The Blueprint Revisited

From the thread The Blueprint:
"Here's the question. Does ATL1102, in a similar manner to the anti-CD49d mAb, decrease the level of activated lymphocytes while simultaneously increasing the level of regulatory T cell lymphocytes? That would be a win-win situation."

Ever wondered why the 25 mg per week dosage has made it into the ball park. It was the rate the FDA had approved in MS for a future trial but frankly we all thought it would serve only the limited function of proving safety and tolerability in DMD. We may finally end up with a higher therapeutic dosage rate, but at 25 mg per week something has dramatically gone right.

I previously asked the question whether ATL1102 may be doing more than intended because it wasn't acting alone. Is it indeed possible that ATL1102 is harnessing the natural power of regulatory T cells (Tregs) simply by altering the balance of lymphocyte sub-populations. Tregs stand down activated T cells in the system of checks and balances in the immune system and quieten inflammation.

There is another scenario that is helpful in shedding light on the potential power play at work in inflammation. In some cancers its necessary to turn a cold tumor microenvironment to hot in order to attract T cells to attack the tumor. In DMD, it is arguably the case that the reverse is true. We need to turn a hot inflammatory microenvironment to cold. There is a plausible hypothesis that ATL1102 does act to decrease the level of activated lymphocytes (CD49dhi T cells) while simultaneously increasing the level of regulatory T cell lymphocytes (CD49dlow T lymphocytes or Tregs). Is that why the total effect is greater than the sum of the parts given the low dosage rate?

We will find out by testing for any increases in Tregs following administration of ATL1102. Restoring balance could be as instrumental in the therapeutic impact of the drug as inhibiting CD49d. The implication for the treatment of inflammation is profound. ATL1102 could change the therapeutic landscape for DMD, MS and any number of disease indications where inflammation is part of the problem rather than the solution.