Newly Discovered Genes Could Change Vitiligo Treatment

 

A recent study has revealed 135 previously unknown genes that play important roles in regulating melanin production in humans—and that could lead to melanin-modifying drugs for vitiligo and other pigmentation diseases.

The research team was led by Vivek Bajpai, assistant professor in the School of Sustainable Chemical, Biological and Materials Engineering at the University of Oklahoma, with collaborators from Stanford University, where Bajpai did postdoctoral work.

Melanin synthesis is compartmentalized within the melanosome, in specialized pigment cells (melanocytes). The synthesis of melanin within the melanosomes varies, which is why human skin, hair, and eye color vary. Pigmentation-related diseases are associated with disruptions in melanogenesis.

Melanin’s particular physicochemical properties, such as high refractive index, determine its optical properties, the researchers wrote in their article, published in Science on Aug. 11. “We reasoned that an accumulation of melanin within melanosomes would change melanocytes’ light-scattering properties.”

Bajpai developed a novel method to detect and quantify the melanin-producing activity of melanocytes: Passing light through the melanocytes, he could record whether the light was absorbed or scattered by the melanin. “If there are a lot of melanin-producing melanosomes,” he said in a University of Oklahoma press release, “the light will scatter much more than in cells with little melanin.”

The team measured light scattering through flow cytometry, capturing “dynamic shifts” in melanin levels within melanosomes. They used CRISPR-Cas9 technology to genetically engineer cells, and conducted a genome-wide genetic screen, systematically removing more than 20,000 genes from hundreds of millions of melanocytes.

Their screen identified 169 genes, including some that were previously known and 135 new melanin-promoting genes whose deletion was associated with reduced light scattering—in other words, loss of melanin.

The melanin-promoting genes are involved in diverse biological pathways, such as transcription regulation, RNA processing, and endosomal transport, the researchers say. “Consistent with their melanin-promoting role, the expression of the majority of our screen hits is elevated in darkly pigmented, compared with lightly pigmented, human melanocytes. Our analyses revealed that select melanin-promoting genes are associated with skin color variation and show evidence of local adaptation in human populations.”

By focusing on specific previously unidentified candidates, the researchers say, “we implicated a new cargo recycling pathway in melanosome function and identified a transcription factor involved in melanosome maturation. Our work provides a rich resource for further studies of melanogenesis and its relationship with skin color variation and human diseases.”

Their findings are also meaningful to a broad swath of science beyond dermatology. Bajpai’s method of targeting melanin-producing genes could lead to prevention of fungi- and bacteria-related diseases in humans and crops.

Reference: https://www.managedhealthcareexecutive.com/view/newly-discovered-genes-could-change-vitiligo-treatment

Cilt rengiyle ilişkili 135 yeni gen tespit edildi

 

İnsanlara cilt rengini veren pigmentasyonla ilgili 135 yeni gen tanımlandı. ABD'de yapılan araştırmadaki bulguların cilt kanseri ve vitiligo tedavilerinde yeni ilaç ve yol arayışına yön vermesini bekleniyor.

News Medical Life Sciences; Oklahoma Üniversitesi'nden Vivek Bajpai ve Stanford Üniversitesi'nden araştırmacılar tarafından yapılan çalışmada, insanlara cilt rengini veren pigmentasyonla ilişkili 135 yeni gen tanımlandığını yazdı. Araştırmacılar, cilt pigmenti de olarak da tanımlanan melanin üretimini etkileyen, işlevsel olarak farklı 169 gen bulurken bunlardan 135'inin daha önce pigmentasyon ile ilişkili olmadığı tespit edildi.

Araştırmaya göre, yeni keşfedilen KLF6 ve COMMD3 isimli iki genden KLF6 isimli DNA bağlayıcı protein, insanlarda ve hayvanlarda melanin üretimi kaybına yol açarken diğer türlerde ise melanin üretiminde rol oynuyor. COMMD3 ise, melanozomların asitliğini kontrol ederek melanin sentezini düzenliyor.

Cilt kanseri araştırmalarını etkileyecek

Bajpai, çalışmayla ilgili "Melanini neyin düzenlediğini anlayarak daha açık tenli insanları melanomdan veya cilt kanserinden korumaya yardımcı olabiliriz. Bu yeni melanin genlerini hedefleyerek vitiligo ve diğer pigmentasyon hastalıkları için melanin değiştiren ilaçlar da geliştirebiliriz" açıklamasında bulundu. Araştırmacılar, bu tür melanin üreten genleri keşfederek mikroplara ve hastalıklara karşı etkili müdahaleler geliştirebilir. Araştırma, Journal Science  adlı dergide yayımlandı.

Kaynak: Gazete Oksijen

Vitiligo Clinic and Research Center at UMass Chan to coordinate $3.75 million remote clinical study

 

Researchers at the University of Massachusetts (UMass) Chan Medical School are currently embarking on a multi-million-dollar clinical study aiming to identify the biological and molecular signatures that may predispose at-risk individuals to developing vitiligo.1

The $3.75 million study is being funded by the National Institute of Allergy and Infectious Diseases and is led by John Harris, MD, PhD, chair and professor of dermatology and director of the Vitiligo Clinic & Research Center; Manuel Garber, PhD, professor of molecular medicine, a member of the Program in Bioinformatics and Integrative Biology, and director of the Bioinformatics Core at UMass Chan; and Medhi Rashigi, MD, assistant professor of dermatology.

The researchers note that after the first year of vitiligo treatment, depigmentation is likely to return in as many as 40% of patient cases. This is compounded, they say, by a scarcity of samples and data from a cohort of patients who are representative of the collective of those with the condition, despite a significant link between genetics and vitiligo.1

Study enrollment began on June 25, 2023, or World Vitiligo Day. Over the course of the next 5 years, researchers hope to enroll around 1,000 participants in the study, which will be conducted entirely remotely. It is anticipated that of these 1,000 participants, 200 will have a clinical vitiligo diagnosis, while the remainder of participants will be family members or direct blood relatives of those with vitiligo.

Because of the link between genetics and vitiligo, Harris, Garber, and Rashigi say that they anticipate between 40 to 60 of the 800 familial participants without vitiligo will develop vitiligo at some point throughout the study’s duration.

Sampling will be conducted on a semi-annual basis, with participants being asked to complete questionnaires and submit blood, saliva, and skin tissue samples every 6 months. The questionnaires will garner data related to patients’ health, diet, and overall lifestyle. Researchers will examine the samples and questionnaire outcomes to identify environmental and outside factors, disease onset and severity, antibodies, biomarkers, and subclinical signatures of disease.

“Using this information, clinical scientists can build models to predict disease onset, progression and relapse,” according to UMass Chan Medical School.1 “Information gleaned from the clinical study can also be used to inform the course of other autoimmune diseases in which the body’s immune system attacks its own cells.”

Reference: https://www.umassmed.edu/news/news-archives/2023/06/clinical-study-aims-to-identify-early-molecular-and-biological-signatures-of-vitiligo/

New treatment study in vitiligo.

 

Study Overview

Brief Summary: 

Metformin modulates metabolism in multiple cell types and is currently used to reduce glucose levels and insulin resistance in diabetic patients. The investigators hypothesize that oral metformin can regulate the metabolism of CD8+ T cells, reduce their cytotoxic activity and thus serve as a novel treatment for vitiligo. 

Detailed Description: Metformin modulates metabolism in multiple cell types and is currently used to reduce glucose levels and insulin resistance in diabetic patients. Bae et al. reported that the use of metformin correlated with a lower risk of developing vitiligo, suggesting that metformin could potentially mitigate the disease. The investigators found that treating mouse T cells with metformin during activation reduced their mitochondrial respiration and proliferation, while mice treated with metformin reversed their vitiligo. Therefore, the investigators hypothesize that regulation of CD8+ T cell metabolism in vitiligo patients by metformin will reduce their proliferation and cytotoxic activity, resulting in skin repigmentation and thus serve as a novel treatment. The investigators plan to treat approximately 30 subjects with stable vitiligo. Metformin is FDA-approved for use with dosing from 500-2000 mg/day. It has a rare risk of lactic acidosis, which can be meaningful in patients with risk factors such as renal insufficiency. This risk is directly proportional to the dose given; therefore, participants will be started at a lower dose (500 mg twice daily) with follow-up to monitor any arising symptoms. Per current clinical recommendations, participants will only be increased to higher-dose metformin (1000 mg twice daily) if the initial dose is tolerated. 

Reference: https://www.clinicaltrials.gov/study/NCT05607316?cond=Vitiligo&rank=6

Do you also have high serum gastrin levels? Vitiligo can be caused by the stomach.

I was recently examined by a gastroentrologist for stomach problems and my serum gastrin levels were high. Gastrin stimulates hydrochloric acid when there is no acid in the stomach. Other causes can also increase the gastrin hormone. The research continues. I think you should have your gastrin hormone levels checked. I have added an article below for those who want to look.

Serum Gastrin- Vitiligo: 

https://www.sciencedirect.com/science/article/abs/pii/S0140673674904838?via%3Dihub

Homeopathic Treatment of Vitiligo: A Report of Fourteen Cases

This retrospective study of a series of 14 cases of vitiligo treated with individualized homeopathic compounds showed that although vitiligo is a primary autoimmune disease of the skin, patients with vitiligo may have involvement of multiple systems of the body. This case series showed that prolonged periods of psychological stress might be involved in the onset and progression of the vitiligo. Homeopathic medicine includes a holistic approach to the understanding of the patient and integrates this approach to provide individualized patient treatment . These clinical responses to homeopathic treatment in patients with vitiligo may be considered to be an ideal response to treatment .

However, for an optimal response to homeopathic treatment to occur, treatment should begin when the body has not suffered the effects of the disease for long and before the immune response becomes irreversible. In the 14 cases of vitiligo treated with homeopathy and presented in this case series, the longer the time that elapsed between the onset of vitiligo and the homeopathic consultation, the more difficult it was to obtain a good clinical response. The cases of vitiligo that presented in the advanced stages required more homeopathic remedies and in a correct sequence to see clinical change. An explanation of these findings may have been that the health level of the patients had worsened with time and that the immune system needed more stimulation and time to bring about a positive clinical effect on vitiligo .

In 14 patients with vitiligo treated with individualized homeopathy, the best results were achieved in the patients who were treated in the early stages of their disease.

reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5723025/?fbclid=IwAR1EekDHk_7OXrYm0v42aX-5HLQ5CEUuGpAm4Lr7zt2RuVX8-Q2DIvajROw

World Vitiligo Day

World Vitiligo Day (WVD) 2023 kicks off in Almaty, Kazakhstan, June 23-26, under the theme “Vitiligo: Looking into the Future.” Join our global community for events in Almaty, Brussels, and Atlanta. We'll have vitiligo-focused sessions, microsurgery demos, advocacy endeavors, and inspiring keynotes. Together, we'll create a future free from vitiligo. Stay tuned for more! Find all the details on our website, Events section

Reference: https://www.facebook.com/VRFoundation/posts/pfbid02aQ7x7eBJL277c895wFd8ZDd2booBaKUNEc1N3uRnhkWgj8Ft6rsXGKaXSurYxPpUl?notif_id=1687211457712759&notif_t=notify_me_page&ref=notif

Baricitinib is Effective in Treating Progressing Vitiligo in vivo and in vitro

To evaluate the clinical efficacy and safety of baricitinib, a Janus kinase (JAK) inhibitor, in treating patient with progressing vitiligo, and to further explore the regulation of baricitinib on melanocytes (MCs) in vitro.

Four patients with progressing vitiligo were treated with oral baricitinib for a total of 12 weeks. MCs were cultured in vitro and irradiated by high-dose ultraviolet B (UVB, 150mJ/cm2) to make an MC damaged model (MC-Ds). Baricitinib was added at a final concentration of 25 μM. Dopamine staining and NaOH method were used to measure the tyrosinase activity and melanin level, respectively, real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure the mRNA levels of tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1).

Results

Significant re-pigmentation was observed in the week 12 without obvious side effects. Depigmentation occurred in 2 patients at the 3-month follow-up. Laboratory research found that higher doses of UVB irradiation (150mJ/cm2) could decrease melanin content of MCs, baricitinib (25 μM) could significantly promote tyrosinase activity, melanin content, and TYR, TRP-1 gene expression of MC-Ds.

Conclusion

Our preliminary study showed that baricitinib was effective and safe in treating progressing vitiligo. Baricitinib could promote tyrosinase activity, melanin content and TYR, TRP1 gene expression of MC-Ds in vitro.

Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9160904/

Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a severe autoimmune disease that predominantly affects young women. SLE is characterized by the formation of autoantibodies and immune complex–mediated inflammation and organ damage. Although autoreactive B cells play a key role in the pathogenesis of SLE, B-cell depletion by antibodies has only limited therapeutic efficacy. This paradox has been attributed to the inaccessibility and persistence of autoreactive B cells within lymphatic organs and inflamed tissues or the pathologic role of CD20-negative plasma cells, which may act as an additional source of autoantibodies in patients with SLE. Chimeric antigen receptor (CAR)–modified T cells that have been genetically engineered to recognize CD19 and other B-cell surface antigens have emerged as a powerful tool for the treatment of relapsed or refractory B-cell cancers. This technological breakthrough, together with recent convincing data on the role of B cells in disease pathogenesis derived from preclinical lupus models, provides a rationale for the use of CAR T-cell therapies in patients with SLE.

We report here on the use of autologous CD19 CAR T cells in the treatment of an autoimmune disease. A 20-year-old woman with severe and refractory SLE presented with active lupus nephritis (World Health Organization class IIIA, indicating focal proliferative disease with active lesions), nephrotic syndrome, pericarditis, pleurisy, rash, arthritis, and a history of Libman–Sacks endocarditis. Previous treatments with hydroxychloroquine, high-dose glucocorticoids, cyclophosphamide, mycophenolate mofetil, and tacrolimus, as well as the B-cell–targeting therapies belimumab and rituximab, did not control symptoms, deplete B cells, or abrogate autoimmunity (Fig. S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). All the treatments were stopped before the planned CAR T-cell infusion, and only low-dose prednisolone was administered. CD19 CAR T cells were produced by lentiviral transduction of autologous fresh leukapheresis in the closed automated CliniMACS Prodigy system (Supplementary Methods section in the Supplementary Appendix). After preparatory lymphodepletion with fludarabine at a dose of 25 mg per square meter of body-surface area per day on days −5, −4, and −3 and cyclophosphamide at a dose of 1000 mg per square meter on day −3, an infusion of 1.1×106 CD19 CAR T cells per kilogram of body weight (ratio of CD4+ to CD8+ T cells, 3:1) was administered on day 0.

reference: https://www.nejm.org/doi/full/10.1056/NEJMc2107725

YENİ VİTİLİGO İLACI İÇİN SAĞLIK BAKANLIĞI'NA CİMER'DEN YAZDIK!

Sağlık Bakanlığı tarafından cevaplanması talebi ile

Sayın Yetkili,

Son yıllarda insanlarda görülme sıklığı giderek artan, bağışıklık sistemi hastalığı olarak bilinen ve kişilerde yoğun psikolojik problemler yaratabilen Vitiligo'nun tedavisinde kullanılmak üzere FDA tarafından onaylanan bir ilaç ABD'de piyasaya sürüldü. İlk defa bir topikal krem "vitiligo" tedavisinde kullanılıyor. Şu ana kadar kullanılan tüm tedaviler, başka deri hastalıkları (dermatit, sedef vb.) için üretilen ve kısmen vitiligo için de kullanılan ilaçlardı. ABD'de üretilen bu ilk vitiligo ilacı Sağlık Bakanlığımız tarafından SGK kapsamına alınacak mıdır? Bakanlığımız bu konuda herhangi bir çalışma yürütmekte midir? FDA tarafından onaylanan vitiligo ilacına ait web sitesi aşağıdadır.

https://www.opzelura.com/vitiligo

Bilgilerinizi ve gereğini arz ederim.

Topical methotrexate 1% gel for treatment of vitiligo: A case report and review of the literature

 

          Vitiligo is quite a common hypopigmentary disorder, which may affect both children and adults with important psychological effects due to the well-known leopard skin-like appearance. Even if asymptomatic and not life threatening, vitiligo has to be increasingly studied and treated. Hitherto, the efficacy of topical methotrexate in treatment of vitiligo has not been reported. We herein reporting our preliminary observation on the promising efficacy of topical methotrexate in one patient with stable vitiligo. The patient applied topical methotrexate 1% gel twice daily for 12 weeks. Significant improvement of the lesion with no local or systemic side effects were noted during the course of therapy. We propose that this well-tolerated drug can be used for vitiligo therapy; however, further investigations should be performed to ascertain the exact topically effective dose.

reference:

https://onlinelibrary.wiley.com/doi/full/10.1111/dth.13013

Sağlık Bakanlığı Yeni Vitiligo İlacını Karşılayacak mı?

 

FDA'nın geçtiğimiz günlerde ilk Vitiligo ilacı olan Opzelura (Ruxolitinib) Sağlık bakanlığımız tarafından karşılanacak mı merak konusu. İlacın fiyatı şu an 2 bin dolar ve Türkiye'de bu fiyatı ödeyebilecek hasta sayısı gerçekten sınırlı. Çünkü bu tedavi süreci 24 ila 52 hafta arasında ve %75 repigmentasyon sağlıyor. Sağlık Bakanlığına buradan çağrı yapıyoruz. Lütfen bu ilacı SGK kapsamına alın ve binlerce vitiligo hastasına umut olun!

Where can I buy opzelura?

NOW APPROVED FOR NONSEGMENTAL VITILIGO

IT’S HERE.

THE FIRST AND ONLY
FDA-APPROVED
VITILIGO PRESCRIPTION
TREATMENT THAT HELPS
TO REPIGMENT SKIN.

www.opzelura.com

FDA approves first topical treatment for vitiligo

The U.S. Food and Drug Administration has approved Opzelura (ruxolitinib) as the first topical treatment for vitiligo.

The 1.5 percent cream is approved for continuous topical use twice daily to affected areas of up to 10 percent of body surface area in patients aged 12 years and older. More than 24 weeks of treatment may be needed for satisfactory patient response.

The approval was based on results from the TRuE-V clinical trials, in which more than 600 patients were randomly assigned to Opzelura or placebo. At week 24, 30 percent of patients treated with Opzelura achieved ≥75 percent improvement from baseline in the facial Vitiligo Area Scoring Index (F-VASI75) versus 8 to 13 percent of patients treated with placebo. Approximately half of Opzelura-treated patients achieved F-VASI75 at week 52.

"There have been no FDA-approved therapies available to date and the approval of Opzelura therefore marks a significant milestone," David Rosmarin, M.D., from Tufts Medical Center in Boston, said in a company press release. "I welcome a medical treatment that helps my patients with nonsegmental vitiligo who are interested in potentially reversing the depigmentation caused by their disease."

Approval was granted to Incyte.

Referance:

https://medicalxpress.com/news/2022-07-fda-topical-treatment-vitiligo.html