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Journal of Translational Medicine Apr 2024JAK-STAT signalling pathway inhibitors have emerged as promising therapeutic agents for the treatment of hair loss. Among different JAK isoforms, JAK3 has become an...
JAK-STAT signalling pathway inhibitors have emerged as promising therapeutic agents for the treatment of hair loss. Among different JAK isoforms, JAK3 has become an ideal target for drug discovery because it only regulates a narrow spectrum of γc cytokines. Here, we report the discovery of MJ04, a novel and highly selective 3-pyrimidinylazaindole based JAK3 inhibitor, as a potential hair growth promoter with an IC of 2.03 nM. During in vivo efficacy assays, topical application of MJ04 on DHT-challenged AGA and athymic nude mice resulted in early onset of hair regrowth. Furthermore, MJ04 significantly promoted the growth of human hair follicles under ex-vivo conditions. MJ04 exhibited a reasonably good pharmacokinetic profile and demonstrated a favourable safety profile under in vivo and in vitro conditions. Taken together, we report MJ04 as a highly potent and selective JAK3 inhibitor that exhibits overall properties suitable for topical drug development and advancement to human clinical trials.
Topics: Mice; Animals; Humans; Mice, Nude; Hair; Drug Development; Drug Discovery; Janus Kinase 3
PubMed: 38637842
DOI: 10.1186/s12967-024-05144-4 -
Skin Research and Technology : Official... Apr 2024Alopecia areata (AA) is often characterized by sudden onset of patchy hair loss. Topical corticosteroid injection is the most common treatment. This study...
OBJECTIVE
Alopecia areata (AA) is often characterized by sudden onset of patchy hair loss. Topical corticosteroid injection is the most common treatment. This study retrospectively observed the clinical efficacy of microneedle minoxidil combined with triamcinolone acetonide in the treatment of AA.
METHODS
A total of 230 patients with AA were selected. The experimental group (n = 120) received physician training and home microneedle treatment with minoxidil combined with triamcinolone acetonide once a week. Topical minoxidil and triamcinolone acetonide were used twice daily at other times. The control group (n = 110) was treated with minoxidil combined with triamcinolone acetonide, twice a day. Cure rate, response rate, SALT, dermatological Quality of Life Index (DLQI), visual analogue (VAS), and cost were assessed at weeks 4 and 12.
RESULTS
Treated group SALT score(Severity of Alopecia Tool) remarkable lower than control group after treated 4 and 12 weeks. After 12 weeks treatment, DLQI score of the treated group (1.8 ± 1.67) were significantly lower than those of the control group (2.45 ± 1.88) (p < 0.05). VAS score and adverse reaction between two group showed no significant different (p = 0.823, p = 0.484 respectively). The total cost was 53.93 ± 15.85 in the treatment group and 53.26 ± 11.51 in the control group. There was no significant difference between the two groups (p = 0.72). In the treated group, the complete response rate (CR: 78.33%) and total effective rate (CR+PR: 95%) were significantly higher than those in the control group (CR: 40.91% and CR+PR: 51.82%), with statistically significant differences (p < 0.001).
CONCLUSION
Microneedle introduction of minoxidil and triamcinolone acetonide in the treatment of AA is a safe, effective, economical, and convenient method, with few adverse reactions, and has a good application prospect.
Topics: Humans; Alopecia Areata; Triamcinolone Acetonide; Minoxidil; Retrospective Studies; Quality of Life; Alopecia; Treatment Outcome
PubMed: 38634160
DOI: 10.1111/srt.13713 -
Lasers in Medical Science Apr 2024Alopecia, also known as hair loss, is a highly prevalent condition affecting millions of men and women in the United States and worldwide, making it one of the most... (Review)
Review
Alopecia, also known as hair loss, is a highly prevalent condition affecting millions of men and women in the United States and worldwide, making it one of the most common complaints by patients presenting to a dermatologist. The symptomology on the presentation of alopecia can be highly variable, ranging from diffuse thinning of hair, discrete and localized patches completely absent of hair, or noticing significant shedding when brushing and showering. Although alopecia does not have a direct negative health impact on patients, it is nonetheless a debilitating disease as it can profoundly impact an individual's self-image and psychosocial well-being. There are multiple treatment options available to patients with alopecia, and they are typically tailored to the patient's needs and preferences. The most common of these is the Food and Drug Administration-approved drugs for alopecia, minoxidil, and finasteride. However, both of these are known to be partially efficacious for all patients, so clinicians often use different modalities in conjunction with them, in particular laser-based therapies. This review article will provide a comprehensive assessment of lasers and other light therapies that may be used to manage the two most common types of alopecia: androgenetic alopecia and alopecia areata.
Topics: Male; Humans; Female; Alopecia Areata; Hair; Lasers; Minoxidil
PubMed: 38630348
DOI: 10.1007/s10103-024-04054-7 -
Health Psychology Report 2024Alopecia is an autoimmune condition that results in hair loss, mainly from the scalp. There are three specific types of autoimmune alopecia: alopecia areata (AA; small...
BACKGROUND
Alopecia is an autoimmune condition that results in hair loss, mainly from the scalp. There are three specific types of autoimmune alopecia: alopecia areata (AA; small patches of hair loss), alopecia totalis (AT; total hair loss from the scalp) and alopecia universalis (AU; total hair loss from the scalp and body). Whilst research has explored the experiences of White women living with alopecia, there is a lack of research exploring the impact of alopecia on women in the Black community. The current study aimed to explore Black women's experience of living with autoimmune types of alopecia with a focus on the cultural importance of hair within the Black community and the impact of social support.
PARTICIPANTS AND PROCEDURE
Seven Black women (age range: 37-68 years; mean age: 51 years) were recruited purposively through alopecia support group organisations and social media to participate in a semi-structured interview; four participants were diagnosed with AA, two participants were diagnosed with AU, and one participant was diagnosed with AT. One-to-one interviews were conducted online, and interpretative phenomenological analysis was used to guide data collection and analysis.
RESULTS
Participants discussed the significance of hair specifically within the Black community and the complex relationship between psychological wellbeing, coping and seeking support.
CONCLUSIONS
This novel area, specific to Black women's psychological experience of alopecia, acknowledges the influence of cultural and ethnic differences. The findings suggest that proactive awareness from health professionals and social support groups are needed due to the nuances of Black women's alopecia experience to provide better support and to enhance the quality of life for Black women to manage their alopecia.
PubMed: 38628276
DOI: 10.5114/hpr/177730 -
Dermatology and Therapy Apr 2024Alopecia areata (AA) is an autoimmune skin disease presenting as nonscarring hair loss. Information on the epidemiology of AA, especially the occurrence of AA and its...
INTRODUCTION
Alopecia areata (AA) is an autoimmune skin disease presenting as nonscarring hair loss. Information on the epidemiology of AA, especially the occurrence of AA and its subtypes within the general population, is scarce. The study aimed to estimate the incidence rates and prevalence of hospital-treated AA and its subtypes in Denmark and to examine the demographic and clinical characteristics of patients with AA, including comorbidities and use of prescription medications.
METHODS
This was a cohort study based on data from administrative and health registers in Denmark in 1995-2016. The study included individuals who were (1) registered with a hospital inpatient or hospital-based outpatient clinic diagnosis of AA between 1995 and 2016 in the Danish National Patient Registry covering encounters at all Danish hospitals, (2) alive and resided in Denmark anytime between 1995 and 2016, (3) aged ≥ 12 years, and (4) resided uninterrupted in Denmark during the 12 months before the first AA diagnosis during the study period.
RESULTS
During the study period, 2778 individuals with an incident hospital-based diagnosis of AA were identified; 63.1% were female and 28.7% of the patients were aged ≥ 50 years. Over the study period, the overall incidence rate for any hospital-treated AA per 100,000 person-years was 2.62 (95% confidence interval [CI], 2.53-2.72), and the overall prevalence in 2016 was 71.7 (95% CI 69.4-74.1) per 100,000 persons. Both incidence rate and prevalence increased over time. Prevalence of most hospital-treated comorbidities or history of medication use was below 10% and was similar in the alopecia totalis (AT)/alopecia universalis (AU) and non-AT/AU subtypes of AA.
CONCLUSION
This cohort study reported incidence rates and prevalence over time and characteristics of individuals with hospital-treated AA in Denmark, which are in agreement with those previously reported in this population.
PubMed: 38625633
DOI: 10.1007/s13555-024-01145-9 -
Cureus Mar 2024Background and objective Alopecia areata (AA) is a reiterative and nonscarring type of hair loss that can affect any hairy area of the body, particularly the scalp. It...
Background and objective Alopecia areata (AA) is a reiterative and nonscarring type of hair loss that can affect any hairy area of the body, particularly the scalp. It manifests as patchy or confluent hair loss with variations in demographics and ethnicity. There are numerous treatment options available, including topical and systemic steroids, topical minoxidil, dithranol, tacrolimus, psoralen and ultraviolet therapy (PUVA), contact immunotherapy, and oral immunosuppressive drugs. However, no previous contrast for efficacy is present between the topical betamethasone versus topical minoxidil alone in our population. This study aims to compare the efficacy of topical betamethasone dipropionate versus topical minoxidil in patients with AA. Methodology A nonrandomized controlled study was conducted at the Department of Dermatology, Jinnah Hospital Lahore, incorporating the data of patients between July 26, 2016, and January 26, 2017, after obtaining institutional ethical approval. One hundred patients with alopecia, either on the scalp or any other hairy part, from both genders, aged between 18 and 50 years, were included in the study. Two groups were created, and patients were assigned to these groups based on the clinician's choice. Group A patients were administered betamethasone dipropionate (0.05%) lotion twice daily on affected areas for 12 weeks. Group B patients were administered minoxidil (5%) solution twice daily on affected areas for 12 weeks. A four-week follow-up plan was followed. A five-point scale score system was used for alopecia grading. After 12 weeks, the hair regrowth score (RGS) was used to compare the efficacy of treatment between the two groups. Results A total of 100 patients with grades S1 to S3 AA of less than three months duration were enrolled. Two groups were created, with 50 patients in each group. The mean age in Group A was 29.08 ± 6.51 years, while in Group B, it was 29.38 ± 6.62 years. In Group A, there were 76% males and 24% females, while in Group B, there were 74% males and 26% females. Comparison of efficacy of topical betamethasone dipropionate versus topical minoxidil in patients with AA demonstrated a greater efficacy of 74% (Grade 3 and Grade 4 responses) in Group A, while in Group B, only 42% of patients showed efficacy. A statistically significant difference was found, with a -value of 0.001. No serious side effects were noted. Conclusions Our study concluded that topical betamethasone dipropionate (0.05%) lotion has statistically significantly higher efficacy compared to topical minoxidil (5%) solution in patients with AA.
PubMed: 38623137
DOI: 10.7759/cureus.56282 -
Non-coding RNA Research Sep 2024DNA methylation is a crucial epigenetic alteration involved in diverse biological processes and diseases. Nevertheless, the precise role of DNA methylation in...
BACKGROUND
DNA methylation is a crucial epigenetic alteration involved in diverse biological processes and diseases. Nevertheless, the precise role of DNA methylation in chemotherapeutic drug-induced alopecia remains unclear. This study examined the role and novel processes of DNA methylation in regulating of chemotherapeutic drug-induced alopecia.
METHODS
A mouse model of cyclophosphamide (CTX)-induced alopecia was established. Hematoxylin-eosin staining and immunohistochemical staining for the Ki67 proportion and a mitochondrial membrane potential assay (JC-1) were performed to assess the structural integrity and proliferative efficiency of the hair follicle stem cells (HFSCs). Immunofluorescence staining and real-time fluorescence quantitative PCR (RT-qPCR) were performed to determine the expression levels of key HFSC markers, namely Lgr5, CD49f, Sox9, CD200, and FZD10. Differential DNA methylation levels between the normal and CTX-induced model groups were determined through simple methylation sequencing and analyzed using bioinformatics tools. The expression levels of miR-365-1, apoptosis markers, and DAP3 were detected through RT-qPCR and western blotting. In parallel, primary mouse HFSCs were extracted and used as a cell model, which was constructed using 4-hydroperoxycyclophosphamide. The luciferase reporter gene assay was conducted to confirm miR-365-1 binding to DAP3. To measure the expression of relevant indicators, superoxide dismutase (SOD) and malondialdehyde (MDA) kits were used. Methylation-specific PCR (MS-PCR) was performed to determine DNA methylation levels. The regulatory relationship within HFSCs was confirmed through plasmid overexpression of miR-365-1 and DAP3.
RESULT
In the alopecia areata model, a substantial number of apoptotic cells were observed within the hair follicles on the mouse backs. Immunofluorescence staining revealed that the expression of HFSC markers significantly reduced in the CTX group. Both RT-qPCR and western blotting demonstrated a noteworthy difference in DNA methyltransferase expression. Simple methylation sequencing unveiled that DNA methylation substantially increased within the dorsal skin of the CTX group. Subsequent screening identified miR-365-1 as the most differentially expressed miRNA. miR-365-1 was predicted and confirmed to bind to the target gene . In the CTX group, SOD and ATP expression markedly reduced, whereas MDA levels were significantly elevated. Cellular investigations revealed 4-HC-induced cell cycle arrest and decreased expression of HFSC markers. MS-PCR indicated hypermethylation modification of miR-365-1 in the 4-HC-induced HFSCs. The luciferase reporter gene experiment confirmed the binding of miR-365-1 to the DAP3 promoter region. miR-365-1 overexpression dramatically reduced apoptotic protein expression in the HFSCs. However, this effect was slightly reversed after DAP3 overexpression in lentivirus.
CONCLUSION
This study explored the occurrence of miR-365-1 DNA methylation in chemotherapeutic drug-induced alopecia. The results unveiled that miR-365-1 reduces cell apoptosis by targeting DAP3 in HFSCs, thereby revealing the role of DNA methylation of the miR-365-1 promoter in chemotherapeutic drug-induced alopecia.
PubMed: 38616861
DOI: 10.1016/j.ncrna.2024.03.001 -
Bioscience Trends Jun 2024Alopecia areata (AA) is an autoimmune disease characterized by damage to hair follicles and hair loss. Cell-free DNA (cfDNA) has recently received attention as a...
Alopecia areata (AA) is an autoimmune disease characterized by damage to hair follicles and hair loss. Cell-free DNA (cfDNA) has recently received attention as a biomarker of various disorders including inflammatory skin diseases. In this study, we aimed to investigate the clinical significance of cfDNA and the circulating DNAs of disease-associated cytokines in AA patients. Serum samples were obtained from 63 patients with AA and 32 healthy controls (HC). Using droplet digital polymerase chain reaction, circulating C-X-C motif chemokine ligand (CXCL) 9, CXCL10, CXCL11, C-X-C motif chemokine receptor 3, interferon (IFN)-γ, interleukin (IL) -7, IL-15, and Janus kinase (JAK) 2 were detectable in both HC and AA patients. Among the detectable DNAs, copies of circulating CXCL9, CXCL11, IL-15, IFN-γ, and JAK2 were significantly higher in AA patients than in HC. These results suggest that increased circulating DNA levels may reflect damage to hair follicles in AA patients.
Topics: Humans; Alopecia Areata; Cell-Free Nucleic Acids; Male; Female; Adult; Cytokines; Case-Control Studies; Biomarkers; Middle Aged; Young Adult; Janus Kinase 2; Chemokine CXCL9; Chemokine CXCL11; Interferon-gamma; Hair Follicle; Chemokine CXCL10; Adolescent; Interleukin-15
PubMed: 38616129
DOI: 10.5582/bst.2024.01084 -
International Journal of Women's... Jun 2024Janus kinase inhibitor (JAKi) therapy has revolutionized the treatment landscape for alopecia areata (AA); however, access may be limited by a lack of insurance coverage...
BACKGROUND
Janus kinase inhibitor (JAKi) therapy has revolutionized the treatment landscape for alopecia areata (AA); however, access may be limited by a lack of insurance coverage and high out-of-pocket costs.
OBJECTIVE
We aimed to evaluate real-world patient experiences regarding access to JAKi therapy.
METHODS
We conducted an online patient-centered survey using the National Alopecia Areata Foundation listserv.
RESULTS
In total 784 individuals initiated our survey, and 600 completed it in full (76.5%). While more non-White patients considered obtaining JAKi therapy, more White patients reported the use of this medication class. In total, 74.2% lacked insurance coverage or had partial coverage for JAKi, and 52% expressed dissatisfaction with available coverage. However, 52.9% reported delays in starting medication due to insurance approval processes, contributing to worsened AA and related stress. In total, 35% of patients did not try to obtain JAKi therapy due to concerns about costs, and 18.2% discontinued therapy due to financial barriers. Also, 19.8% of patients reported utilizing financial savings to pay for medication, and 55.2% reported using a copay assistance card. Further, 12.2% reported forgoing other necessities to pay for AA expenses.
LIMITATIONS
Our results are limited by the subjective nature of survey studies. The recency of FDA approval for JAKi therapy may also influence patients' perceptions of access to care.
CONCLUSION
Patients with AA face significant barriers when trying to obtain JAKi therapy, and existing racial inequities may be exacerbated by these barriers. Further advocacy work is needed to improve access to care.
PubMed: 38606145
DOI: 10.1097/JW9.0000000000000145 -
Dermatology and Therapy Apr 2024Alopecia areata (AA) affects approximately 2% of the general population and is associated with significant psychosocial morbidity and poor health-related quality of...
INTRODUCTION
Alopecia areata (AA) affects approximately 2% of the general population and is associated with significant psychosocial morbidity and poor health-related quality of life. Despite the high incidence of the disease the available clinical practice guidelines to help clinicians and improve patients' care are very poor and of a low methodological quality, as compared to other high-burden dermatoses. The aim of this survey is to capture the current clinical practice in AA management, as performed by dermatologists, in two Mediterranean countries to identify potential disparities and gaps in diagnosis and treatment.
METHODS
A 50-item questionnaire was created in the English language and then translated into Greek and Italian language and sent to the Greek and Italian dermatologists via email.
RESULTS
A total of 490 dermatologists from Italy and 234 from Greece participated in the survey. The diagnosis of AA is usually based on history and clinical examination, supported by trichoscopy. The rate of use of severity scores and scales to evaluate impact on quality of life by dermatologists was low. Treatment of patchy AA, in both adult and pediatric populations, is based on use of topical steroids as first-line treatment. Results on special site involvement (eyebrows, beard, and ophiasis), chronic cases, and the pediatric population highlight extreme heterogeneity in treatment approach.
CONCLUSIONS
Our results highlight that management of AA, in terms of diagnosis and treatment, is still challenging.
PubMed: 38598171
DOI: 10.1007/s13555-024-01141-z