Drug AS-101 as a candidate treatment for alopecia areata
AS-101 is an immunomodulatory drug [an agent that stops immune cell attack]
as well as a hair growth promoter and is used in patients who experience alopecia
after chemotherapy. The drug was tested for its immuno suppressive effects on
the inflammatory activity of blood cells from children in the age group of 3-15
who have patchy alopecia areata.
Cytokines are proteins secreted by the inflammatory and regulatory
cells of the immune system and are seen to promote or regulate
immune responses in alopecia areata. Hence a study of cytokine
profile and effects due to exposure to AS-101 was carried out.
The patients who donated blood comprised of 10 members [5 boys
and 5 girls] with alopecia areata showing 20% hair loss, with
no previous treatment for the condition, but otherwise healthy,
along with 10 healthy age matched controls.
The sequence of the study is as follows:-
1. Using Ficoll-paque density gradient medium [a medium used for
isolating lymphocytes from human blood], peripheral mononuclear
white blood cells were isolated from blood samples obtained
from all 20 children.
2. Peripheral blood mononuclear cells were cultured in a nutrient
solution called RPMI-1640 medium at 37 degrees centigrade and
a 5% carbon dioxide atmosphere. RPMI-1640, or Roswell Park Memorial
Institute medium, is used commonly for growing human lymphoid
cells. It has high phosphate content and is specially formulated
to be used in a 5% carbon dioxide atmosphere.
3. The above mentioned cell cultures were divided into 4 sets.
The first set was the unstimulated version as described above.
The second set was stimulated with 10 microgram/mL phytohemaglutinin.
This is a chemical that stimulates white blood cells into making
an inflammatory response. The third set comprised of unstimulated
cells with AS-101 while the fourth set had 0.5 microgram/mL AS-101
along with the phytohemaglutinin.
4. After 48 h of incubation, the supernatants (the fluids) from
each set of cultures were frozen.
5. Using ELISA [Enzyme Linked Immunosorbent Assay], Cytokines
Interferon gamma, Interleukin 10 [IL-10], IL-6, IL-5 and the IL-2
receptor were estimated quantitatively.
6. All the results were statistically analyzed using the student
The findings of this study were-
1. In the unstimulated set without AS-101, the levels of IL-2R
and IL-6 were higher in patients with patchy alopecia areata in
comparison with their controls.
2. On stimulation with phytohemaglutinin, there was a four fold
increase of IL-5 in alopecia areata patients.
3. Treatment with AS-101 resulted in significant reduction in
the production of Interferon gamma, IL-10, IL-2R and IL-5. This
result is of importance in conducting further studies on AS-101
as a potential drug in treating patchy alopecia areata.
Apart from these findings, some of the results were consistent
with the findings of previous assessments.
1. IL-2R had higher solubility in peripheral blood mononuclear
cells of patchy alopecia areata patients and this was consistent
with the report of Valesecchi et al. in 1992.
2. Higher levels of IL-2R had been reported by Wüthrich
et al. in 1990 in patients with atopic dermatitis.
3. Increase in the levels of Interferon gamma and IL-10 was consistent
with the findings of Zoller et al. reported in 2004.
AS-101 behaves as a stimulant or suppressant depending on the
levels of cytokines in the cells. It has been reported to interfere
with IL-10 mRNA transcription thereby normalizing its physiological
levels simultaneously increasing IL-1 and Tumor necrosis factor
(TNF) alpha. The current finding of AS-101 controlling cytokines
in patchy alopecia areata patients suggests it might work as a
treatment for alopecia areata. The study authors claim further
studies are warranted.
Drug AS-101 as a candidate treatment for alopecia areata references
Shohat M, Mimouni D, Ben-Amitai
D, Sredni B, Sredni D, Shohat B, David M.
In vitro cytokine profile in childhood alopecia areata and the immunomodulatory
effects of AS-101.
Clin Exp Dermatol. 2005 Jul;30(4):432-4.