Avacor® Hair Regrowth Blog
27Sep/110

Future of Hair Regrowth (Part 3)

Part 3 – RNA Interference

Another possible strategy for combating androgenetic alopecia in the future could involve harnessing a molecular phenomenon known as RNA interference (RNAi) to block the expression of the genes that cause hair loss in the first place.

Avacor Blog - What is mRNA?Molecular Biology 101: What is RNA?

Ribonucleic acid (RNA) is a biological polymer that is essential for all known forms of life. One type of RNA, known as messenger RNA (mRNA), carries genetic information derived from DNA (the master genetic "blueprint") out of the cell nucleus to the cytoplasm where it is translated into proteins (e.g., receptors or enzymes).

(For more details on RNA check out the entry on Wikipedia.)

The Science Behind RNAi

Years of research on gene expression in plants, worms, and eventually mammals, have led to the understanding that small fragments of nucleic acids like RNA can specifically block the production of any given protein in a cell.1

Small interfering RNAs (siRNAs) are short fragments of RNA, approximately 19-23 nucleotides in length, which recognize and bind to specific sequences in a target mRNA and recruit RNAi machinery (including an enzyme called "Dicer") that chop up the target mRNA. Once the mRNA is cleaved, it can no longer be translated into the corresponding protein it encodes. With the sequencing of the human genome completed, siRNA sequences can be designed to specifically target almost any gene.

RNAi technology could be utilized in the context of treating androgenetic alopecia to inhibit the production of proteins that are involved in hair loss or that slow the growth of hair.

Given the widely recognized role of dihydrotestosterone in hair follicle miniaturization and pattern hair loss, two particularly attractive targets for RNAi therapy are the androgen receptor (AR) and the 5-alpha reductase enzymes.

(For background information on DHT, AR, and 5-alpha reductases in hair loss, see our previous posts on anti-androgens here and here.)

Avacor Blog - How RNAi Works
This strategy is supported by several scientific papers, including one published in 2009 that focuses on blocking expression of AR:2

“Antiandrogen therapeutic oligonucleotides targeting the downregulation of the AR expression is advantageous because both will be possible to eliminate the only way for androgens to act and simultaneously this strategy allows the medication to be topically administrated. In fact, this could be very useful in a long-term treatment of, for instance, androgenetic alopecia...”

A Possible Manufacturer?

A company called Sirna Therapeutics described just such an approach in a patent application, published in 2005 as US 2005159376 A1. In the application, Sirna suggested using siRNA targeting either AR or 5-alpha reductase to treat alopecia:

“Specifically, the invention relates to small nucleic acid molecules [...] capable of mediating RNA interference (RNAi) against 5-alpha reductase and/or androgen receptor. Such small nucleic acid molecules are useful, for example, in providing compositions for treatment of traits, diseases and conditions that can respond to modulation of 5-alpha reductase and/or androgen receptor expression in a subject, such as alopecia, acne, polycystic ovary disease, prostitic hypertrophy, and prostate cancer.”

Since RNA does not cross the cell membrane or the skin barrier efficiently, one approach for delivering siRNA molecules is to encapsulate them in a sphere of "phospholipids" similar to those that make up the cell membrane. These spheres, known as liposomes, would cross through the skin and facilitate the entry of siRNA into the desired cells in the hair follicle.

“The siNA molecules of the invention are added directly, or can be complexed with cationic lipids, packaged within liposomes, or otherwise delivered to target cells or tissues. The nucleic acid or nucleic acid complexes can be locally administered to relevant tissues ex vivo, or in vivo through direct dermal application, transdermal application, or injection, with or without their incorporation in biopolymers.”

Here is an example of how such a treatment might be delivered:
Avacor Blog - Treating Alopecia with RNAi

Not Quite There Yet

While the approach outlined above will theoretically be effective as a treatment for androgenetic alopecia, some details still need to be worked out. Delivery with simple liposomes works very well in cell culture models, but may not be as effective in the more complex environment of the skin. According to a review article published this year:

“More efficient drug delivery vehicles are therefore being sought. Among the newly emerging concepts, drug delivery systems based on nano- and microparticles, which efficiently penetrate via the follicular route, are highly promising approaches.”3

“Nevertheless, this is still a very incipient area that promises to bring new and highly targeted strategies for skin and hair diseases.”

As with all the other treatments described in this series of posts, any therapeutic strategy would need to be tested in clinical trials to make sure it is safe and effective before approval by the FDA.

Thanks again for joining us this week as we look into The Future of Hair Regrowth. Don't forget to come back soon for the next installment in the series, which will cover what may be the most promising area in hair growth research today: stem cells.

_________________________

1. Zamore PD, Tuschl T, Sharp PA, Bartel DP. RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell. 2000 Mar 31;101(1):25-33. Link to PubMed

2. Dugour A, Hagelin K, Smus C, Balañá ME, Kerner N. Silencing the androgen receptor: new skills for antiandrogen oligonucleotide skin and hair therapy. J Dermatol Sci. 2009 May;54(2):123-5. Link to PubMed

3. Araújo R, Fernandes M, Cavaco-Paulo A, Gomes A. Biology of human hair: know your hair to control it. Adv Biochem Eng Biotechnol. 2011;125:121-43. Link to PubMed