Anti-Aging Peptide, Replicel Check-In: Weekly Thoughts 4/7/17

Hello Everyone,

It is good to be back for another Weekly Thoughts. This edition is headlined by an anti-aging technology from The Netherlands that has shown interesting regenerative effects on mice. I even got some exclusive info on the potential of this technology to be applied to hair growth to share with you. Also, we get an update on how Replicel’s treatment has faired on people’s scalps five years after the injections. And while we are still looking forward to an update on a particular hair cream coming out of Turkey, I have some good news about another cosmetic hair cream that may be of interest.

Foxy Science

Researchers at the Erasmus University Medical Center have discovered a peptide capable of reversing age-related symptoms in mice. The research was led by Peter de Keizer of Erasmus. The main function of this peptide is to get “senescent” cells (cells affected by aging) to go through “apoptosis” (cellular death). Kind of like cleaning out the old cellular closet. The peptide affects the communication between two proteins – FOXO4 and p53. In this case, it blocks the signal from protein FOXO4 to p53 to tell the cell to not kill itself. When that signal is blocked, the cells revert to apoptosis and die. What is attractive about this approach is the FOXO4 protein is virtually non-existent in healthy cells, and so this treatment does not interfere with the lifespan of healthy cells, only the damaged aging cells.

And you guessed it, one of the effects that this therapy created in mice was hair regrowth. Other effects that were noted in the study included kidney function and energy level. The researchers at Erasmus are now looking into whether this therapy will also increase life-span. A human study is being planned using the FOXO4 therapy to treat a specific type of brain tumor. I read some brief comments from the leader of this research, Peter de Keizer, about using this treatment to grow hair in humans. I decided that it would be worthwhile to see if I could get a few comments from de Keizer about how close hair growth R&D really is for this peptide. I’m happy to present a brief interview with Peter de Keizer which explains what’s going on with the FOXO4 peptide currently and how he intends to use it to treat human conditions.

Exclusive interview with Peter de Keizer

FT: What is the next step in R&D for the FOXO4 peptide?

PdK: We designed this peptide to interfere with the interaction between FOXO4 and p53. We now have more structural information about this peptide and its interactions. As such, we will focus on optimizing it further. In addition, we observed that this FOXO4-peptide is effective against senescence in vivo. However, before we think we are ready for clinical translation, we will put a lot of effort into finding out how safe these compounds truly are. We observe this peptide to have a benefit in certain types of recurrent cancer. We are therefore very eager to see whether it can be employed against those initially, and when successful and safe, whether more age-related diseases could be targeted.

(In regards to hair)
Yes, we are now allowed by the ethics committee to test this peptide in a cream against skin diseases present in the fast aging mice. In the meantime, we will then of course also address (take note of) hair regrowth. The downside is that this peptide might not penetrate the epidermis and be useless as a cream. But we hope the hair follicles might enhance uptake.

FT: If the cream shows potential as a topical hair growth treatment in mice, what then would be your plan moving forward?

PdK: This is a difficult question to address. It is amazing to see that people, especially men, are most interested in the hair phenotype (hair growth effect) and less in the effects on organ function, actually. While we certainly are interested in the effects on hair (re)growth, there are more severe, and even life-threatening, diseases for which we think this might be useful too. It is too early to tell in what scenarios it is going to work best, but from an ethical point of view it would be best to start with severe disease indications. Needless to say, if the experiments with this peptide in a cream are successful, this is definitely worth pursuing.

FT: You mentioned there are many health concerns that this peptide may address, what will this peptide be used to treat first?

PdK: For now, we think that the first disease indication for which we might move to the clinic, could be some specific types of late stage, recurrent cancer. Still, much needs to be done before we are ready, including a more elaborate safety assessment, but, given that for those indications there are no alternatives and we appear to have a promising effect, this might be the first point on the horizon. Thereafter, milder age-related diseases could be targeted – provided that the compounds are deemed safe enough. Eventually, perhaps aging as a whole, but this would be in the far future.

FT: Is there anything else you’d like to announce or express at this time?

PdK: Over the last couple of years, we’ve seen some very exciting developments in the anti-aging space. For long it has been known that aging could be delayed by eating less and exercising more (or using compounds that mimic these effects as Rapalogs, Metformin or Resveratrol). To a degree it is disappointing that this was nearly the only thing that could be done. By now, it seems that it is also possible to not just stall the deterioration, but to also revert it. We showed this in the case of senescence removal and a recent paper by Ocampo et all, 2016 Cell showed that transient expression of Yamanaka factors could promote tissue rejuvenation. Altogether these three areas (delay of aging, targeting senescence and tissue rejuvenation) could be 1+1+1=6 in order to combat aging. I am very excited to see more on this in the future!

Thank you very much Peter de Keizer for taking the time to share a few words with us.

 

Replicel at 5 Years

The five year safety data of Replicel’s phase 1 clinical trial has finally been released. Man, has it been 5 years already? I guess it has. Within the five year safety data was also released the two year’s efficacy data. To be honest, the results were mostly what would be expected, based on what we already know about the treatment. From the top seven responders of the treatment, there was a >10% increase in hair density after 6 months ,and at 2 years that increase dropped slightly to 8.3% over baseline. A slight drop in density after 1.5 years seems reasonable due to the fact that the subjects were not receiving any further treatments. I was, however, surprised to read that one responder from the cohort held a 21% increase in hair density after 2 years time. That is noteworthy, folks. Another meaningful tidbit from the data is the claim that “an overall stabilization of hair loss was observed among all the patients treated per protocol.” This means some of the benefits of RCH-01 could be materializing in ways that are not recorded in statistics, e.g. the halting of the progression of hair loss.

What’s most important is that the treatment displayed a high level of safety through the five year analysis and now Replicel can look into ways to optimize the efficacy of RCH-01.

Rolf Hoffman, CMO of Replicel, has already stated: “Over the past 36 months, we have invested a great deal in both basic research and manufacturing optimization which we believe will be critical to minimizing batch-to-batch variability and further improving efficacy. We have invested in process and product development initiatives including a modified tissue culture technique, improved culture media with addition of 12 new ingredients, introduction of a cell activity promoting step, and cryopreservation storage to improve cell stability and viability. We believe these programs have already resulted in a significantly more robust and better-defined product than the one used in this trial by many measures and look forward to translating our continued R&D into next-phase clinical trials in due course.”

Now let’s see what RCH-01 can do when given in smaller doses, more frequently, over a period of time. While there is a phase 2 trial planned for Replicel in North America, there has been no set date as to when that trial will commence.

Samumed Still Thinking Phase 3

Good news was released by Samumed this past week in an online news publication. After seeing roughly a 10% increase in hair density in a phase 2 trial for its topical hair growth treatment SM04554, Samumed will continue on. During the initial phase 2 trial, a .15% solution showed better results than the .25% solution of SM04554. In a second phase 2 trial, the .25% solution showed slightly better hair growth. Now, apparently the company is planning one last phase 2 trial to get the final verdict on which % solution to use before heading into a phase 3 trial. It looks like SM04554 is destined for phase 3.

My Trial of a Cosmetic Cream

Many of you may not know that over the past year I have been trialing a cosmetic hair growth cream. The cream itself is known about online and sometime very soon I will give my full personal review of the product. I don’t want to give an exact date when, due to the possibility of a change of schedule, but the review will be out soon. I’m just waiting on info from the company. And, just in case you were wondering, no it is not the ReBoost cream. Speak to you soon.

Until next time, be well.