ED is considered a general indication of decreased male health and is estimated to affect approx. 340 million men worldwide (1). Around 40% of European men between the age of 40 and 79 suffer from ED. Prostate cancer is the most common cancer in men worldwide, and 50% or more suffer from ED after prostatectomy (2). The incidence of ED is on a constant rise, since the main drivers of ED are age, prostate cancer and diabetes, all conditions that are drastically increasing worldwide. As of today, treatment modalities for ED including PDE-5 inhibitors and prostaglandins, are symptomatic and palliative but not causative and in addition have substantial side-effects (2). Current symptomatic treatment medication needs to be taken for the rest of the patient’s life, as none of the treatments can restore the original organ function. The disease’s impact on quality of life, morbidity and mortality are representative for concomitant increasing health care costs for society and the desperate and imperative need for novel treatment strategies. There is thus a large unmet clinical need for novel treatment modalities. Taking into account the limitations and dropout rate of current medical treatments, regenerative approaches like Blue Cell therapy represent a promising alternative. Developing immunomodulatory and regenerative cell therapies for ED and lymphedema would fundamentally reduce the burden of these chronic diseases on public healthcare systems and improve life quality of affected patients dramatically.
(1) Yafi, F.A., et al., Erectile dysfunction. Nat Rev Dis Primers, 2016. 2: p. 16003.
(2) Carvalheira, A.A., et al., Dropout in the treatment of erectile dysfunction with PDE5: a study on predictors and a qualitative analysis of reasons for discontinuation. J Sex Med, 2012. 9(9): p. 2361-9.
(3) Haahr, M.K., et al., Safety and Potential Effect of a Single Intracavernous Injection of Autologous Adipose-Derived Regenerative Cells in Patients with Erectile Dysfunction Following Radical Prostatectomy: An Open-Label Phase I Clinical Trial. EBioMedicine, 2016. 5: p. 204-10.
ERECTILE DYSFUNCTON TREATMENT
The rationale for using Blue Cells to treat ED is based on these progenitor cells ability to modulate the immune system by inhibiting inflammation while stimulating regeneration. In addition, the Blue Cells stimulate repair of endothelial cells, vascular smooth muscle cells and neurons. The mechanism behind penile erection is that blood fills the penile sinusoids by relaxation of vascular smooth muscle cells induced by release of nitric oxide (NO) from the cavernous nerves and endothelial cells. NO diffuses into the vascular muscle cells, activates guanosine cyclase to produce cGMP, which in turn reduces Ca2+ levels and induces relaxation.
After prostatectomy, the penile nerves exhibit a form of neuropraxia leading to reduced NO release and ED. The nocturnal erections result in an oxygen burst (PO2 peak) that plays an important role in nourishment of the penile tissue. Lack of the nocturnal erections leads to fibrosis of penile tissue and apoptosis of endothelial cells in the cavernous sinuses, resulting in even lower NO release and permanent ED. Our data suggests the Blue Cells restore the penile NO release since levels of endothelial NO Synthetase (eNOS) increases. At Odense University Hospital in Denmark, we have just completed treatment of 70 patients in a prospective, randomized, placebo-controlled and double-blinded phase II clinical trial using autologous ADRC’s for erectile dysfunction after prostate cancer. Accordingly, 35 men received ADRC’s while 35men were injected with saline. Prostate cancer is the most common cancer in men, and 16-60% experience ED after radical prostatectomy. The Danish Medicines Agency and the National Ethical Counsel have approved the current trial based on preliminary data from our phase 1 study that describes a stem cell therapy that appears safe and potentially can correct ED after prostatectomy (3). In this ‘first in human’ study, we found that 8 out 11 men completely regained the erectile function after ADRC treatment although they had ED for one year or more after a prostatectomy. This is a quite remarkable result since patients had no effect of PDE-5 inhibitors like Viagra before ADRC treatment.