Calcipotriene as psoriasis management

Calcipotrienevs

PsoriasisChong Boon HooiChristin Wong Ching YeeLaw Choon YikMishalni KanakarajahVincensa Nicko Widjaja

Psoriasis• Incurable - Chronic, noncontagious,

inflammatory disease which is genetically inherited (Meffert, 2016).

• High number of T cells - CD4+ & CD8+

• Th1 is activated by the presence of cytokines such as IL12, and IL15, and dendritic cells.

• Activation of Th1 - psoriasis phenotype

• Redness and hyperproliferation of keratinocytes (Krueger and Bowcock, 2005)

Calcipotriene

Year of Assessment

Assessment  Content Trial Phase

1991 Assessed for Long term safety and efficacy. 3

2005 Comparison of antipsoriatic efficacy, tolerability and acceptability of Calcipotriene ointment and Alphosyl HC cream in patients with plaque psoriasis affecting at least 100cm3 of the trunk and/ or limbs. Conclusion: The ointment is significantly more effective that Alphonsyl HC cream in the treatment of patients with plaque psoriasis with similar tolerability (Leo-pharma.com 2016)

4

First Marketed under the name of Dovonex in US

Development• Use of in vivo animal models,

immunodeficient mice (Petersen, 2006). • Hence, mice are unable to reject the human

skin grafts as they are genetically incapable of producing either T or B cells.

• Utilising this model, it has been shown that local proliferation of T cells in the pre-psoriatic skin is dependent on TNF-α production and this being essential for psoriatic lesion formation.

• Tests with established anti-psoriatic drugs such as Dovonex in the psoriasis SCID mouse model have generated result, which are similar to the results with clinical experiences (Petersen, 2016). Image showing psoriasis on mouse

model (E-id.org 2016)

Mode of Action• Calcipotriene works by

mimicking Vitamin D (Psoriasis.org 2016).

• Uptaken by VDR epithelial receptors.

• Induce TFs responsible for cell proliferation inhibitors (genes are not well understood).

• May be combined with topical corticosteroids to reduce inflammation rate (Banka 2016). (Banka 2016)

Analogues• Tacalcitol

– More potent than Calcipotriene– Not metabolized by the body– Retains ability to bind VDR (Ohta et al 1996)

• Maxacalcitol– Higher efficacy than Tacalcitol in

vitro, lower in vivo– Adverse effects eg. Skin burning

sensation, irritation (Trémezaygues and Reichrath 2011)

Other analogues• Paricalcitol• Eldecalcitol• Alfacalcidol• SMD-429

Related Drugs• Bz-423, a 1, 4-benzodiazepine,

chemically related to the anxiolytic diazepam, has also been patented for the treatment of psoriasis.

• Bz-423 has been shown to suppress keratinocyte proliferation in a murine model.

• Bz-423 also promotes cell death and is thought to target the F1F0-ATPase.

The chemical structures of Bz-423 (top) and diazepam (bottom) Wikipedia (2016).

VerdictCalcipotriene is a great drug discovery, as

it helps to treat various dermatological diseases particularly, Psoriasis. It is development process educates us in various areas, such as the development using the in vivo model despite Psoriasis being a disease that only affect humans. Hence, this discovery not only help in treating various diseases, it is also an advancement in the development technique.

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