In last week's article, we discussed the challenges we face in trying to cure pattern hair loss. In this article, we'll explore a number of tools available as we seek to surmount this disease, one of the most common affecting humanity.
Today, modern molecular medicine encompasses the utilization of molecular biological techniques in the analysis of genes and gene dysfunction, each contributing to the onset and progression of disease. The study of genes and their healthy function in an unaffected individual has been rendered possible by the development of recombinant DNA and a related technique called cloning.
The basis of the term recombinant DNA refers to the recombining of different pieces (aka segments) of DNA. Cloning refers to the process of preparing multiple copies of an individual type of recombinant DNA molecule. The classical modes for producing recombinant molecules involves the insertion of exogenous fragments of DNA into either bacterially derived plasmid (circular double stranded autonomously replicating DNAs found in bacteria) vectors or bacteriophage (viruses that infect bacteria) based vectors. The term vector refers to the DNA molecule used to carry or transport DNA of interest into cells.
Diseases of the hair follicle include alopecia areata (AA) cicatricial alopecia, and androgenetic alopecia (AGA), by far the most common disorder affecting scalp hair. In order to determine diseased genes from functional analogues, the use of recombinant DNA allows researchers to compare structural differences at a molecular level. When such differences are found they are tested to determine the potential for "loss of function" in the given gene of interest.
For instance, in 1998 researchers at Columbia University cloned "hairless" the first gene linked to hair loss. A damaged version of this gene was found to be responsible for a mouse mutation resulting in a failure to produce hair.
A nearly identical version of this gene was subsequently found to be present in a small population of people, who, like their mouse counterpart, were denuded of hair. This important first step laid a foundation stone in the groundwork for determining the underlying genetic and epigenetic nodes governing hair follicle biodynamics. Since that time, additional genes have been cloned and a rudimentary framework for how hair follicles operate is starting to take shape.
Another potentially important tool in this arena is antisense therapy. Antisense therapy is a form of treatment for genetic disorders or infections. When the genetic sequence of a particular gene is known to be causative of a particular disease, it is possible to synthesize a strand of nucleic acid that will bind to the messenger RNA (mRNA) produced by that gene and inactivate it, effectively turning that gene "off". This is because mRNA has to be single stranded for it to be translated. Alternatively, the strand might be targeted to bind a splice site on pre-mRNA and modify the exon content of an mRNA.
This synthesized nucleic acid is termed an "anti-sense" oligonucleotide (oligo) because its base sequence is complementary to the gene's messenger RNA (mRNA), which is called the "sense" sequence (so that a sense segment of mRNA " 5'-AAGGUC-3' " would be blocked by the anti-sense mRNA segment " 3'-UUCCAG-5' ").
Antisense drugs are being researched to treat cancers (including lung cancer, colorectal carcinoma, and other melanoma and other cancers. Antisense is also finding application in diseases caused by inflammatory factors. These include diabetes, amyotropic lateral sclerosis, asthma, arthritis and, potentially certain forms of hair loss, including AA. Most putative therapies have not yet been tested in human clinical trials, though once the basic science proof-of-principle research is completed, human trials will constitute a logical next step.
In our next article on the future of hair loss research we will explore hair cloning.
