluwalia K, Larsen P, Pongo E, Handa M, Horwitz AH, Roell MK, Haak-Frendscho M, Masat L.
XOMA (US) LLC; Preclinical Department; Berkeley, CA USA.
http://www.ncbi.nlm.nih.gov/pubmed/21048425


Grüsse, ER

[extremrelaxer]

Studie zu Rilonacept bei Gicht:

Rheumatology (Oxford). 2011 Mar 3. [Epub ahead of print]

Minimally important differences of the gout impact scale in a randomized controlled trial.
Khanna D, Sarkin AJ, Khanna PP, Shieh MM, Kavanaugh AF, Terkeltaub RA, Lee SJ, Singh JA, Hirsch JD.

Department of Medicine, Division of Rheumatology, David Geffen School of Medicine at UCLA, Los Angeles, Health Services Research, Division of Rheumatology, Allergy, and Immunology, University of California at San Diego, La Jolla, CA, VA San Diego Healthcare Systems, Medicine/Rheumatology Minneapolis VA Healthcare, Minneapolis, MN and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA, USA.

http://www.ncbi.nlm.nih.gov/pubmed/21372003

[extremrelaxer]

Antwort auf Beitrag Nr.: 41.153.855 von extremrelaxer am 06.03.11 07:01:04

@all: Ich habe gerade nochmals nachgeschaut, ob es wirklich diese Studie war.

Wir hatten die Studie am 20.12.2010 im Diskussionsthread besprochen. Beitrag Nr. 10420 ff

Damaliger Link: http://www.landesbioscience.com/journals/mabs/OwyangMABS3-1.…

mAbs 3:1, 49-60; January/February 2011; © 2011 Landes Bioscience
XOMA 052, a potent, high-affinity monoclonal antibody for the treatment of IL-1β-mediated diseases

Das angegebene Daten bzgl. e-publish "1. Januar" ist also nicht korrekt. Die Studie war definitiv schon Mitte Dezember 2010 online!

LG, ER

[extremrelaxer]

Zu Begründung meiner Hypothese, man könne evtl. mittels XOMA052 die Pathogenese des Diabetes mellitus rückgängig machen möchte ich noch folgendes Zitat aus dem Artikel aus dem "Islets" vom September / Oktober 2010 ins Bewußtsein rufen:

Mostly within the confines of a
cell culture system using the standard
insulinoma cell lines, MIN6 and INS-1,
IL-1β is shown to suppress the expression
of key β-cell transcription factors, including
MafA and Pdx-1;12 loss of these factors
inhibits β-cell development and/or function.
21,22 Additionally, IL-1β is shown to
stimulate NFκB activation, and NFκB
subsequently and directly induces the
expression of CHOP, thereby stimulating
apoptotic processes.

aus:
Defining the regulation of IL-1β- and CHOP-mediated
β-cell apoptosis
Nathan L. Vanderford
Markey Cancer Center; University of Kentucky; Lexington, Kentucky USA
Defining the regulation of IL-1β- and CHOP-mediated
β-cell …

Somit erwarte ich, dass es unter der IL-1-beta-Blockade mittels XOMA052 zum einen zum Stop der Apoptoseprozesse im Bereich der Betazellen kommt und desweiteren gleichzeitig eine Erholung der Betazellmasse und der Betazellfunktion einsetzt.
Mittels einer solchen Therapie könnte ich mir vorstellen, dass bei Anwendung kurz nach festgestellter Erstmanifestation eine Erholung der normalen Betazellfunktion möglich sein könnte.

[extremrelaxer]

Artikel zu Xoma und Servier in der weltweit renomiertesten wissenschaftlichen Zeitschrift: Nature

Nature Reviews Drug Discovery 10, 166 (March 2011) | doi:10.1038/nrd3390

Search Pubmed forDeal watch: XOMA and Servier to develop anti-IL-1β antibody for inflammatory diseases

Abstract
XOMA and Servier have agreed to jointly develop and commercialize the interleukin-1β (IL-1β)-targeted monoclonal antibody gevokizumab (XOMA 052) for the treatment of multiple inflammatory disorders. Following recent positive Phase II trial results, XOMA 052 has been granted orphan drug status by the US Food and Drug Administration (FDA) for Behçet's disease (BD), and the agent is currently undergoing Phase II trials in type 2 diabetes and cardiovascular disease.

To read this article in full you may need to log in, make a payment or gain access through a site license (see right).

http://www.nature.com/drugdisc/index.html
http://www.nature.com/nrd/journal/v10/n3/full/nrd3390.html


Da der Artikel kostenpflichtig ist, verweise ich nur auf die Seite von Nature und alternativ auf das Yahoo-Board: http://messages.finance.yahoo.com/Stocks_%28A_to_Z%29/Stocks…
Es geht um die multiplen Indikationen von XOMA052!

LG, ER

[extremrelaxer]

Demenz als weitere potentielle Indikation für IL-1-Blocker?
Positive Auswirkungen auf das Denk- und Merkvermögen im Tierversuch:

"The injection of interleukin-1β neutralizing antibody with lipopolysaccharide for 5 consecutive days resulted in the improvement of lipopolysaccharide-induced learning and memory deficits. These findings suggest that the expression of interleukin-1 plays an important role in lipopolysaccharide-induced activation of microglia and the associated functional deficits in learning and memory."

J Neurosci Res. 2011 Apr;89(4):506-14. doi: 10.1002/jnr.22582. Epub 2011 Feb 2.

Involvement of interleukin-1 in lipopolysaccaride-induced microglial activation and learning and memory deficits.
Tanaka S, Kondo H, Kanda K, Ashino T, Nakamachi T, Sekikawa K, Iwakura Y, Shioda S, Numazawa S, Yoshida T.

Department of Biochemical Toxicology, School of Pharmacy, Showa University, Tokyo, Japan. [e-mail].

http://www.ncbi.nlm.nih.gov/pubmed/21290410

[extremrelaxer]

IL-1-Blocker bei Myopathien?

"Inducible pro-inflammatory molecules, such as interleukin 1-β, may enhance the accumulation of stressor proteins. The principles for more effective treatment strategies are discussed"

Neuropathol Appl Neurobiol. 2011 Apr;37(3):226-42. doi: 10.1111/j.1365-2990.2010.01153.x.

Review: An update on inflammatory and autoimmune myopathies.
Dalakas MC.

http://www.ncbi.nlm.nih.gov/pubmed/21155862

[extremrelaxer]

Noch ein Artikel im Nature:

Review
Nature Reviews Immunology 11, 98-107 (February 2011) | doi:10.1038/nri2925

Type 2 diabetes as an inflammatory disease
Marc Y. Donath & Steven E. Shoelson

Abstract
Components of the immune system are altered in obesity and type 2 diabetes (T2D), with the most apparent changes occurring in adipose tissue, the liver, pancreatic islets, the vasculature and circulating leukocytes. These immunological changes include altered levels of specific cytokines and chemokines, changes in the number and activation state of various leukocyte populations and increased apoptosis and tissue fibrosis. Together, these changes suggest that inflammation participates in the pathogenesis of T2D. Preliminary results from clinical trials with salicylates and interleukin-1 antagonists support this notion and have opened the door for immunomodulatory strategies for the treatment of T2D that simultaneously lower blood glucose levels and potentially reduce the severity and prevalence of the associated complications of this disease.




http://www.nature.com/nri/journal/v11/n2/full/nri2925.html