Ideas for the Near Future

[Tobias]

Hi,
I was just reading the forum every now and then so far, but now I feel like I should contribute something as well.
I am a fifth year medical student and have done some in vitro research on lymphoma therapy so far. So I have a rough understanding of our field.

For everyone who is crying that there wont be a treatment in sight for the next 15 years, I want to say that hundreds of new drugs are tested in clinical trials at every given moment for all kinds of diseases. It is not unlikely that one of them shows the side effect of preventing loss or inducing regrowth. In the field of rheumatology a wide variety of completely new anti-inflammatory drugs are comming to the market (TNF-alpha inhibitors, IL-17 inhibitors, Il-6 inhibitors etc.) for exemple.

However, for those who are a little comfortable with the scientific side of it, I want to discuss or share an idea, that I myself most propably won´t pursue but that will surely offer a solution in the future.

The cure for hair loss is already found: it is simply to prevent the hair follicles from reacting with dht/testosterone. Women don´t get MPB and castrated men neither. The problem so far is simply that any treatment that prevents this interaction is not specific enough to the scalp or hair follicles. Every anti-androgen (Finasterid, Sm, Ru (the things some of you are experimenting with) will effect the whole body in some way and thereby leading to side effects that no one wants to risk (ED, depression, loss of sex drive, infertility).

So the problem is not that we dont know how to cure it, but that we don´t know how to get a scalp specific anti-androgenic effect. Its a problem of drug delivery. Nothing else.
Any topical solution that somehow enters your body will enter your blood stream and therefore end up in the whole body.

A possible solution (I am just pointing into a direction with this, nothing else):

Create a window of opportunity to induce a permanent change of the androgen-response of hair follicles, in which the rest of the body is not affected.

A permanent change can be attained by site-directed mutagenesis. One could use RNA/DNA oligonucleotides to induce single nucleotide mutations in the gene of the androgen receptor (roughly 400 mutations are known from people with adrogen insensitivity). This method works in vitro. The efficiency of the delivery of the oligonucleotides to the cells of the human hair follicle will depend on an appropriate vector (extensive research is done in this field!) and different options are available.

The exposure of the hair follicle(-cells) to our vector has to happen in a setting where there is no connection to the circulation system.

Option 1: extract hair follicles (like in FUE) and incubate them with the vector in vitro. If, due to low efficiency of the oligo delivery into the nucleus, several incubation periods need to be done, one could think of implanting the follicles into the skin of immun compromised mice, who will keep the follicles alive while delivering our vector through their blood stream as often as needed. Then the androgen-resistent follicles can be reimplanted into the human scalp.


Option 2:
Create a local, independant circulation of the scalp for delivery of the vector. By appling strong circular pressure around the scalp, one can shut down the escape of blood from the scalp. Then one has to connect the bigger veins and arteries within this area of the scalp to a miniature ECMO machine (which is a machine that gives oxygen to the blood and has a little pump to creat a blood flow. So it is an artificial lung and heart which is usually used when the heart is out of order during surgery or at the intensive care units). This way, we create an isolated circulation of the scalp for a long time. During this time, we can deliver any drug or vector we want in high doses specifically to the scalp. If the effect of this drug is permanent (like the gene therapy mentioned above, it is a cure).

I know that gene therapy is only FDA approved for one disease so far and that the big problem is the effiency of delivery as well as safety (usually the vector is a virus). But the hair follicle has the big advantage, that it can be taken out the body easily (or "isolated" within the body) and treated there. Kind of like they do it with stem cells of the blood already. The problem there is, that the effciency is too low. But in the mouse option, one could repeat the treatment over and over again until the desired efficiency is achieved.

So bottom line: a cure is not that impossible after all. Every research that is done right now will contribute to finding a good cure for hair loss. Everyone who want to now if something good for mpb is happening, should keep a close eye on the development of drug delivery in gene therapy and cancer treatment. Thats where the big fundings go and thats where I think a cure can come from.

Additional idea:
-An antiandrogen that transiently changes to its active conformation during exposure to UV or infrared light exposure (also not impossible. One would have to wear a head with lights in it during the night

Cheers