4 patients with severe alopecia areata symptoms had a hair volume before and after treatment with barritinib (left) and after treatment (right). Image courtesy of Yale University
Encountering alopecia areata is almost equivalent to disfigurement. Sadly, only a small number of people recover spontaneously and there has been no cure. However, in an unexpected attempt, Yale scientists found a cure for the disease, making 1/3 of the patients better.
If the loss of hair volume makes people feel sad slowly, the feeling of alopecia Areata is more like a momentary crushing of people's hearts. It happens so suddenly that it is described to have only a slight tingling sensation before it happens, but it results in an almost "disfiguring" result — a piece of hair in an oval or circular area that falls off completely.
Scientists have been studying alopecia areata for a long time, and some good news is that after a few years, some patients will lose their hair and grow back, and alopecia areata will disappear. There are also ways to help treat alopecia areata, such as topical glucocorticoid injections in the area of hair loss. But the bad news is that none of these methods can completely cure alopecia areata, and one in 50 people will develop alopecia areata at some point in their lives. Alopecia areata occurs at any age, but is more common in young adults (younger than 40 years).
For patients with severe alopecia areata — such as alopecia areas concentrated in the hairs on the top of the head, to large areas of hair loss throughout the body — the chance of complete recovery is usually less than 10%. In addition to this, some treatments that promote hair growth, there are also some side effects, such as causing patients to experience more severe hair loss after recovery. Thus, alopecia areata is not a simple disease – it all begins at the moment when the hairs on the surface of the human body lose their immune privilege.
Immune privilege
Some areas of the human body have immune privilege, in other words, although antigens (such as cytopathies, viruses, bacterial invasions, etc.) are present in some tissues and organs, there is no violent immune response. In fact, this is to protect cells that have critical functions but are fragile. A common example is the eye, where the suitability of donors and recipients is generally considered when performing organ transplants, while corneal transplant rejection is low because there are few immune cells in this area. Similarly, the brain and uterus also have immune privileges, which are achieved through the blood-brain barrier and the placenta, respectively. They protect neurons in the brain from an inflammatory response, and the fetus survives in the mother's body until birth.
Under normal circumstances, our hair follicles also have certain immune privileges and are not attacked by immune cells. The hair follicle is composed of three main parts, namely hair papilla, hair matrix and hair bulb. Hair papillae are located at the very bottom of the hair follicle and are mainly blood vessels and connective tissue. The hair matrix wraps around the hair papilla, which contains Trichocytes, which are involved in the formation of hairs and nails. Then there's the hair ball, which contains a variety of stem cells that supply new cells to the entire hair follicle and promote wound healing.
In alopecia areata patients, immune cells mainly attack the hair papillae, which in turn leads to hair loss. Image source: Wikipedia
From the 20th century onwards, the scientific community gradually recognized alopecia areata as an autoimmune disease. Alopecia areata appears because a variety of immune cells are involved in besieging the cells at the base of the hair follicle, including helper T cells, cytotoxic T cells, and natural killer cells. They trigger an inflammatory response in the area of the hair follicle, which in turn leads to hair loss, but because it does not damage the area of the hair bulb containing stem cells, the hair follicle is theoretically regeneratible.
The genes behind alopecia areata
In 2010, in a study published in the United States, scientists at Columbia University and other institutions in the United States performed whole genome sequencing of 1,054 alopecia areata patients and more than 3,000 ordinary people, analyzing possible gene expression abnormalities in alopecia areata patients. They found 139 single nucleotide polymorphisms associated with alopecia areata (there are 139 variations caused by a single nucleotide mutation).
Judging by these single-gene mutations, the appearance of alopecia areata is both the responsibility of the immune system — especially the regulation of T cells — and the problem of hair follicles. They found genetic variants that also occur in other autoimmune diseases, such as rheumatoid arthritis and type 1 diabetes, including CTLA4, IL-2/IL-21, IL-2RA, and genes that regulate T cell activation and proliferation. Among them, regulatory T cells play a key role in inhibiting processes such as immune cells attacking their own tissues.
In addition to this, they also found a ligand molecule NKG2D induced by pressure. For natural killer cells, natural killer T cells, and other lymphocytes, this molecule is a red flag, so they attack the cells that express it. Cells in the hair papillary region of many alopecia areas are highly expressive of this molecule. This may explain why stress can lead to alopecia areata. This condition also occurs in autoimmune diseases such as rheumatoid arthritis and type 1 diabetes.
New attempts
Because of this, some scientists want to treat hair loss with drugs that treat rheumatoid arthritis. Although it seems that the wind and horses are not comparable, but because the internal pathogenic mechanism of the disease is the same, it can still be tried. So what about the results of clinical trials? Recently, in an article published, researchers at Yale University, Stanford University and other institutions confirmed through clinical experiments that a drug for the treatment of rheumatoid arthritis can make 1/3 of alopecia areata patients grow their hair again.
Brett A. King, associate professor at Yale School of Medicine (Image: Yale School of Medicine website)
The whole story begins around 2014. At the time, Brett A. King, an associate professor at Yale School of Medicine, received a patient. The patient suffered from both diseases, psoriasis and alopecia areata, when he lost his eyebrows, eyelashes, armpits, and hair on his head, and only had hair in the reddened area where psoriasis appeared. King tried to treat the patient's symptoms with a drug that had been approved by the FDA, tofacitinib citrate. He was confident in the drug, believing that it could treat both psoriasis and alopecia areata. However, at that time, it was only confirmed through mouse experiments that tofatinib citrate could treat alopecia areata.
As a result, this patient was very fortunate to be the first patient to recover from alopecia areata after treatment. After 8 months of treatment, all the hair he had lost had grown back and in large quantities. After this success, King wanted other alopecia areata patients to benefit from the drug, so he conducted a major clinical study.
The patient, who suffered from both psoriasis and alopecia areata, regained his thick hair after receiving treatment with tofatinib citrate. Image courtesy of Yale University
Fast forward to 2016, and their clinical trial of treating 66 alopecia areata alopecia areata patients with tofatinib was also a great success. The side effects of the drug are minimal, and after taking it (5 mg 2 times a day) for 3 months, more than half of the patients have hair regrowth, and 1/3 of the patients have recovered more than 50% of the hair they have lost.
In the recent new study, they tested a drug similar to tofacitinib, baletinib, both of which are JAK1 inhibitors, and in the clinic, the treatment of rheumatoid arthritis is comparable, both of which can prevent immune cells from damaging hair follicles by interfering with their communication.
This time, they conducted a total of 2 large clinical trials, enrolling 654 and 546 alopecia areata patients, respectively. These patients all have more severe alopecia areata symptoms, and if their symptoms are scored, 0 and 100 refer to no hair loss and total baldness, respectively, they are in the range of 50 points and above. Participants were randomly assigned to the 4 mg, 2 mg, and placebo groups on a 3:3:2 ratio and received treatment for up to 36 weeks.
They found that in the first trial, 38.8 percent of people in the 4 mg group and 22.8 percent, respectively, recovered symptoms from 50 points and above to 20 points and below after treatment, arguably recovering more than half of the lost hair, compared with only 6.2 percent of those in the placebo group who recovered to this extent (people who can be considered to have recovered naturally). The results obtained in another trial were roughly comparable to those obtained from this trial.
King said: "Suffering from alopecia areata is very sad for many people, and confusion, confusion and deep sadness are the hallmarks of this period. It would be incredible if there was a drug that would help people get out of it, get back to normal, and get themselves and those around them to reacquaint themselves. "For the past decade, King has been experimenting with JAK inhibitors to treat a variety of skin conditions, including eczema, vitiligo, ring granulomas, sarcoidosis and more. As we learn more about these diseases, we will also be able to effectively help more people who suffer from these diseases.
thesis:
https://www.nejm.org/doi/10.1056/NEJMoa2110343
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921172/#R4
Reference Links:
https://www.sciencealert.com/common-arthritis-drug-shows-promise-for-treating-severe-alopecia-in-clinical-trials
https://en.wikipedia.org/wiki/Immune_privilege
https://en.wikipedia.org/wiki/Hair_follicle
https://news.yale.edu/2022/03/26/new-trials-alopecia-areata-treatment-are-success
https://news.yale.edu/2016/09/22/hope-patients-hair-loss-arthritis-drug-spurs-regrowth
https://news.yale.edu/2014/06/19/hairless-man-arthritis-drug-spurs-hair-growth-lots-it