Study to Determine Effect of Gentle Wounding to Stimulate Hair Follicle Neogenesis

Central centrifugal cicatricial alopecia (CCCA) is a scarring, inflammatory alopecia seen
more commonly in women of African descent. The distinct pathophysiology of CCCA is poorly
understood, but it is known to involve inflammation directed at the upper part of the hair
follicle where the stem cells and sebaceous gland are located. If the stem cells and
sebaceous gland are destroyed, there is no possibility for regeneration of the hair follicle,
and permanent hair loss results. This form of scarring alopecia occurs mainly on the vertex
of the scalp, and spreads peripherally, and can lead to baldness. In our dermatology clinics,
our investigators see 5-10 patients per week for evaluation and treatment of CCCA.

Currently, treatment is focused on decreasing inflammation and halting the progression of
disease. This typically consists of topical and intralesional corticosteroid therapy and
anti-inflammatory antibiotics. Hair transplantation is the only treatment option for patients
with end-stage CCCA, and has been performed in a small number of patients but the results
have been disappointing with low graft survival rates and slow regrowth of the transplanted
hair. In addition, hair transplantation of the curved hair follicles found in patients of
African descent is difficult and requires specific expertise.

A study by Ito et al showed de novo hair follicle formation after wounding in genetically
normal adult mice. The regenerated hair follicles were fully functional, in that they
established a stem cell population, expressed known molecular markers of follicle
differentiation, and produced a hair shaft that progressed normally through all stages of the
hair follicle cycle. It is hypothesized that the regenerated hair follicles likely arise when
epithelial cells in the wound assume a hair follicle stem cell phenotype, possibly under the
influence of Wnt signaling.

The CO2 laser has been used extensively in dermatological surgery over the past 30 years and
is now recognized as the gold standard for soft tissue vaporization. CO2 laser beam heats and
vaporizes the skin tissue, instantly removing the superficial layers of the skin. Each
fractional micro-spot creates a thermal zone. Intact cells around the treated area help
during the healing process which in turn, induces cell regeneration. This likely occurs
through dsRNA released during wounding. The investigators have recently found that retinoids,
such as the tretinoin (retin-A) used in acne, can synergize with dsRNA and promote extra Wnt
signaling.

The investigators therefore hypothesize that wounding of the area of scarring alopecia in
CCCA, using a fractionated CO2 laser in combination with retinoid acid, will induce hair
follicle regeneration.

Inclusion criteria

Subjects who meet the following inclusion criteria will be included in the study:

- Male or female older than 18 at the screening visit;

- The subject is healthy, as determined by the investigator based on a medical
evaluation including medical history;

- The subject has clinical diagnosis of CCCA;

- The subject's CCCA is of grades 2, 3 or 4, as assessed at the time of the screening
visit.

- The subject is willing and able to comply with the requirements of the protocol. In
particular, subject must adhere to the visits schedule, concomitant therapy and hair
processing prohibitions, subject instructions, and biopsy procedures;

- The subject is willing to comply with the month long washout period if deemed
necessary;

- The subject has understood and signed an Informed Consent Form approved by the
Institutional Review Board (IRB) prior to any investigational procedure Exclusion
criteria

Any subject who is meeting one or more of the following exclusion criteria at the screening
visit and/or at the baseline visit will not be included in this study:

- The subject has an underlying known disease, a surgical or medical condition that in
the opinion of the investigator might put the subject at risk

- The subject presents with any disease known or described to potentially interfere with
a normal wound healing process

- The subject is pregnant or breastfeeding at the time of enrollment or is planning to
become pregnant at any point during the study period (by self report)

- The subject has a past history of coagulation trouble

- The subject has a past history of abnormal healing (hypertrophic scars/keloids within
the past 10 years)

- The subject has an underlying dermatological disease that in the opinion of the
investigator could interfere with the study evaluations

- The subject has scars, sunburn, either damaged or broken (cuts or abrasions) skin or
other blemishes, or tattoos on the scalp in the treatment area

- The subject is unwilling or unable to refrain from specific types of chemical hair
styling and processing, including perms, straighteners, relaxers, dyes, weaves

- The subject has a known allergy or sensitivity to any local anesthetic drug (e.g.
lidocaine) or a local antiseptic planned to be used for the laser and/or biopsy
procedures

- The subject is in an exclusion period from a previous study or is participating in
another clinical trial

- The subject is an adult under guardianship or is hospitalized in a public or private
institution, or is deprived of freedom

- The subject is unable to communicate or cooperate with the Investigator due to
language problems, poor mental development, or impaired cerebral function