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arjay

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19/02/21

22:28

Post #: 51172826
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Originally posted by monti901 ↑

From BioPharma investing today...

Antisense Therapeutics (ANP.AX)
It’s going to be an interesting few months ahead for those involved with Antisense therapeutics, with news that they are going after new disease indications for their CD49d antisense inhibitor, and $10m in the bank. The list of potential diseases with applicability is broad, but pharmacokinetics and clinical relevance are two things to keep in mind. However they’ve got an valuable set of MS patient data which demonstrates efficacy of some sort as well as a level of safety to fall back on at a much higher dose than they are currently playing with. On the DMD front, Sarepta’s recent fall in value of ~$6bn USD on the back of missed primary endpoints confirms a suspicion that many hold - dystrophin replacing gene therapies can’t be efficacious at least in their current states. It is likely that the initial insults of myocyte necrosis during muscle contraction kick start an inflammatory process which doesn’t notice if you’ve replaced a certain level of dystrophin.
Here is some evidence that VLA-4 be a useful target:
• Higher levels of VLA-4 expressed on T-cells are found in severely progressing DMD patients — with a prospective study demonstrating that high expression is a biomarker that can be used to predict disease progression.
• Both CD4 and CD8 T-cells have been demonstrated to be responsible for a majority of the muscle damage associated with Duchenne’s — mdx mice were depleted of CD4 and CD8 T-cells separately, and both cases demonstrated significantly reduced muscle pathology (over 50%).
• Splenocyte transfer from mdx mice into wild type mice induces muscle necrosis
• Osteopontin (OPN) is another ligand of VLA-4, encoded by the SPP1 gene, which is heavily upregulated in DMD (over 100 fold). Mutations in this gene thought to increase constitutive levels of OPN are associated with around a 1-2 year earlier loss of ambulation.
• Similarly, fibronectin is upregulated in DMD muscle too, and it is also a ligand for VLA-4.
• Corticosteroids remain the only validated therapy and they lower leukocyte infiltration into muscle
• T-cells extracted from DMD patient muscle biopsies demonstrated V-segment restriction
• Questionable correlation between the force or rate of muscle contraction and the progressive degeneration that results. Certain muscles are spared, non-dominant hand loses function at a rate that is comparable to the dominant hand suggesting some systemic inflammatory process being responsible.

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Yes I got an email...nice work Monti..

ANP Price at posting: 18.5¢ Sentiment: Buy Disclosure: Held
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