S epidermidis Lipotechoic Acid (SELTA) for Immune Modulation

NU 2014-062

INVENTORS
Stephen F Murphy
Praveen Thumbikat*
Anthony Schaeffer
 
SHORT DESCRIPTION
A bacterial cell wall component to treat chronic pelvic pain syndrome.

BACKGROUND
Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) is a common debilitating disorder characterized by pelvic pain and lower urinary tract symptoms. However, due to limited understanding of its etiology, the development of effective treatments has been hampered.  There is evidence that inflammatory and autoimmune mechanisms may play a role and, more specifically, that there may be a role of pathogenic bacteria.  Chronic pelvic pain syndrome has been modeled using murine experimental prostatitis (EAP), in which a subpopulation of T cells has been shown to play a critical role in disease initiation and development of pelvic tactile allodynia.

ABSTRACT
Using the EAP murine model, Northwestern researchers have identified that the intraurethral introduction of a specific S. epidermidis strain results in reduction of pelvic pain due to the modulation of T-cell immunity.  This finding led researchers to investigate whether the immunodulatory properties of the bacteria helps prevent or protect pathogenic infections via inflammation reduction.  The researchers identified that a component of the bacterial cell wall, lipotechoic acid (LTA), was directly responsible for the decrease in pain. Injection of purified S. epiderdimidis LTA (SELTA) into the prostates of EAP mice led to 50% reduction in pain levels for up to 7 days, similar to whole bacteria treatment. Quantification of T-cell activation using flow cytometry showed that LTA reduces pain through immune modulation. Compared to non-treated EAP mice, the prostates of S. epidermidis or LTA-treated EAP mice had increased the levels of T-regulatory cells, counteracting T-cell-driven inflammation. These results identify a new potential therapeutic role for SELTA  in the treatment of prostatitis-associated pain.

APPLICATIONS

• Therapeutic for pelvic pain related to prostate inflammation in CP/CPPS patients
• Induction of immune tolerance in autoimmune diseases associated with high levels ot T-cell mediated inflammation, like rheumatoid athritis, multiple sclerosis and inflammatory

    
ADVANTAGES

• Unparalleled level of symptom reduction which has not been observed with any other monotherapies in CP/CPPS patients
• Specificity to prostatic inflammation with no systemic effects
• Inflammation-associated immunomodulatory effects

PUBLICATIONS
Murphy SF, Schaeffer AJ, Done JD, Quick ML, Acar U and Thumbikat P. (2018) Commensal bacterial modulation of the host immune response to ameliorate pain in a murine model of chronic prostatitis. Pain. 158(8):1517-1527.
Murphy SF, Hall C, Done JD, Schaeffer AJ and Thumbikat P. (2018) A prostate derived commensal Staphylococcus epidermidis strain prevents and ameliorates induction of chronic prostatitis by UPEC infection. Sci Rep. 8(1):17420

IP STATUS
US and International patent applications have been filed.

In a murine model of experimental autoimmune prostatitis (EAP), closely mimicking human chronic prostatitis/chronic pelvic pain syndrome, treatment with LTA significantly decreased tactile allodynia responses compared to untreated, EAP mice.