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Double Stranded RNA Archives | Hair Loss Cure 2020 Update: April 27, 2020
Dermatologist Dr. Luis Garza from John Hopkins Medicine is among the 10 most renowned hair loss researchers in the US. Both the general media and myself have not covered him anywhere near as frequently as we have others. Especially compared to the “Big Three” of Angela Christiano, George Cotsarelis and Ken Washenik.
However, as a hair loss researcher, I respect Dr. Garza more than any other leading scientist. Primarily because he seems to have stuck with one institution for most of his career. And he does not seem to be affiliated with various commercial interests. Dr. Garza is especially well known for his work with PGD2 and hair growth.
Dr. Luis Garza Recent Interview Yesterday, I discovered a great recent video interview of Dr. Garza with ideaXme’s Ira Pastor. It only had 508 views at the time of writing this post, so was missed by most people. Youtube has a goldmine of such barely viewed content that does not show up when people sort by view count.
At the moment, the below video has 25 thumbs up votes and 0 thumbs down votes. I agree with this percentage. This is the first time that I have seen Dr. Garza on video, which is very surprising to me.
Among the most interesting parts of the below video include:
Double-stranded RNA (dsRNA) and its influence on scarless wound healing and hair regeneration. Wounding and hair growth aka wound induced hair neogenesis. Genes involving dsRNA and genes involving skin retinoic acid production are both expressed at higher levels after laser treatment. Organogenesis and limb regeneration to help the wounded. The connection and similarities between hair regeneration, skin regeneration and organ regeneration. Cells have a GPS type homing mechanism that tells them where to go and how to behave.
August 6, 2015
I have discussed Dr. Luis Garza’s work on this blog several times before, mostly related to his important findings about prostaglandin D2 (PGD2) and its impact on hair growth. Dr. Garza is among the most accomplished and respected hair loss researchers in the world. He works at the Johns Hopkins University School of Medicine. In fact he has his own named facility there called the Garza Laboratory . The list of projects that his team is currently working on includes several focused on hair growth.
Toll-Like Receptor 3 and Double-stranded RNA Today, Dr. Garza and his team published an important article in the Cell Stem Cell Journal. They have found that a protein called toll-like receptor 3 (TLR3) plays a crucial role in the regeneration of damaged skin and hair follicles. TLR3 activates various genes (IL6 and STAT3) and signaling pathways (Wnt and Shh) that are involved in hair regeneration.
It is common knowledge that damaged mammalian skin releases double-stranded RNA (dsRNA), which is then sensed by TLR3. Besides the previously mentioned regeneration of damaged skin and hair follicles, TLR2 also plays a role in activating the immune system.
While most of the main work was done on mice, in a side experiment on humans, the Garza team found that “the expression of TLR3 was five times higher in scratched human skin cell samples compared to healthy skin cell samples.”
The Garza team also found that adding synthetic synthetic dsRNA to mouse skin wounds led to a greater number of regenerated follicles.
My two favorite quotes from Dr. Garza in the article:
It has long been known that skin damage can trigger regeneration.
The clinical translation of this work is promising because work has already started, says Garza. Drug companies are already developing products to activate TLR3 to trigger the immune system, and these same products could be tested to promote regeneration.
My least favorite quote from Dr. Garza in the article (although the “might” in there is encouraging):
He also made clear that the information might not be as applicable to conditions unrelated to scarring or to those whose hair follicles are lost from male pattern baldness.
Hair loss news first:
BiologicsMD On July 30, it was announced that the University of Arkansas (along with several other entities) was issued a patent for a new hair loss drug based on work done by Dr. Joshua Sakon and three others. The patent is titled “Fusion Proteins of Collagen Binding-Domain and Parathyroid Hormone.”
Arkansas based privately held BiologicsMD holds the exclusive license to this technology. Their related hair loss drug will be known as BMD-2341. The related patent issued by the US Patent and Trademark Office is No. 9,062,300. The main portion of BiologisMD’s work entails bone growth, including for the spine, fracture repair and osteoporosis.
3D Printed Comb from Technion University I am surprised that there has not been much new research coming from Israel when it comes to hair loss. The country has a booming start-up scene, and from my observations, Jewish people seem to suffer from baldness at an even higher rate than Caucasians (who in turn have much higher rates of baldness compared to Asians). In any case, this new 3D printed comb for hair loss project from Technion University in Israel seems interesting (you need to translate), although I would not be surprised if we never hear about it again. FYI — For any readers in Israel, here is an article from 2011 with names of local hair loss experts and clinics that you could consult.
Lumigan for Thicker Eyebrows For several months, Spencer (aka Spex) has been experimenting with using Bimatoprost on his previously sparse eyebrows . He uses the Lumigan brand that is designed to reduce high pressure in the eyes. He recently added the above page on his site, and it is well worth checking out the before and after photos on there. Many hair loss sufferers have been waiting for months to hear about the delayed results of the clinical trials of Bimatoprost when used on scalp hair. While I have been skeptical that the drug will do much beyond what Minoxidil already does for scalp hair, Spex’s eyebrow results are very encouraging. Bimatoprost, if approved for use on the scalp, will entail a drastically higher dosage compared to what is used on eyebrows.
Other Hair Loss News this Month — A very interesting radio interview with Dr. Luis Garza regarding his team’s latest groundbreaking findings on triggering organ and hair regeneration. See my recent post on those findings.
— Samumed is recruiting for a 50-person supplemental clinical trial for its SM04554 .
— George Cotsarelis gets yet one more patent approved (this one related to FGF-9 and hair growth). Filed in October 2014 and approved in August 2015.
— An optimistic conclusion from a molecular biologist: “In any case, I think that treatment for baldness is now a matter of quite a short period of time .” Article rambles a bit, perhaps because the writer is not a native English speaker.
— Some interesting thoughts on platelet-rich fibrin matrix from Dr. William Lindsey .
— In June, Dr. Alan Feller started a controversial thread on the HTN forum regarding strip (FUT) hair transplants still being more popular than FUE hair transplants. That thread has taken on a life of its own, and I only read it this month since I do not frequent those forums too often. Based on my own research (see FUE versus FUT hair transplants ), I do not believe that strip will remain very popular. It already might be less popular than FUE, considering that doctors can now just purchase the ARTAS robot. They can then start practicing FUE with little past experience in doing so. In any case, Dr. Feller raises some interesting points in that thread, and I wonder if FUE transaction rates are really that high in the hands of experts? If I was getting a hair transplant today, I would go for FUE.
— A very useful update from a Japanese resident regarding AAPE and HARG treatment in Japan .
— An interesting study (on mice), where pluripotent stem cells from whisker follicles differentiate and grow into new hair when transplanted to the spinal cord.
— Comedian Matt Lucas has suffered from alopecia universalis for most of his life. A nice story on him helping a young boy suffering from the same here .
— Somewhat related to the above, scientists use cells created from hair follicles to repair damaged nerves .
And now on to medical items of interest:
Things are getting creepier and creepier and at the same time evermore mind-boggling each month.
—Nearly complete brain developed in petri dish by Ohio State scientists . This was major news yesterday and today.
— United Therapeutics (Revivicor) is genetically engineering pigs in order to transplant their organs into humans . I find it absolutely fascinating that you can insert human genes into animals and that scientists are able to increase the number that they can insert every year. The founder and CEO of United Therapeutics is the amazing MTF transsexual Martine Rothblatt , who also co-founded Sirius XM satellite radio.
— Young blood is what we all need .
— Body-hackers . Worth clicking just to see the image.
— A pro designer baby article worth a skim-through. The Chinese will probably stab at this first.
— A list of the top 11 3D-Bioprinting companies .
Hair loss news blog. Hair cloning for baldness.