Immunosuppressants and Face and Organ Transplants

For many years, I have followed news in the fields of organ transplantation, limb transplantation and face transplantation with keen interest. Each year, achievements in those fields become evermore impressive. The use of immunosuppressants is also becoming safer and more strategic.

Scientists and doctors in countries as dispersed as China, India, Japan, Spain, Thailand, Turkey and the US all seem to be producing groundbreaking results and innovations in the field of transplantation.

Worldwide Face, Organ and Limb Transplants

Most developing countries do not have sizable local biotech and other new-age industries. However, the vast majority have numerous hospitals, usually including at least several world class ones. Poor citizens in third world countries often have no choice other than to get transplants at local hospitals. This enables local doctors and surgeons to gain significant experience in organ transplantation.

In the field of heart transplantation, India is especially important. In the field of full face transplantation, while the US leads the way, Turkey is also very important. The world’s first face transplant was done in Spain in 2010. China has also achieved some significant milestones in face transplants. It is supposedly also the first country where a penis transplant was successfully undertaken. Unfortunately, the patient did not want it after all that hard work and stress! You can read about the latest developments in Japan towards the bottom of this post.

One frequent question on hair loss forums is why people with significant balding and limited donor hair do not get hair transplants in which the donor hair comes from another person. Update: see allogeneic hair transplantation success.

The reason given is that in order for such a procedure to be successful, one would have to take immunosuppressive drugs (i.e., anti-rejection medicine) for a lifetime. This is not a risk worth taking for a cosmetic problem such as hair loss. Perhaps person-to-person hair transplants are also far more complex, since each hair being moved is a unique organ?

Immunosuppressants after Organ Transplants

Like almost anyone else, I feel that taking immunosuppressive drugs to get hair transplanted from another person was foolish. However, recently, I started getting curious as to how dangerous these immunosuppressive drugs really turn out to be.

Do people below the age of 65 die more frequently from diseases and infections after organ transplantation? Is it because their immune systems become weaker when they are on immunosuppressants?

Although I could not find too much information on fatalities, there are quite a few sites with warnings about side effects of taking these drugs. A large number of side effects are not especially dangerous, but there are some warnings of potential higher risks of cancer. However, this correlation with higher rates of cancer is not entirely clear cut.

One surprising thing I found was that immunosuppressants are often even prescribed for problems such as Eczema and Psoriasis for people with severe cases of these skin cell disorders.

It should also be noted that scientists have increasingly improved strategies in having organ transplant recipients taper off high-dose immunosuppressants. Not to mention the availability of new drugs, biologics and immunosupresssants.

Interesting Organ, Limb and Face Transplant Results

The duration of time for which organ transplants last has in general gone up for all organ types over the years. Some of the unexpectedly long-lasting results are particularly interesting. Especially when considering that the patient has to take immunosuppressant drugs throughout his or her life. Usually at a lower dose after the first year or so post transplant.

Some of my favorite recent transplant related stories:

British grandmother whose new kidney was still going strong 40 years post transplant as of 2014.

When it comes to the heart, Dick Cheney should be inspirational to all. Money and access to great surgeons helps of course. But rather then being envious, for the sake of science I hope that this man lives many more years. A good post transplant interview with Cheney.

US man with rare double hand transplant in 2010 still going strong five years later.

Heart transplant at the age of 2, still here at 32 as of 2014.

British man breaks world record in 2013 after surviving 31 years post heart transplant.

US face transplant recipient Mitch Hunter’s excellent Reddit “Ask Me Anything.” Also see photos: Soldier Mitch Hunter.

Setipiprant Global Rights Purchased by Kythera

Update: October 2021 — Unfortunately, the clinical trials of Setipiprant for androgenetic alopecia saw no hair growth benefits. The trials were conducted by AbbVie (US), which purchased Allergan in 2020.

Kythera audio interview with founder and CEO Keith Leonard regarding Setipiprant. Plus the company’s recent history of hair loss research is now out. Excellent stuff.

Setipiprant Rights Purchased by Kythera (now Allergan)

A thus far barren February when it comes to significant hair loss research developments suddenly changed drastically today. It was announced that Kythera Biopharmaceuticals (US) has purchased global rights to Setipiprant, a clinical-stage oral antagonist to the prostaglandin D2 (PGD2) receptor.

The shareholder presentation on this is a must read. Rights were purchased via licensing agreements with Actelion Pharmaceuticals (Switzerland) and the University of Pennsylvania. A good summary is here, with a very encouraging quote from Kythera’s Chief Medical Officer:

Setipiprant is believed to directly affect this hair loss pathway, and our own preclinical and in vitro human hair models confirmed this effect. It is a well-characterized molecule with a large safety database and we believe we can quickly initiate a development program to study it in hair loss.

Setipiprant Trials

According to the investor presentation, Setipiprant has already undergone 8 clinical trials, including:

  • A Phase III study in seasonal allergic rhinitis patients.
  • A Phase IIB proof of concept study in asthma patients.
  • A safety database of over 1,000 subjects.

One other item in the investor presentation that I found shocking (in a very good way) was that Actelion owns 45 patents that were granted for molecules that inhibit PGD2. So Setipiprant is just one molecule of perhaps dozens or even hundreds that can inhibit PGD2.

There must be other companies that also have patents to proprietary PGD2 antagonist molecules. I wonder if they can introduce their products into the hair loss market in future if they do not have licensing agreements with the University of Pennsylvania?

PGD2

PGD2 has been in the news a lot in the hair loss world during the past several years. This is in large part due to Dr. Luis Garza’s work and excellent publicly available 2014 paper on the subject. And also due to the past work of Dr. George Cotsarelis and his team at the University of Pennsylvania.

Both Cotsarelis and Garza were part of a large group of authors of an important 2012 paper which concluded that PGD2 inhibits hair growth and was elevated on the scalps of balding men. Together, these two men are also considered to be co-inventors/co-founders of this PGD2-receptor pathway that inhibits hair growth. The patent for this technology is owned by the University of Pennsylvania, hence their involvement in this current transaction.

It seems like the PGD2-GPR44 pathway (PGD2 binds to the GPR44 receptor) is responsible for hair growth inhibition, and any drug to regrow hair will target GPR44. More significantly, PGD2 is also involved in asthma, allergies and related medical disorders. In fact a number of drugs targeting PGD2 are already in advanced clinical trials or even on the market, so there should already be a good deal of safety information on this type of product.

I found seven studies on Setipiprant on Pubmed as of today. Also, some popular media articles from 2012 on PGD2 and a hair loss cure are worth a reread: Dailymail,  The Telegraph and NY Times. Unfortunately we are still not close to getting a topical lotion cure, since Setipiprant is an oral medication.

For the neglected female readers of this blog, it seems like there is a very good chance that this same drug could also cure female pattern hair loss. PGD2 appears to curtail hair growth in both men and women.

Finally, a bit about Los Angeles area based publicly traded Kythera from their website. Where else would one expect a biopharma company to focus on eliminating double chins?

Our product candidate, ATX-101, is a potential first-in-class, injectable drug currently in late-stage clinical development for the reduction of submental fat, which commonly presents as an undesirable “double chin.” We maintain an active research interest in hair and fat biology, pigmentation modulation and facial contouring.