Alopecia is a "fashionable" topic, even more so new solutions for baldness or experimental therapies in androgenetic alopecia; which are in the evaluation and development phase.
La androgenetic alopecia is a condition characterized by hair loss associated with progressive miniaturization of follicles. It is considered to be a condition caused by multiple factors, and the interaction between many genes y environmental factors extrinsic and intrinsic. Many studies have associated the gene of androgen receptor as the main responsible for this condition. Other associated genes are the 5-alpha-reductase, the gene of the aromatase and protein genes involved in cell signaling pathways like Wnt-Beta-catenin, among many others. Among the environmental factors involved are exposure to UV lightsmoke cigarette contamination, etc. When all these factors come together, triggers an inflammatory and oxidative stress process that contributes to hair loss.
Currently there are only two treatments approved by FDA of the United States for the treatment of androgenetic alopecia: The minoxidil and the finasteride. Neither solves the problem of alopecia, stop its progression to some extent but do not reverse the process must also be used indefinitely.
They also have a variable effectiveness and its use can cause Adverse effects. That is why they are developing novel therapies with the potential to be more effective for stop and reverse the alopecia process. Some of these therapies are in the experimental phase, so they are not yet readily available, but may become the first-line treatment in the future. Next we will talk about some of them.
This treatment is similar to PRP. Injections are applied directly to the scalp. The difference is that the PRP is obtained from the patient himself, while cytokines are derived from a commercial product with the name of HSC (hair-stimulating-complex). This product is produced in the laboratory using neonatal cells in culture grown in csimulated embryonic onditions. In these conditions, cells synthesize growth factors such as keratinocyte growth factor (KGF) and VEGF, which promote the proliferation of follicle stem cells. The clinical trials that have been carried out so far have shown promising results.
Analogues of Wnt.
There are many cellular signaling pathways involved in hair growth. One of them is protein Wnt-Beta-Catenin. This signaling pathway participates in the growth regulation of many cell types. Activation of the pathway Wnt stimulates that follicles enter the anagen phase of active growth. This protein also stimulates the dermal progenitor cells develop into a follicle. Results in new hair formation.
It has been shown that androgens inhibit activation of the pathway Wnt. Therefore, drugs that activate the Wnt signaling pathway could be used as a treatment for androgenetic alopecia. The valproic acid activates the path Wnt. A formulation topical de valproic acid has shown promising results in clinical trials. A protein-inducing molecule is also being developed Wnt (SM04554), which seems to be safe and well tolerated in the clinical trials that have been done. In them a significant clinical improvement has been found with the use of this experimental drug.
Treatment with stem cells or follicular cloning.
The use of stem cells in different medical fields like a regenerative therapy in cases of organ damage due to disease, trauma or aging. The ideal goal of this therapy is clone follicle stem cells and create a unlimited number of new follicles. What would be done is take a small area of scalp without baldness and isolate stem cells from follicles, which are responsible for hair regrowth. In a lab, those cells would multiply in large numbers and finally I know would implant in a bald area of the scalp. There They would generate new follicles immune to the baldness process.
Stem cell treatments are currently offered, however it is important to mention that these treatments are still in the development stages,therefore, they are not commercially available yet.
- In one study implanted bioengineered modified stem cells and it was shown that they were capable of producing functional follicles.
- In another study, culture grown follicular stem cellsObtained through a biopsy, they were injected into bald areas to stimulate hair growth.
- A Canadian company (RepliCel) is trying to create new folliclesby injection of autologous dermal cells. Clinical trials have shown increased total capillary density after 6 months of treatment.
- Stem cells derived from adipose tissue produce growth factors like VEGF. In clinical trials they have injected extracts from these cells directly on the scalp by microneedles. After 12 weeks treatment, an increase in the density and thickness of the hair is observed.
Theoretically, these treatments would reverse the baldness process in very advanced cases, especially when the donor area is insufficient to cover the areas that have been lost.
The tratment of gene therapy consists restore the lost expression of genes involved in the development of some condition or disease. For the therapy to be effective, the gene has to express yourself specifically where is required to express and a sufficient number of cells they must express it. Significant progress has been made in diseases caused by the single gene mutation. However, when more than one gene is involved, as in androgenetic alopecia, the solution becomes more complex.
The most efficient way to restore hair is reactivate miniaturized follicles, put them back into the active growth phase and restore the hair's normal cycle. The genes Wnt, SHH, FGF7 y STAR3 stimulate the onset of anagen phasewhile genes like FGF5 stimulate the onset of catagen phase. Therefore, these are genes that can be used to gene therapy.
Gene therapy methods
Once the gene to be used for therapy has been chosen, it must be effectively administered to the follicle by a method of type in vivo or ex vivo.
- El in vivo method it is simple and direct, however, for the expression to be maintained, it is required continuously manage it. They are usually used viral vectors or plasmids to insert the gene directly into the follicular cells. Administration can be topical using a mixture of liposomes which contain the Gene DNA (vector) or through a intradermal injection. Vectors can be used to maintain gene expression recombinant retrovirals.
- Find the model you want in ex vivo method that genes are introduced into cells in cell culture, later cells are implanted into white tissue. This method produces long-term gene expression, Because they can use stem cells and progenitor cells of the follicles that when they reproduce they will maintain the expression of the gene. Unfortunately, this method is more difficult to implement and the risks may be greater.
Because the primary goal of treatment is cycle modulation hair short-term gene expression could cause prolonged changesin the appearance of the hair.
This is how we look forward to observing the development of these experimental therapies in alopecia.