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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. However, whether this pathway plays a role in other hair loss disorders remains unclear. The study aims at assessing STAT3 levels in male patients with androgenetic alopecia. The investigators 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.
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 androgen.
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. 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.
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.
Signal transducer and activator of transcription (STAT) proteins are transcription factorsprimarily phosphorylated and activated by JAKs.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. Growing evidence suggests that JAK inhibitors are efficacious in atopic dermatitis, alopecia areata, psoriasis and vitiligo.
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. However, whether this pathway plays a role in other hair loss disorders remains unclear. 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.
This 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:
The 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,.......)
Interventions :
Each subject will be subjected to:
Sample size (number of participants included)
Possible. Risk Bleeding, secondary infection, scarring.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Androgenetic alopecia patients | Two 1 mm scalp punch skin biopsy will be taken per patient |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Punch skin biopsy | Other | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Different in STAT3 | 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). | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Correlating STAT3 with severity | The relation of STAT3 levels to the severity of androgenetic alopecia (Hamilton-Norwood scale) | 6 months |
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Inclusion Criteria:
Exclusion Criteria:
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Specialized dermatology clinic at Cairo University
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| Name | Affiliation | Role |
|---|---|---|
| Akmal S Hassan, MD | Cairo University | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cairo University | Cairo | 12311 | Egypt |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28139263 | Background | Damsky W, King BA. JAK inhibitors in dermatology: The promise of a new drug class. J Am Acad Dermatol. 2017 Apr;76(4):736-744. doi: 10.1016/j.jaad.2016.12.005. Epub 2017 Jan 28. | |
| 14585162 | Background | Ellis JA, Sinclair R, Harrap SB. Androgenetic alopecia: pathogenesis and potential for therapy. Expert Rev Mol Med. 2002 Nov 19;4(22):1-11. doi: 10.1017/S1462399402005112. |
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| ID | Term |
|---|---|
| D000505 | Alopecia |
| ID | Term |
|---|---|
| D007039 | Hypotrichosis |
| D006201 | Hair Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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1mm punch skin biopsies will be taken to be analyzed by PCR
| 26601320 | Background | Harel S, Higgins CA, Cerise JE, Dai Z, Chen JC, Clynes R, Christiano AM. Pharmacologic inhibition of JAK-STAT signaling promotes hair growth. Sci Adv. 2015 Oct 23;1(9):e1500973. doi: 10.1126/sciadv.1500973. eCollection 2015 Oct. |
| 22134564 | Background | Magro CM, Rossi A, Poe J, Manhas-Bhutani S, Sadick N. The role of inflammation and immunity in the pathogenesis of androgenetic alopecia. J Drugs Dermatol. 2011 Dec;10(12):1404-11. |
| 25587654 | Background | O'Shea JJ, Schwartz DM, Villarino AV, Gadina M, McInnes IB, Laurence A. The JAK-STAT pathway: impact on human disease and therapeutic intervention. Annu Rev Med. 2015;66:311-28. doi: 10.1146/annurev-med-051113-024537. |
| 20584561 | Background | Paniagua RT, Fiorentino DF, Chung L, Robinson WH. Tyrosine kinases in inflammatory dermatologic disease. J Am Acad Dermatol. 2011 Aug;65(2):389-403. doi: 10.1016/j.jaad.2010.04.026. Epub 2010 Jun 26. |
| 26633291 | Background | Schwartz DM, Bonelli M, Gadina M, O'Shea JJ. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases. Nat Rev Rheumatol. 2016 Jan;12(1):25-36. doi: 10.1038/nrrheum.2015.167. Epub 2015 Dec 3. |
| 15020666 | Background | Rawlings JS, Rosler KM, Harrison DA. The JAK/STAT signaling pathway. J Cell Sci. 2004 Mar 15;117(Pt 8):1281-3. doi: 10.1242/jcs.00963. No abstract available. |
| 11511857 | Background | Whiting DA. Possible mechanisms of miniaturization during androgenetic alopecia or pattern hair loss. J Am Acad Dermatol. 2001 Sep;45(3 Suppl):S81-6. doi: 10.1067/mjd.2001.117428. |
| 25129481 | Background | Xing L, Dai Z, Jabbari A, Cerise JE, Higgins CA, Gong W, de Jong A, Harel S, DeStefano GM, Rothman L, Singh P, Petukhova L, Mackay-Wiggan J, Christiano AM, Clynes R. Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med. 2014 Sep;20(9):1043-9. doi: 10.1038/nm.3645. Epub 2014 Aug 17. |
| D020763 |
| Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |