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Androgenetic Alopecia and the JAK-STAT Pathway

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信息的提供 (责任方):
Aya AlOrbani,Cairo University
October 1, 2018
October 3, 2018
October 3, 2018
October 15, 2018
February 1, 2019   (主要结果测量的最终数据收集日期)
Different in STAT3[ Time Frame: 6 months ]
STAT3 levels in androgen-dependant areas compared to non-involved areas from occipital scalp(in an attempt to assess the possible role of the JAK-STAT pathway in androgenetic alopecia).

与当前相同
  • Correlating STAT3 with severity[ Time Frame: 6 months ]
    The relation of STAT3 levels to the severity of androgenetic alopecia (Hamilton-Norwood scale)
 
Androgenetic Alopecia and the JAK-STAT Pathway
Assessment of the Role of the JAK-STAT Pathway in the Pathogenesis of Male Androgenetic Alopecia

It is a well known fact that the JAK-STAT pathway plays a pivotal role in the pathogenesis of alopecia areata. Both phosphorylated STAT 1 and 3 have been found to be upregulated in the disease (Xing et al., 2014). However, whether this pathway plays a role in other hair loss disorders remains unclear.(Sivan et al., 2015). Our study aims at assessing STAT3 levels in male patients with androgenetic alopecia. We hypothesize that STAT3 levels will be elevated (due to a previous study proving that JAK-STAT pathway is involved in non-immune mediated hair loss in mice (Sivan et al., 2015)). .

Background and rationale Androgenetic alopecia occurs in men and women,and is characterised by the loss of hair from the scalp in a defined pattern. Determining factors appear to be genetic predisposition coupled with the presence of sufficient circulating androgens(Ellis etal., 2002). The transformation of testosterone into dihydrotestosterone(DHT) by type 2 5-alpha reductase, which causes hair miniaturization,is universally accepted as the main player in the disease's pathogenesis (Whiting, 2001) Nonetheless,how DHT causes hair thinning is not well understood. New studies revealed that a lymphocytic microfolliculitis targeting the bulge epithelium along with deposits of epithelial basement membrane zone immunoreactants are frequent findings in androgenetic alopecia and could point toward an immunologically driven trigger (Magro et al., 2011). Tyrosine kinases (TKs) are enzymes involved in intracellular signaling that catalyze the phosphorylation of tyrosine residues on protein substrates. They are key components of signaling pathways that drive any array of cellular responses including proliferation, differentiation, migration and survival. Janus kinases (JAKs) are specific TKs (Paniagua et al., 2011). Signal transducer and activator of transcription (STAT) proteins are transcription factorsprimarily phosphorylated and activated by JAKs(Rawlings et al., 2004).The JAK-STAT pathway is utilized by cytokines including interleukins (ILs), interferons (IFNs), and other molecules to transmit signals from the cell membrane to the nucleus(Schwartzetal.,2016; O'Shea et al., 2015).Growing evidence suggests that JAK inhibitors are efficacious in atopic dermatitis, alopecia areata, psoriasis and vitiligo(Damsky and King, 2017). It is a well known fact that the JAK-STAT pathway plays a pivotal role in the pathogenesis of alopecia areata. Both phosphorylated STAT 1 and 3 have been found to be upregulated in the disease (Xing et al., 2014). However, whether this pathway plays a role in other hair loss disorders remains unclear.(Sivan et al., 2015). A study showedthat topical treatment of mouse and human skin with small molecule inhibitors of the JAK-STATpathway resulted in rapid onset of anagen and subsequent hair growth. It was shown that JAK inhibition regulates the activation of key hair follicle populations such as the hair germ. These findings indicate that the JAK-STAT pathway may be involved, not only in immune-mediated hair loss (alopecia areata), but also in the normal hair cycle(Sivan et al., 2015). Our current study aims at assessing STAT3 levels in patients with androgenetic alopecia, in an attempt to detect a possible role of the JAK-STAT pathway in the pathogenesis of the disease. Objective: Our objective is to compare tissue levels of STAT3 in androgen-dependant areas in male androgenetic alopecia patients with their level in non-involved, non-androgen dependant areas (occipital scalp) in the same subjects. Population of study & disease condition (e.g women with hepatitis, ............) Males with androgenetic alopecia Background and demographic characteristics( e.g age,.......) - Age above 18 years. - Males Interventions : Each subject will be subjected to: - Informed consent. - Detailed history and clinical evaluation to determine severity of disease. - Punch biopsies (1mm) of affected area of scalp (androgen dependent area) from 25 patients with androgenetic alopecia. - Punch biopsies(1mm) of normal area of scalp from occipital scalp (non-androgen dependent area) from the same 25 patients - Quantification of STAT3 by polymerase chain reaction (PCR). Sample size (number of participants included) - 25 participants (That will serve as both patients and controls) - Sample size calculation was done using G ⃰ Power 3.1.9.2. Possible. Risk Bleeding, secondary infection, scarring.
Observational
分配:
干预模型:
干预模型描述:
盲法: Observational
盲法描述:
主要目的:
  • Other: Punch skin biopsy
    One 1 mm punch biopsy will be taken from the patients from balding scalp. Another 1 mm punch biopsy will be taken from an area of occipital non-balding scalp of the same individual. Local anesthesia will be injected around the biopsy site beforehand.
  • : Androgenetic alopecia patients
    Two 1 mm scalp punch skin biopsy will be taken per patient
 
Not yet recruiting
25
与当前相同
April 1, 2019
February 1, 2019   (主要结果测量的最终数据收集日期)
Inclusion Criteria: - Males with androgenetic alopecia not receiving topical treatment nor systemic treatment for hair loss for at least 6 month prior to the study Exclusion Criteria: - Patients with localized or generalized hair loss due to causes other than androgenetic alopecia.
参与研究的性别: Male
最小年龄:18 Years ,最大年龄:N/A  
没有
Egypt
 
No
研究美国FDA监管的药品: No
研究涉及美国FDA监管的设备产品: No
计划分享 IPD: No
Aya AlOrbani,Cairo University
Cairo University
Study Director: Akmal S Hassan, MD Cairo University
Cairo University
October 2018

ICMJE     国际医学期刊编辑委员会和 世界卫生组织 ICTRP 要求的元素
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