Androgenetic Alopecia and the JAK-STAT Pathway

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,.......)

• 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.

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.