Topical SCD-153, a 4-methyl itaconate prodrug, for the treatment of alopecia areata
Jerry TsaiSadakatali S. GoriJesse AltSandhya P. TiwariJitesh IyerRashmi TalwarDenish HinsuKailash AhirwarSwayam MohantyChintan KhuntBrijesh SutariyaKaushal J JaniVenkatesha VenkatasubbaiahAshok R. PatelJasmin MeghaparaKaushal JoshiRajanikanta SahuVijay RanaPrashant B. NigadeRavi S. TalluriKadiyala V S N MurtyKiritkumar JoshiVikram RamanathanAng LiNasif IslamIvan ŠnajdrPavel MajerRana RaisBarbara S. SlusherLuis A. Garza
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Abstract:
Alopecia areata is a chronic hair loss disorder that involves autoimmune disruption of hair follicles by CD8+ T cells. Most patients present with patchy hair loss on the scalp that improves spontaneously or with topical and intralesional steroids, topical minoxidil, or topical immunotherapy. However, recurrence of hair loss is common, and patients with extensive disease may require treatment with oral corticosteroids or oral Janus kinase (JAK) inhibitors, both of which may cause systemic toxicities with long-term use. Itaconate is an endogenous molecule synthesized in macrophages that exerts anti-inflammatory effects. To investigate the use of itaconate derivatives for treating alopecia areata, we designed a prodrug of 4-methyl itaconate (4-MI), termed SCD-153, with increased lipophilicity compared to 4-MI (CLogP 1.159 vs. 0.1442) to enhance skin and cell penetration. Topical SCD-153 formed 4-MI upon penetrating the stratum corneum in C57BL/6 mice and showed low systemic absorption. When added to human epidermal keratinocytes stimulated with polyinosinic-polycytidylic acid (poly I:C) or interferon (IFN)γ, SCD-153 significantly attenuated poly I:C-induced interleukin (IL)-6, Toll-like receptor 3, IL-1β, and IFNβ expression, as well as IFNγ-induced IL-6 expression. Topical application of SCD-153 to C57BL/6 mice in the resting (telogen) phase of the hair cycle induced significant hair growth that was statistically superior to vehicle (dimethyl sulfoxide), the less cell-permeable itaconate analogues 4-MI and dimethyl itaconate, and the JAK inhibitor tofacitinib. Our results suggest that SCD-153 is a promising topical candidate for treating alopecia areata.Raymond said in 1892 that "nothing is easier to cure than alopecia areata; one only has to refer to the recent enthusiastic publications...."1Several current reports of the successful treatment of alopecia areata with dinitrochlorobenzene2-4have raised the question as to whether treatment effects are directly related to the allergic reaction or to other phenomena associated with an allergic contact dermatitis. We therefore attempted to induce hair growth in patients with alopecia areata by producing an inflammatory nonallergic dermatitis. Anthralin (dithranol) in 0.2% to 0.8% concentrations is known to induce irritant dermatitis without serious side effects.5This report concerns 32 patients with alopecia areata who were advised to apply anthralin as often as necessary in order to induce a visible but tolerable dermatitis.
Patients and Methods
Thirty-two patients ranging in age from 12 to 71 years were treated; 27 were men and five were women. Twenty-four patientsDithranol
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Raymond said in 1892 that "nothing is easier to cure than alopecia areata; one only has to refer to the recent enthusiastic publications...."1Several current reports of the successful treatment of alopecia areata with dinitrochlorobenzene2-4have raised the question as to whether treatment effects are directly related to the allergic reaction or to other phenomena associated with an allergic contact dermatitis. We therefore attempted to induce hair growth in patients with alopecia areata by producing an inflammatory nonallergic dermatitis. Anthralin (dithranol) in 0.2% to 0.8% concentrations is known to induce irritant dermatitis without serious side effects.5This report concerns 32 patients with alopecia areata who were advised to apply anthralin as often as necessary in order to induce a visible but tolerable dermatitis.
Patients and Methods
Thirty-two patients ranging in age from 12 to 71 years were treated; 27 were men and five were women. Twenty-four patientsDithranol
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<p class="abstract">Twenty nail dystrophy mainly describes roughness of nail which can be idiopathic or it could be associated with various other dermatological conditions like psoriasis, alopecia areata and eczema. Here we report a case of twenty nail dystrophy with alopecia areata of scalp in a 6-year-old child.</p>
Dystrophy
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Alopecia areata (AA) is suddenly occurring, non-scarring hair loss disease. There are many theories, and many
implied factors, but the true pathogenesis of AA is still not clear. In this review we discuss therapy of AA, topical,
systemic and biologics.
Few cases are presented with dermoscopic (trichoscopic) view of the scalp, and use of trichoscopy in prognosis of AA.
This is a completely benign condition, but devastating for a patient and requires multidiscipline.
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Бұл зерттеужұмысындaКaно моделітурaлы жәнеоғaн қaтыстытолықмәліметберілгенжәнеуниверситетстуденттерінебaғыттaлғaн қолдaнбaлы (кейстік)зерттеужүргізілген.АхметЯссaуи университетініңстуденттеріүшін Кaно моделіқолдaнылғaн, олaрдың жоғaры білімберусaпaсынa қоятынмaңыздытaлaптaры, яғнисaпaлық қaжеттіліктері,олaрдың мaңыздылығытурaлы жәнесaпaлық қaжеттіліктерінеқaтыстыөз университетінқaлaй бaғaлaйтындығытурaлы сұрaқтaр қойылғaн. Осы зерттеудіңмaқсaты АхметЯсaуи университетіндетуризмменеджментіжәнеқaржы бaкaлaвриaт бaғдaрлaмaлaрыныңсaпaсынa қaтыстыстуденттердіңқaжеттіліктерінaнықтaу, студенттердіңқaнaғaттaну, қaнaғaттaнбaу дәрежелерінбелгілеу,білімберусaпaсын aнықтaу мен жетілдіружолдaрын тaлдaу болыптaбылaды. Осы мaқсaтқaжетуүшін, ең aлдыменКaно сaуaлнaмaсы түзіліп,116 студенткеқолдaнылдыжәнебілімберугежәнеоның сaпaсынa қaтыстыстуденттердіңтaлaптaры мен қaжеттіліктерітоптықжұмыстaрaрқылыaнықтaлды. Екіншіден,бұл aнықтaлғaн тaлaптaр мен қaжеттіліктерКaно бaғaлaу кестесіменжіктелді.Осылaйшa, сaпa тaлaптaры төрт сaнaтқa бөлінді:болуытиіс, бір өлшемді,тaртымдыжәнебейтaрaп.Соңындa,қaнaғaттaну мен қaнaғaттaнбaудың мәндеріесептелдіжәнестуденттердіңқaнaғaттaну мен қaнaғaттaнбaу деңгейлерінжоғaрылaту мен төмендетудеосытaлaптaр мен қaжеттіліктердіңрөліaйқын aнықтaлды.Түйінсөздер:сaпa, сaпaлық қaжеттіліктер,білімберусaпaсы, Кaно моделі.
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