Monoclonal Antibodies to the Rescue: How Biologic Therapies Can Relieve Symptoms of Psoriasis
In ancient times, tzaraath, translated from the Hebrew Bible, was a catch-all phrase for a variety of skin conditions that likely included psoriasis. When the person was in his or her “afflicted phase,” the patient was described as “impure.”1 Now we know that 2-3% of the population suffers from the condition that has nothing to do with impurity and everything to do with a combination of genes and “specific external factors” known as triggers.2 These triggers can include stress, injury to the skin, infection or certain medications that lead to an alteration in the life cycle of skin cells.
Though there is no cure for psoriasis, there are a variety of strategies that research firms can employ in order to develop effective treatments. New biologic drugs can target specific components of the immune system to alleviate symptoms of psoriasis, with two in particular that revolve around the development of monoclonal antibodies directed against specific cellular components:
Block T cell activation: Inflammatory components present in psoriatic lesions are defined in part by an increased level of activated T cells.3 When pathogenetic T cells enter the skin, researchers have also found that they release a number of cytokines and chemokines that attract other immune system cells to the region resulting in increased inflammation. Removing activated T cells and/or preventing T cell activation through the creation and development of monoclonal antibodies is an important component of successful treatment in psoriasis.4 This could be achieved by creating monoclonal antibodies that target common regions of activated T cells to increase the ability of biologics to bind to these cells to prevent their activation.
Block proteins: T cell activation results in a cascade of immune system proteins and inflammatory components that can worsen symptoms of psoriasis. In order to prevent these proteins from worsening a patient’s disease state, biologic therapies can be directed to inhibit these secondary proteins. For example, monoclonal antibodies directed against proteins such as tumor necrosis factor-alpha (TNF-alpha), interleukin 17-A or interleukins 12 and 23 might alleviate some of the extra inflammation associated with T cell activation5 are already being used to inhibit the inflammatory cascade present in psoriasis.
Killing Two Birds With One Stone: Biologics Research Can Pave the Way for New Therapies
Beyond targeting components of the immune system that can lead to an immediate relief from symptoms of psoriasis, the use of biologics can pave the way toward (1) understanding skin biology and (2) discovering even better targets beyond the abovementioned proteins or T cells. For example, scientists have long known that skin stem cells constantly regenerate.6 But how do existing biologic therapies affect the rate or characteristics of regeneration?
To understand this process, researchers can culture skin cells derived from normal individuals and those affected by psoriasis and test how various monoclonal antibodies affect the proliferation and properties of cultured skin stem cells in the two conditions.7 If the biochemical, metabolic and morphological changes that occur in normal and diseased states are carefully recorded, studying this data set could present novel mechanisms for new therapies and monoclonal antibodies that may differ significantly from what we have today.
BIOVIA’s Biologics Solution offers a suite of effective tools for both developing treatments based on current understanding (i.e. targeting T cells or immune system proteins), while also organizing the data that could elucidate new targets. By offering software that helps with planning, executing and interpreting experimental data, the BIOVIA Biologics Solution powerfully supports the creative process and facilitates the movement of ideas from the brainstorming phase to product development. If your company is interested in learning more, please contact us today.
- “Psoriasis,” October 19, 2015, https://en.wikipedia.org/wiki/Psoriasis#History ↩
- “Causes and Triggers,” https://www.psoriasis.org/about-psoriasis/causes ↩
- “The role of T cells in psoriasis,” May 2003, http://www.ncbi.nlm.nih.gov/pubmed/12702062 ↩
- “New insights of T cells in the pathogenesis of psoriasis,” June 18, 2012, http://www.nature.com/cmi/journal/v9/n4/full/cmi201215a.html ↩
- “Moderate to Severe Psoriasis and psoriatic Arthritis: Biologic Drugs,” https://www.psoriasis.org/about-psoriasis/treatments/biologics ↩
- “Tcf3 and Tcf4 are essential for long-term homeostasis of skin epithelia,” December 14, 2009, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2792754/ ↩
- “The mesenchymal stem cell profile in psoriasis,” September 2011, http://www.ncbi.nlm.nih.gov/pubmed/21623755 ↩