Everyone is happy with our FDA update today, even though the market may or may not fully understand the significance (yet), but hey, a green 6.67% is better than nothing.
I came a cross a few interesting articles in the past few days. It all started off with Asthma and then I got side tracked:
Cell therapy for lung disease
Abstract
Besides cancer and cardiovascular diseases, lung disorders are a leading cause of morbidity and death worldwide. For many disease conditions no effective and curative treatment options are available. Cell therapies offer a novel therapeutic approach due to their inherent anti-inflammatory and anti-fibrotic properties. Mesenchymal stem/stromal cells (MSC) are the most studied cell product. Numerous preclinical studies demonstrate an improvement of disease-associated parameters after MSC administration in several lung disorders, including chronic obstructive pulmonary disease, acute respiratory distress syndrome and idiopathic pulmonary fibrosis. Furthermore, results from clinical studies using MSCs for the treatment of various lung diseases indicate that MSC treatment in these patients is safe. In this review we summarise the results of preclinical and clinical studies that indicate that MSCs are a promising therapeutic approach for the treatment of lung diseases. Nevertheless, further investigations are required."
It then lists diseases such as ARDS, on which we recently got a Cynata
update:
"In April 2017, Cynata reported a collaboration with the Critical Care Research Group to investigate Cymerus MSCs as a treatment for acute respiratory distress syndrome (ARDS). The pre-clinical trial, which will be conducted in association with the Prince Charles Hospital in Brisbane, will evaluate the effectiveness of Cymerus MSCs in sheep with ARDS which are currently supported by extracorporeal membrane oxygenation (ECMO). If successful, Cynata anticipates the data will support progression into a clinical trial in humans with ARDS undergoing ECMO support."
The article states the following:
"ARDS mortality rates remain as high as 20–40% [
24], thus, novel therapeutic approaches are needed. MSCs have proven to be efficacious in various animal models. Curley
et al. [
17] demonstrated that treatment of rats with human umbilical cord (uc)MSCs in a model of
Escherichia coli-induced ARDS resulted in a reduction of disease severity as determined by prolonged survival, improved oxygenation and a decrease in inflammatory parameters such as a reduced alveolar infiltration of neutrophils, decreased bronchoalveolar lavage (BAL) levels of IL-6 and TNF-α and increased levels of the anti-inflammatory proteins IL-10 and TNF-stimulated gene 6 protein. The same significant amelioration of pulmonary inflammation, reflected by reductions in neutrophil counts in BAL fluid and reduced levels of proinflammatory cytokines was observed using syngeneic MSCs in a murine model of lipopolysaccharide (LPS)-induced ARDS [
18]. Interestingly, administration of MSCs genetically modified to express the vasculoprotective protein angiopoetin-1 additionally resulted in nearly complete reversal of LPS-induced increases in lung permeability in the same study."
- it basically means that if all goes as planned, our "Cynata sheep" should deliver very positive pre-clinical results!
It also mentions IPF (Idiopathic pulmonary fibrosis):
"Due to limited treatment options, the prognosis is often poor with a median survival time of ∼3 years after diagnosis [
30]. Therefore, novel therapies are under investigation."
"In this model, early administration of bmMSCs or ucMSCs during the initial inflammatory phase resulted in a protective effect: reduced levels of proinflammatory cytokines, decreased deposition of activated fibroblasts and collagen and improved epithelial repair. However, no therapeutic or profibrotic effects were observed when treated in the subsequent fibrotic phase [
26–
28]. Compared to the treatment with the anti-fibrotic and anti-inflammatory drug pirfenidone,
i.v. injection of human aMSCs was more effective in ameliorating bleomycin-induced lung fibrosis [
29]. Further improvement of the protective effects of MSCs on pulmonary function, inflammation and fibrosis were observed with hypoxic pretreatment of MSCs by increased secretion of anti-inflammatory, anti-apoptotic and anti-fibrotic factors upon hypoxic treatment".
- I read that as maybe worthwhile having a look eventually
The most interesting disease listed is COPD (Chronic obstructive pulmonary disease)!
Our recent pre-clinical Asthma results showed "
statistically significant improvements in the three main features of asthma: airway inflammation, airway remodelling and airway hyperresponsiveness (AHR)."
Back to the article:
"MSC-based products have been studied extensively in animal models of COPD due to their tissue-regenerative and immunomodulatory properties."
"Human bone marrow-derived (bm)MSCs reduced fibrosis as analysed by histological scoring of lung sections using the Ashcroft scale; apoptosis as measured by a reduction of DNA strand breaks; and inflammation as seen by a reduction of interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α levels in an elastase-induced mouse model of COPD [
10]. Interestingly, findings from our own laboratory indicate that the efficacy of bmMSCs in this model can be improved further if the cells are genetically modified to express the potent protease inhibitor α1-antitrypsin [
37,
38] (S. Geiger, unpublished data)."
- keep that "genetically modified bit in mind for a moment, please
"A recent study found that
human induced pluripotent stem cell-derived MSCs were more effective than bmMSCs in ameliorating cigarette smoke-induced inflammation in rats by reducing neutrophil and macrophage infiltration"
- that's me underlining it for obvious reasons lol
Now, here's the twist:
Article starts off with "Besides cancer"
- we recently had
apceth returning the licencing rights in oncology, however stating that they are very happy with the results
It then lists the potentials in treating lung diseases, e.g. COPD and IPF
- both happen to be
therapeutic areas that apceth is currently developing engineered MSCs for
- we then take a look at the authors
Sabine Geiger,
Daniela Hirsch &
Felix Hermann
- yeah, all working for apceth
The genetically engineered MSCs they are talking about in the article
-
apceth is the patent applicant
An article in the
Cytotherapy Journal has been published (wasn't able to access it just yet), but the introduction sounds very promising:
"In conclusion, the present study provides the first in vivo proof of concept for the treatment of emphysematous COPD with AAT-MSCs."
- 5 of 8 authors work for apceth, one of them being Dr Christine Günther, the apceth CEO herself
Sounds to me as they have refined their
therapeutic focus now or are at least far advanced.
Anyone care to take a guess what the mysterious "
option to non-exclusive rights to other disease target areas" are?
Sounds like the answer to that question is not too far off!
(20min delay)