# Ceramide Analog Control of Cutaneous Inflammation

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2022 · —

## Abstract

Common skin disorders with impaired barrier function represent a large and unmet need,
especially among both the very young and increasing elderly population. These disorders include
atopic dermatitis (7.3% of US adults), psoriasis (2-3% of US population), venous ulcers, stasis
dermatitis and actinic keratosis. Barrier restoration with emollients is commonly used for many of
these disorders, but is only partially effective. The fact that transepidermal water loss can be repaired
without curing the inflammation suggests that specific biochemical abnormalities are not being
addressed by simple emollients. In the cases of severe inflammatory disorders, such as atopic
dermatitis and psoriasis, many biologics, targeting TNFα, IL-12, IL-17, IL-1β, and IL-4 have shown
benefit, but these therapies are usually reserved for the 10% of most severe cases due to side effects
and expense. The mainstay of less severe inflammatory skin disorders remains topical steroids, as it
has been for the last 40 years. Other topicals, such as retinoids, vitamin D, and topical
immunosuppressants have had less impact due to lesser efficacy and greater expense. Our central
hypothesis is that solenopsin derivatives, which have ceramide-like properties, can alleviate
inflammation, even in the face of infection. We test this hypothesis with novel ceramide analogs
based on the ant venom alkaloid solenopsin, which are not metabolized into pro-inflammatory
sphingosine-1 phosphate.
 It may be counterintuitive that a single signaling pathway could be inhibited to alleviate widely
different disorders including psoriasis and atopic dermatitis caused by inflammation and bacterial
colonization/infection. This speaks to the innovation of this protocol. Our preliminary data have
demonstrated that topical solenopsin derivatives have efficacy in well-established preclinical models of
atopic dermatitis (manuscript in preparation) and psoriasis 5. Moreover, these studies have
independently identified interleukin-12 (IL-12) as elevated in response to topical solenopsin analogs.
Given that IL-12 has also been implicated in infectious disease as well, it is therefore feasible that a
single molecule could be used in the treatment of both inflammatory and infectious diseases of the skin.
In addition, the burden of inflammatory and infectious skin disorders runs into tens of billions of dollars
annually with some treatment of inflammatory disorders predisposing to infection (corticosteroids) and
some anti-infectives having pro-inflammatory effects. Finally, a barrier restoration; IL-12 link could
provide a common final pathway for the resolution of inflammatory and infectious skin conditions. Our
discovery of IL-12 as a target of solenopsin analogs could be useful as novel adjuvants for vaccine
development as well.

## Key facts

- **NIH application ID:** 10368633
- **Project number:** 1I01BX005623-01A1
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** JACK L ARBISER
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2022-04-01 → 2022-04-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10368633

## Citation

> US National Institutes of Health, RePORTER application 10368633, Ceramide Analog Control of Cutaneous Inflammation (1I01BX005623-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10368633. Licensed CC0.

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