drug AS-101 as a candidate treatment for alopecia areata
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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 t-test.

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. PMID: 15953089
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