Three questions to Professor ?dum – on cutaneous T-cell lymphoma and the potential role of endolysin XZ.700* in development of a treatment

On Wednesday March 8, Micreos shared the positive positive results of an investigational study: Endolysin inhibits skin colonization by patient-derived Staphylococcus aureus and malignant T cell activation in cutaneous T cell lymphoma, published in the Journal of Investigative Dermatology ?(https://doi.org/10.1016/j.jid.2023.01.039).

The study was led by Niels ?dum of the University of Copenhagen’s Skin Immunology Research Centre, and we asked him a few questions on the study and its potential impact on the development of a treatment for cutaneous T-cell lymphoma.?

Why is CTCL so difficult to?cure, leaving patients with few or no sustainable treatment options?

For two reasons. First, because we don't know precisely what causes the disease.

Second, because we do know that it is a multi-factorial disease – i.e. that the disease involves both genetic events, such as mutations, chromosomal changes or other, and environmental factors, such as bacteria, being involved in the disease activity and progression.

How can these findings on XZ.700* prove to be important in the development of a treatment for CTCL?

In two ways. First, patient skin lesions often harbor Staphylococcus aureus (S. aureus), which can elicit skin inflammation and fuel disease activity. By selectively targeting S. aureus, XZ.700* has the potential to both eradicate the bacterium and its bad effects on disease activity and progression.

This is a new approach to eliminate an important external factor that aggravates the disease. Therefore, endolysins such as XZ.700* could add a new therapeutic option for doctors to treat CTCL, which is expected to work well together with classical anti-cancer treatments, providing a more holistic approach to the treatment of these patients.

Second, the endolysin XZ.700* provides an entirely new possibility to prevent S. aureus from colonizing susceptible skin lesions in the first place.

In addition, it selectively targets the "bad" S. aureus without harming the "good" bacteria, that protects the skin, which potentially make endolysins such as XZ.700* ideal for preventive care of CTCL patients.

How could this have an impact on the use of antibiotics considering the rising impact of antibiotic?resistance?

We know that aggressive antibiotic treatment eliminates S. aureus and has a beneficial effect on disease activity in the patients. However, long-term treatment and prophylactic use of antibiotics pose many serious problems and risks.

First, antibiotics pose the risk of serious allergic reactions and other severe side effects. Second, many patients already harbor multi-resistant staphylococcus aureus (MRSA), and therefore will not benefit from antibiotics.

Long-term treatment with antibiotics may also hamper the possibility for later treatment of life-threatening S. aureus infections like sepsis. Also, antibiotics do not specifically target the bacterium in question but a broader spectrum of bacteria. Antibiotic treatment therefore disrupts the normal flora – both in the gut and the skin - which may cause unwanted intestinal problems and damage the normal skin homeostasis.

On top of this, long-term use of antibiotics comes with the risk of inducing antibiotic resistance, which is already a global challenge to the medical treatment of infections. It is therefore extremely important to develop novel antimicrobial treatments that selectively kill S. aureus without harming the "good" bacteria, and without the problems associated with antibiotics. It is therefore so exciting that the endolysin XZ.700* efficiently kills patient-derived S. aureus and potentially blocks their cancer-promoting effect.

As there is an unmet need for antibiotic-free treatment and prevention of S. aureus in CTCL, endolysins such as XZ.700* therefore have a great potential for antimicrobial treatment and prophylaxis without the concerns of resistance in CTCL (and other skin diseases where S. aureus are involved).

*About MEndoC

Based on pre-clinical models and increased intrinsic activity, Micreos has moved the development program in CTCL from XZ.700 to the next generation endolysin, namely MEndoC.