Been going through the FASEB article and there are a few parts I would like to quote. I will also highlight a few words (bold and/or underline) to emphasise on what I (in my opinion) consider important.
First of all, this article is talking about a market, that is expected to reach US$25.6 billion by 2024! That's the big league compared to GvHD.
(all quotes "" are from the above mentioned FASEB article)
I've asked relevant entities for permission to post some excerpts! Please note, that further work is necessary to validate the following statements!
"Asthma is a chronic respiratory disease affecting about 300 million people worldwide and is attributed to 250,000 annual deaths" - remember our pre-IND meeting with the FDA, which "also include" GvHD? I wonder what other diseases have been included in the discussion... haha... RMAT/breakthrough... just putting it out there)
"Current asthma therapy, including corticosteroids and b-agonists, is focused on symptom management rather than disease regression and is therefore not fully effective" - that's a hell lot of money to target the symptoms rather than the actual disease...
"The gold-standard therapy of corticosteroids is also ineffective in treating the severe and severe-refractory subpopulations of patients with asthma. Patients with severe asthma often need treatment with high doses of corticosteroids that can be associated with systemic side effects (7) and do not necessarily improve lung function or quality of life (8, 9). Additionally, the severe refractory subgroup of patients with asthma shows fixed airway restriction (7), and therefore this population displays the critical role of AWR as part of their asthma symptoms, highlighting an urgent need for treatment strategies that can target and reduce AWR." - I believe that's what the study conducted by Professor Samuel's group is comparing our MSCs with right now, corticosteroids. If our MSCs now perform the same way as in the initial trial when directly compared with the "gold-standard therapy"... it's ON!
"Compared with corticosteroids, which suppress AI, MSCs have been shown in these models to actively reduce the presence and activity of the cells responsible for inflammation.
Furthermore, MSC treatment has been shown to reduce epithelial thickness, smooth muscle hyperplasia, and goblet cell metaplasia in the airways (21). MSCs modestly decrease subepithelial and total collagen deposition (fibrosis) through their ability to promote collagen-degrading gelatinase levels (15), suggesting that MSCs also have antiremodeling actions. However, MSCs have not consistently demonstrated the ability to relieve the adverse symptoms associated with chronic disease settings, and the outcomes of MSC treatment can vary depending on their tissue origin/source, extent of culture expansion, donor-dependent viability and efficacy, and the timing of their administration (3, 22–24). This has likely contributed to the slow progression toward the clinical utility of MSCs from various sources for their therapeutic and tissue-reparative functions (25). Additionally, because only a relatively small number of MSCs can be isolated from each donor organ, a continuous supply of donors would be needed to facilitate sufficient numbers for experimental and commercial use." - talking about first-generation sources of MSCs
"Our current findings that MCA-MSCs, particularly when delivered intranasally [IN] to the allergic airways/lungs of mice, could markedly suppress AI (by about 75%) and goblet cell metaplasia (by about 50%) suggests that they mediate greater immunomodulatory properties compared with MSCs derived from the human bone marrow (15, 16) or adipose tissue (36)."
"asthma therapy should target the epithelium. When administered through IV injection, MCA-MSCs did not significantly affect the OVA-induced epithelial thickness. However, IN delivery of these cells resulted in a decreased epithelial thickness, despite both routes of delivery offering similar reductions in AI. This contrasts with previous findings related to bone marrow–derived MSCs in which the IN delivery of bone marrow MSCs alone had no effect on epithelial thickness (15). In that study, epithelial thickness was not affected by a decrease in AI. Hence, the difference observed between MCA-MSCs and bone marrow MSCs appears likely due to an active property of MCA-MSCs rather than being a passive effect produced by their ability to attenuate AI. Furthermore, in another study the administration of an epithelial factor repair peptide (trefoil factor-2) reduced epithelial thickness to the same extent as combination treatment with an antifibrotic and a corticosteroid, despite a greater decrease in AI offered by the combination treatment (41). As such, the reduction in epithelial proliferation was not mediated by a reduction in inflammation. With this additional evidence, the findings of our study may suggest either that the direct delivery of MCA-MSCs into the lung allows sufficient accumulation of paracrine factors that reduce epithelial thickness, or that these cells to come into direct contact with the damaged epithelium and mediate a reversal in its proliferation. This decrease in the epithelial thickness (and goblet cell metaplasia) provides the first piece of evidence of the ability of these MCA-derived MSCs to reverse AWR." - ticked
Although IV delivery of MCA-MSCs significantly reduced both aberrant subepithelial and total collagen deposition, IN delivery of these cells completely reversed this aberrant collagen deposition back to the levels seen in the uninjured saline-treated group. These results were unexpected because previous studies from our laboratory showed that the OVA-induced promotion of subepithelial and total collagen deposition could only be fully reversed when stem cell–based treatments were coadministered with serelaxin, an antifibrotic, hormone-based drug" - ticked, more than that actually, as they only managed to get these results with a combined treatment of stem cell-based product plus drug. Something revolutionary could be on the horizon... haha
"Hence, IN delivery of MCA-MSCs could have similar effects to serelaxin or possess antifibrotic properties similar to fetal fibroblasts, which can facilitate wound healing in the absence of fibrosis (47). Further work is required to validate these hypotheses." - happy to wait for that
"The key finding of this study was that MCA-MSCs, when given intranasally, reversed fibrosis and reverted AHR to levels measured in uninjured mice." - ticked
"In our study, it is likely that these MCA-MSCs corrected AHR by targeting AWR at a number of levels, in addition to their anti-inflammatory effects.
In summary, the present study, the first on MCA-MSCs in chronic AAD, found that MCA-MSCs could effectively reduce AI and reverse markers of AWR as well as AHR. Therefore, MCA-MSCs may provide a novel stand-alone therapy or an adjunct therapy for subpopulations of asthma sufferers who do not respond to current (corticosteroid) therapy." - BOOM!!!
CYP Price at posting:
65.0¢ Sentiment: Buy Disclosure: Held
(20min delay)