July 2023: Evidence from a small-scale clinical trial shows that myasthenia gravis, an autoimmune disorder of the nervous system, could be treated with a variation of CAR-T, an advanced blood cancer immunotherapy. The modified CAR-T treatment, which stands for chimeric antigen receptor T-cell, was used by scientists. It could reduce myasthenia gravis symptoms for a longer time and didn’t cause any major side effects. The study, which was published in The Lancet Neurology, was paid for by a small business grant from the National Institute of Neurological Disorders and Stroke (NINDS), which is part of the National Institutes of Health. The grant was given to Gaithersburg, Maryland-based company Cartesian Therapeutics.
Using a groundbreaking therapy like CAR-T to potentially treat a neurological disorder shows how flexible immunoterapiya can be when there are few or no other treatment options,” said Emily Caporello, Ph.D., head of the NINDS Small Business Programme.
Myasthenia gravis uzoq muddatli otoimmün kasallik bo'lib, u tananing immun tizimi asab hujayralari mushaklar bilan gaplashadigan oqsilga hujum qilganda sodir bo'ladi. Kasallik mushaklarning kuchsizligi bilan tavsiflanadi, u odam faol bo'lganida kuchayadi va ba'zida odam dam olganda yaxshilanadi. Bizda mavjud bo'lgan muolajalarning asosiy maqsadi simptomlarni, ayniqsa mushaklar kuchsizligini kamaytirishdir.
Tadqiqotda umumiy miyasteniya gravisli 14 kishiga turli miqdorda Dekart-08 berildi, bu miyasteniya gravisini keltirib chiqaradigan antikorlarni hosil qiluvchi hujayralarga qaratilgan CAR-T terapiyasining o'zgartirilgan shakli. Eng yaxshi doz olti hafta davomida haftada bir marta bitta tabletka ekanligi aniqlandi. Davolashning qanchalik yaxshi ishlashi haqidagi dastlabki ma'lumotlar rag'batlantiradi, ammo uning qanchalik yaxshi ishlashini aniqlash uchun ko'proq klinik testlar talab qilinadi. Dekart-08 ni qabul qilgan uchta odamda barcha yoki deyarli barcha alomatlar yo'qolgan. Ushbu ta'sirlar davolanishdan keyin olti oy davom etdi. Yana ikkitasi og'ir MG bilan og'rigan ba'zi odamlarga vena ichiga yuboriladigan immunoglobulin bilan davolanishga muhtoj emas edi.
Murat V. Kalayoglu, MD, Ph.D, Cartesian Therapeutics kompaniyasi prezidenti va bosh direktori, "Biz davolashdan keyin kamida olti oy davom etgan Decartes-08ga chuqur, uzoq davom etadigan javoblarni ko'rdik" dedi. "Biz endi kattaroq randomizatsiyalangan, platsebo-nazorat ostidagi tadqiqotni boshladik, bu muhandislik asrab oluvchi hujayra terapiyasi uchun birinchi turdagi."
In CAR-T therapy, a patient’s T-cells are reprogrammed to fight a specific target. T-cells are a key part of the immune system that can find and kill invading pathogens. With qon saratoni, the cancer itself is now the new target. For myasthenia gravis, the goal is to kill the bad cells that make the antibodies that cause damage.
Ko'pgina immunoterapiyalar, shu jumladan CAR-T, katta nojo'ya ta'sirlarni keltirib chiqarishi mumkin, ular rivojlangan saraton holatlarida bardoshli bo'lsa-da, miyasteniya gravis va boshqa uzoq muddatli sharoitlarda foydalanishni imkonsiz qiladi. T-hujayralari odatda DNK tomonidan o'zgartiriladi, u hujayrada qoladi va hujayra bo'linganda har safar nusxalanadi. Bu harakatni kuchaytirishi va xavfli yon ta'sirga olib kelishi mumkin.
Dekart-08 T-hujayralarni o'zgartirish uchun DNKdan foydalanmaydi, chunki hujayralar bo'linganda DNK o'zini nusxalaydi. Buning o'rniga u hujayralar bo'linganda o'zini ko'paytirmaydigan messenjer RNK (mRNK) dan foydalanadi. Natijada bitta doza o'rniga bir martadan ko'proq beriladigan qisqa davolash davri bo'lib, DNK-dasturlashtirilgan CAR-T terapiyasi odatda shunday ishlaydi. Ushbu tadqiqotning asosiy maqsadi Dekart-08 ning to'g'ri dozasini topish va iloji boricha kamroq yon ta'sirga olib keladigan mushaklar kuchsizligi alomatlarini kamaytirish edi.
In a larger klinik tadqiqotlar, Descartes-08 therapy is now being tried to see if it can help reduce the symptoms of myasthenia gravis. Importantly, there will also be a placebo group in this study. This is an important control to make sure that any improvement seen is due to the treatment and not something else.
