When Novartis’ Cosentyx arrived in 2015 as the first next-gen psoriasis treatment in the United States, the med’s blockbuster status was assured. In fact, the drug reached that milestone during its first full year on the market.
But another guarantee came with the launch—competition and plenty of it.
Despite challenges, the drug has managed to stay ahead of its rivals by adding indications and satisfying doctors and patients along the way.
@LaraPo I wonder if a mesotherapy approach might be useful with this drug for skin aging? (for easier self-administration and also to avoid any possible systemic issues that might arise with simultaneous use with rapamycin):
The Novartis patent suggests:
Preferred forms for administration include forms suitable for parenteral administration , e . g . by injection or infusion , for example by bolus injection or continuous infusion .
Where the product is for injection or infusion , it may take the form of a suspension , solution or emulsion in an oily or aqueous vehicle and it may contain formulatory agents , such as as suspending , preservative , stabilising and / or dispersing agent . Alternatively , the antibody molecule may be in dry form , for reconstitution before use with an appropriate sterile liquid .
Once formulated , the compositions of the invention can be administered directly to the subject. The subjects to be treated can be animals . However , it is preferred that the compositions are adapted for administration to human subiects .
The pharmaceutical compositions of this invention may be administered by any number of routes including , but not limited to , oral , intravenous , intramuscular , intra - arterial , intramedullary , intrathecal , intraventricular , transdermal , transcutaneous ( for example , see WO 98 / 20734 ) , subcutaneous , intraperitoneal , intranasal , enteral , topical , sublingual , intravaginal or rectal routes .
Hyposprays may also be used to administer the pharmaceutical compositions of the invention . Typically , the therapeutic compositions may be prepared as injectables , either as liquid solutions or suspensions . Solid forms suitable for solution in , or suspension in , liquid vehicles prior to injection may also be prepared .
Direct delivery of the compositions will generally be accomplished by injection , subcutaneously , intraperitoneally , intravenously or intramuscularly , or delivered to the interstitial space of a tissue . The compositions can also be administered into a lesion . Dosage treatment may be a single dose schedule or a multiple dose schedule.
Looks like it can be administered in many different ways, including subcutaneously which is close to mesotherapy. Would be interesting to try. I’m currently using 3 pin nanosoft, 34 g, cartridges for intradermal injections. The depth is 1.2-1.5mm. Such needles are so thin (34g) that there’s no blood.
That’s interesting. If the inhibition was over 97% at 10 ng/mL then it’s probably quite significant also at 1 ng/mL, which is well within concentrations that people reach for a few days after taking typical doses of rapamycin for longevity.
They measured in blood. What I think we really want to know is how much IL-17 inhibition happens in the skin… wouldn’t we want a skin biopsy / tissue sample measure to better understand that. I don’t have much experience in this area - how representative is the blood measure, for skin measures?
Methods: Blood samples were drawn from 10 active VKH patients and 10 healthy individuals. PBMCs were cultured with or without anti-CD3 and anti-CD28 antibodies in the presence or absence of different concentrations of RAPA or DEX for 72 h
Full Research Paper here:
Inhibitory effect of rapamycin and dexamethasone on production of IL-17 and IFN-γ in Vogt–Koyanagi–Harada patients
But it also suggests that with whatever dosing levels of rapamycin that people are using, they are likely getting some skin anti-aging benefits along with other organ, etc. anti-aging benefits.
There are some companies offering blood tests for systemic IL-17 levels…
What I really wanted to find was a skin-level test that was commercially available. I found this paper on a skin biopsy method of evaluating IL-17 levels and it seemed to work when evaluating skin with psoriasis lesions, but not in regular skin … so it doesn’t sound like the IL-17 skin testing technology is quite where I’d like to see it.
I’ve been researching RAPA as a potential substitute for Methotrexate, which I take for psoriatic arthritis. MTX doesn’t work that well and has frustrating side-effects, thinning skin being one of them. Thank you for this information.
Th17 cells have recently emerged as a major player in inflammatory and autoimmune diseases via the production of pro-inflammatory cytokines IL-17, IL-17F, and IL-22. The differentiation of Th17 cells and the associated cytokine production is directly controlled by RORγt. Here we show that ursolic acid (UA), a small molecule present in herbal medicine, selectively and effectively inhibits the function of RORγt, resulting in greatly decreased IL-17 expression in both developing and differentiated Th17 cells. In addition, treatment with UA ameliorated experimental autoimmune encephalomyelitis. The results thus suggest UA as a valuable drug candidate or leading compound for developing treatments of Th17-mediated inflammatory diseases and cancer.
Yep, I think I will just stick to rapa to inhibit IL-17.
From the article you cite:
Both RAPA and DEX were able to significantly inhibit the production of IL-17 and IFN-γ by PBMCs from patients and healthy controls. RAPA was able to completely inhibit IL-17 production at a dosage of 10 ng/ml but only partially suppressed IFN-γ production even at a much higher concentration (1000 ng/ml). DEX inhibited the production of both IL-17 and IFN-γ by approximately 70%.
Conclusions: This study indicates that both RAPA and DEX inhibit the production of IL-17 and IFN-γ by PBMCs. RAPA is much stronger in inhibiting the production of IL-17 than DEX.
Interesting comments by “Reason” of Fight Aging, seems to confirm the idea that trying to target just the skin may be a winning approach with this IL-17 protein and the existing drugs that can be used to inhibit it. At some point in the not too distant future I think I’d like to try the mesotherapy approach that @LaraPo has described in the past, using the existing IL-17 inhibitor drugs that were mentioned earlier in this thread. Perhaps this might also work with micro-needling approaches on the scalp for hair regrowth and repigmentation.
The researchers show that blocking IL-17 slows the manifestations of skin aging. The challenge in this sort of approach is that inflammatory signal molecules are needed for the normal immune response to function correctly. The treatment of autoimmune conditions via blockade of various inflammatory signals has meaningful side-effects that include suppression of necessary immune responses. This is less of a concern if treatments target only the skin, but we should hope that researchers can identify more targeted, subtle ways to eliminate only excess inflammatory signaling in the rest of the aging body.
