Replies to post #124701 on Anavex Life Sciences Corp (AVXL)

[Investor2014]

So is Teva or Celgene more likely going to be our MS partner?

Celgene

SUMMIT, N.J.--(BUSINESS WIRE)-- Celgene Corporation (NASDAQ:CELG) today announced that its phase III RADIANCE trial, evaluating the efficacy and safety of ozanimod, an investigational oral, selective S1P 1 and 5 receptor modulator, in patients with relapsing multiple sclerosis (RMS), met the primary endpoint in reducing annualized relapse rate (ARR), compared to weekly interferon (IFN) ß-1a (Avonex®).

http://ir.celgene.com/releasedetail.cfm?releaseid=1027283


Teva

Our work in MS is not confined to Copaxone® and the relapsing forms of MS. Patients with progressive forms of the disease currently have no approved treatment options. We have an extensive research program investigating a new compound called laquinimod, which we believe has a neuro-protective capability. We are developing laquinimod for both relapsing and progressive forms of MS, in the hope that this new potential medicine will offer patients a much needed option in the treatment of progressive forms of MS.

http://www.tevapharm.com/research_development/rd_focus/multiple_sclerosis/

No reference to Biogen in the Lisak et al Abstract!

[neiu]

Nice. Thanks!

It's going be a wild ride going into 2018

[rocalinda]

Thanks for posting.

Wow!!!

[blu_1]

Could you provide a link please?

[plexrec]

I've read the abstract and it sounds great--yet not being a scientific guy---could someone explain in layman's language--what we have here--what it all means re: A 2-73 and MS====Thanks

[attilathehunt]

Investor - You stated Ladies and Gentlemen, it works!"

Thank you for starting with that quote!! I read the abstract and it sounds positive for A2-73 but can you or others pontificate in laymen terms how big this really is?

Now with this "It Works" abstract and WSU being independent and coupled with the fact Biogen relies on WSU, should I dare say that a deal with Biogen is imminent? This would explain MS "disappearing" from the pipeline chart.

[Turner2017]

Awesome news, thank you for the info

[polarbear77]

Thanks investor2014 for posting this WSU/MS abstract this morning.

If I were afflicted with MS, I believe that I would be both excited & encouraged after reading this independent abstract.

If I were a BP heavily invested in the MS space, I believe that I would be both antsy & desirous after reading this independent abstract.


Excerpted
“Results: We found that ANAVEX2-73 inhibited death of OL, OPC and Neu induced by the toxic factors and confirmed that DM also protected Neu as well as OL and OPC. Pretreatment of cultures with S-1R antagonist BD1047 inhibited the protection provided by both ANAVEX2-73 and DM. As reported earlier for DM, ANAVEX2-73 increased OPC proliferation assessed by uptake of a uridinie analog (BrdU). ANAVEX2-73 differed from our published findings with DM as it also increased maturation of OPC to more mature OL based on expression of phenotypic markers.
Conclusions: ANAVEX2-73 and DM protect OL, OPC and Neu from several toxic molecules involved in pathogenesis of MS. Protection appears to be dependent on signaling through S-1R. Both ANAVEX2-73 and DM increase OPC proliferation. ANAVEX2-73 also accelerates OPC maturation to OL. S-1R agonists could provide both protection and help with repair in MS.”

http://www.professionalabstracts.com/ectrims2017/iplanner/#/grid

“From the planner 27th Oct, Hall B at 14:00-15:30
Parallel Session 14: Remyelination: from biology to clinical trials”

[McMagyar]

so thanks again Investor!
Lisak IS the MAN when it comes to MS..the Dr!

still reviewing time frame for first in mouse studies(how long they have taken in past..ran out of time this morning)


Quote:
238 - Sigma 1 receptor agonists as potential protective and reparative therapy in multiple sclerosis
R.P. Lisak, L. Nedelkoska, J.A. Benjmains Neurology, Wayne State University School of Medicine, Detroit, MI, United States
Objectives: Determine if sigma-1 receptor (S-1R) agonists can provide protection for oligodendrocytes (OL), OL precursors (OPC) and central nervous system (CNS) neurons (Neu) and promote repair. Background: S-1R are endoplasmic reticulum (ER) chaperones upregulated during ER stress, and also regulate calcium homoeostasis via inositol triphosphate at the ER-mitochondrial interface. We reported that dextromethorphan (DM), a S-1R agonist and weak NMDA receptor (NMDAR) antagonist, protects OL and OPC from toxic effects of molecules important in the pathogenesis of multiple sclerosis (MS) and increases OPC proliferation. Other groups have found inhibition of an animal model of MS by DM and another S-1R agonist. We sought to examine the potential protective and reparative effects of ANAVEX2-73, also a S-1R agonist, an NMDAR antagonist and a weak muscarinic agonist, unrelated to DM, on OL, OPC and Neu and extend our studies of DM to Neu. For both ANAVEX2-73 and DM we investigated if protection was due to agonism of S-1R.
Methods: Cell cultures containing >90% OL, OPC or Neu were prepared from neonatal rats and were incubated with staurosporine (apoptosis), glutamate (excitotoxicity), H2O2 (reactive oxygen species; ROS), quinolinic acid (inflammation) or additional medium (control) with or without DM or ANAVEX2-73 (provided by ANAVEXTM Life Sciences Corp, under the SIGMACEPTOR (R) program). Neu cultures were incubated with the same toxic molecules with/without ANAVEX2-73 or DM. We incubated OPC with ANAVEX2-73 and evaluated proliferation as well as maturation.
Results: We found that ANAVEX2-73 inhibited death of OL, OPC and Neu induced by the toxic factors and confirmed that DM also protected Neu as well as OL and OPC. Pretreatment of cultures with S-1R antagonist BD1047 inhibited the protection provided by both ANAVEX2-73 and DM. As reported earlier for DM, ANAVEX2-73 increased OPC proliferation assessed by uptake of a uridinie analog (BrdU). ANAVEX2-73 differed from our published findings with DM as it also increased maturation of OPC to more mature OL based on expression of phenotypic markers.
Conclusions: ANAVEX2-73 and DM protect OL, OPC and Neu from several toxic molecules involved in pathogenesis of MS. Protection appears to be dependent on signaling through S-1R. Both ANAVEX2-73 and DM increase OPC proliferation. ANAVEX2-73 also accelerates OPC maturation to OL. S-1R agonists could provide both protection and help with repair in MS.
Disclosure:
Robert Lisak: Grant funding from Teva, Speakers List: Teva; Consulting: Teva, Syntimmune, Celgene and RedHill Biopharm.
Liljana Nedelkoska: Nothing to disclose
Joyce Benjamins: Nothing to disclose
Research funded by the Parker Webber Chair in Neurology, Wayne State University/DMC Foundation. ANAVEX2-73 supplied by ANAVEXTM Life Sciences Corp.