Team:NYMU-Taipei/Description
WHAT IS ANDROGENETIC ALOPECIA?
Androgenetic alopecia (AGA), or commonly referred to hair loss in men and women. In men, this specific hair loss pattern (male-pattern baldness) leads to the formation of an “M” shaped hairline, and gradually proceeds to partial or complete baldness. Symptoms of AGA may start from a young age, and the risk increases with age. The prevalence of AGA in men above 50 years old is higher than 50%, dependent of countries and regions. The current understanding of the mechanism underlying AGA shows that AGA is highly related to dihydrotestosterone (DHT). DHT is an androgen hormone formed from the catalyzation of testosterone via 5ɑ-reductase. The androgen receptors in the dermal papilla (DP) cells will bind to DHT, and thereby upregulates the expression of dickkopf 1 (DKK-1). DKK-1 binds to low-density-lipoprotein-related protein 5/6 (LRP5/6) and Kremen protein, resulting in the inhibition of Wnt/ß-catenin pathway. The inhibition of Wnt/ß-catenin pathway inhibits the formation of hair follicles and also the growth of root sheath cells in hair follicles. This process eventually shortens the anagen phase of hair growth and causes miniaturization of the hair follicle, leading to hair loss.
CURRENT PROBLEMS
According to US Pharmacia Consumer Health Care’s estimations, men spend around $800 million on hair transplant and $225 million on baldness medical treatment per year, adding up to over $1 billion fighting AGA every year. Men have been investing $60 million on vitamin and nutritional supplements for regrowing their hair. In Taiwan, the rate of hair loss is 39% with the majority of hair loss occurring in young men (60%). Despite that, South Korea has a higher incidence of hair loss at a staggering 47%, their baldness tends to be older, with only 30% recognising hair loss between the age of 25 and 30. In the UK 40% of men have noticeable hair loss by age 35, 65% by age 60, and 80% by age 80. British men are the most worrisome about balding in Europe and 60% of hair loss sufferers would rather have more hair than money and friends. Usually, we lose our hair at the rate of 100 strands of hair per day, based on the average scalp containing 100 thousand hair follicles but 75% of British men believe hair loss cannot be prevented.
There are few methods to the hair loss treatments available such as Propecia and Finasteride, they contain the blocking effect of DHT on the hair follicles. These are popular and successful treatment in men suffering from male pattern baldness. Nevertheless, there are common side effects associated with those drugs such as breast enlargement, decreased libido, erectile dysfunction and ejaculation disorders. Moreover for the serious side effects included increased jeopardise of receiving undesirable prostate cancer and male breast cancer.
We have interviewed a doctor from Department of Dermatology, Dr.Chih-Chiang Chen, from Taipei Veterans General Hospital and he told us three points of current research on hair loss pattern in human. Firstly, there is no good mouse model for scientists for undergoing the experiment to find the remedies for the shrinking in the hair follicles. Secondly, it is difficult to examine which drugs are actually useful to grow hair back in the head. Lastly, a quick screening tool is needed for detecting the size of hair follicle so that this device can actually prove the reason why hair is in the stage of telogen or anagen.
WHAT ARE WE DOING?
Our team aims to provide a quick and easy platform to determine the effectiveness of hair loss product without animal or human testing. Since over-expression of DKK-1 is one of the main contributing factors that lead to AGA, the fast screening of effective products can be done by detecting the change in DKK-1 secretion levels after the products are added to the cells. If the expression of DKK-1 is down-regulated, the product can be a potential candidate for AGA treatment. Our project is divided into three parts, each using a different method to achieve the same goal.
The first part of the project uses an androgen responsive DP cell-line to evaluate the response of DP cells to different medicine. A luciferase producing gene along with DKK-1 promoter will be added into the cells via transient transfection, and the detection of DKK-1 protein amount can be determined by quantifying the amount of luciferase produced.
The second method is similar to the first one, except for using HEK 293 cells as our cell model. This is because DP cell-lines are relatively expensive and difficult to raise. If the result proves to accord with that of the first part, it could be a cheaper and more accessible in alternation that mimics the scenario in DP cells.
The third part of the project uses FRET technique to determine the amount of DKK-1 molecules. This method which serves our aim for convenience and affordability, since E.coli is used to produce two proteins that will emit fluorescence when bonded together. The amount of fluorescence emitted is proportional to the amount of DKK-1 secreted by the cell. Quantifying the amount of DKK-1 with this extracellular method allows users to conduct medicine selection via different kinds of cells. It also provides wider application potential, for it can be used in other researches related to DKK-1. Furthermore, the FRET method is both cheaper and more convenient than the traditional ELISA method, and provides a better choice for high-throughput screening (HTS) .