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Comparative activity of dimethyl fumarate derivative IDMF in three models relevant to multiple sclerosis and
Yulin He1, Guiyi Gong1, Geovani Quijas2
1Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hung Hom, China.
Abstract:
Dimethyl fumarate (DMF) is an anti-inflammatory and immunoregulatory medication used to treat multiple sclerosis (MS) and psoriasis. Its skin sensitization property precludes its topical use, which is unfortunate for the treatment of psoriasis. Isosorbide di-(methyl fumarate) (IDMF), a novel derivative of DMF, was synthesized to circumvent this adverse reaction and unlock the potential of topical delivery, which could be useful for treating psoriasis in the subpopulation of psoriatic MS patients, as well as in the general population. Here, we compared its therapeutic potential of this non-sensitizing derivative with DMF and its therapeutic version Diroximel in three skin- and neuroinflammation models: the lck-GFP zebrafish, activated BV-2 murine microglia and human T-lymphocyte Jurkat cell line. The results provide a comparative evaluation of the bioactivity of these three related chemical entities in models relevant to skin and neuroinflammation and expose several therapeutic advantages unique to IDMF.
Insights
Isosorbide di-(methyl fumarate) (IDMF), a new dimethyl fumarate (DMF) derivative, shows promise for topical skin and neuroinflammation treatment without causing skin sensitization. IDMF offers unique therapeutic advantages over DMF and Diroximel.
Area of Science:
- Pharmacology
- Immunology
- Dermatology
Background:
- Dimethyl fumarate (DMF) is an effective anti-inflammatory and immunoregulatory drug for multiple sclerosis (MS) and psoriasis.
- DMF's utility in topical psoriasis treatment is limited by its skin sensitization potential.
- Isosorbide di-(methyl fumarate) (IDMF) was developed as a non-sensitizing derivative of DMF for enhanced topical delivery.
Purpose of the Study:
- To compare the therapeutic potential of the novel non-sensitizing derivative, IDMF, against DMF and Diroximel.
- To evaluate IDMF's efficacy in preclinical models of skin and neuroinflammation.
- To identify unique therapeutic advantages of IDMF for inflammatory skin and neurological conditions.
Main Methods:
- Comparative bioactivity assessment of IDMF, DMF, and Diroximel.
- Utilized three distinct models: lck-GFP zebrafish (skin inflammation), activated BV-2 murine microglia (neuroinflammation), and human T-lymphocyte Jurkat cell line.
- Assessed anti-inflammatory and immunomodulatory effects in vitro and in vivo.
Main Results:
- IDMF demonstrated significant therapeutic potential in models relevant to skin and neuroinflammation.
- The novel derivative IDMF exhibited a favorable profile compared to DMF and Diroximel.
- IDMF possesses unique therapeutic advantages, particularly for topical applications, due to its non-sensitizing properties.
Conclusions:
- IDMF represents a promising non-sensitizing alternative to DMF for topical treatment of inflammatory conditions like psoriasis.
- The findings support IDMF's potential for treating psoriatic MS patients and the general population.
- IDMF's unique properties open new avenues for topical anti-inflammatory and immunomodulatory therapies.
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