Dr George Cotsarelis and colleagues at the University of Pennsylvania in Philadelphia have successfully incorporated genes into normal growing hair follicles. They recently reported that “successful transfection of human hair follicles using topical liposomes is optimal at the onset of anagen”. This study was first presented at the Society for Investigative Dermatology annual conference in Chicago, May 1999.

Previously it was shown that topical liposomes could be used to transfer DNA to mouse hair follicles, but this is the first time that DNA has been successfully transferred to human hair follicles. Liposomes are very small, submicroscopic globules of oil. The liposomes are able to penetrate through skin very easily and they can act as carriers to take drugs, proteins, or even DNA into the skin.

Hair follicles include very active, rapidly dividing cells. These cells are continuously replicating their own DNA for inclusion in new cells. This means that hair follicle cells are very receptive to incorporation of new DNA. Potentially it should be quite easy to transfer a gene through the skin to hair follicles using liposomes. The liposomes penetrate the skin and then fuse with the walls of cells and release their DNA contents into the cells. The DNA is then included in new DNA made for new hair follicle cells. Dr Cotsarelis took advantage of this phenomenon and transferred a beta galactosidase reporter plasmid into human hair follicles. This plasmid contains the DNA code for a gene that makes a blue pigment.

Although this gene has no use in treating hair loss, Dr Cotsarelis and friends say the technique could be turned to growing hair someday. Dr. George Cotsarelis, director of the Hair and Scalp Clinic at the University, said in a statement. “These early results in our ongoing research suggest that certain types of hair loss might be suitable for gene therapy,” The idea behind this kind of gene therapy is to use genetic material to replace a faulty gene, or to boost the efforts of genes normally active in hair follicles.

The research team found that they incorporated DNA most successfully into hair follicles when the follicles were in the very early stages of anagen growth. The research team believe this technique could be used in such diseases as alopecia areata where many hair follicles are in an early dystrophic anagen stage of growth. It could also be used in androgenetic alopecia where many hair follicles are in telogen. These inactive telogen hair follicles could be induced into an early anagen and then have a gene therapy applied to promote full terminal hair regrowth.

The research shows that gene therapy could be very effective in treating many forms of hair loss where genes are involved. The gene application using liposomes could be used to replace faulty genes that cause hereditary hair loss. The treatment techniques may also be used to reactivate switched off, normal, healthy genes and encourage hair growth after hair loss caused by environmental factors as can occur in telogen effluvium. The technique could even be used to block the activity of unwanted genes such as those involved in 5 alpha reductase activity. 5 alpha reductase is the enzyme that converts testosterone to dihydrotestosterone. However, the biggest challenge is to identify suitable genes that can be used as an effective treatment for hair loss.

Unless the hair follicle stem cells are successfully transfected with the desired genes, the treatment will have to be regularly re-applied to have a continued effect. Cells die off rapidly in hair follicles. Most are incorporated into the growing hair fiber. This means that the transferred gene can be lost. In the research presented Dr Cotsarelis and company, they found the gene they transfected disappeared from hair follicles after a month or two. It may prove to be very difficult to transfect the stem cells (the true source of all the cells made in hair follicles) and make gene therapy a single application and permanent cure for hair loss diseases.