Tailored gene therapy has emerged! or will bring a new era of personalized medicine

Although Mila was pronounced dead to be 12 years old after her arrest, Mila's parents did not give up hopeThey set up the Mila's Miracle Foundation to raise money for people with Beaton's, like MilaAt this point, when we saw Mila's parents' perseverance, DrTimothy Yu, a professor of neurology at Boston Children's Hospital who specializes in pediatric genetics, reached out to help and offered to personalize the treatment for MilaASHG2018 tells the story of Mira's healing
at the 2018 annual meeting of the American Society for Human Genetics, DrYu brought the latest treatment for MilaFirst, he and his team sequenced Mira's genome in detail, and found that the cause of Mira's illness was the insertion of a fragment called a transcribed transposon in a gene that expressed important proteases (CLN7), which prevented the normal expression of the geneThis particular genetic defect is not suitable for the only rare disease drug approved by the FDA at the time because of its indications are type 2 Betten's disease (CLN2)What can be done to restore the normal expression of the CLN7 gene?On December 23, 2016, a treatment called Spinraza was approved by the FDA, the first approved antisense oligotide, ASO therapyIt is a specially designed piece of DNA that, by binding to RNA, can alter the RNA's splicing process and restore normal protein expression to genes that were previously unable to produce normal proteinsand that's the treatment Mila needs!less than a year! "Milasen" new drug was successfully developed
since the treatment has been determined, it is fast horse whipping to develop drugs! "Saving Mira" became the rallying cry, Yu and the research team invited senior genetic experts, toxicologists, can quickly produce molecular drugs companies ..At least 30 scientists and doctors are involved in the development of new drugsThe timeline developed by Milasen was developed in just eight months, and a new molecular drug, "milasen", designed specifically for Mila's CLN7 mutant gene based on ASO therapy, was designed to work in its cells to synthesize useful proteins January 2018, the FDA approved the drug for patient trials Since then, Mila's treatment has officially begun! during the treatment, Yu and his team chose to inject drugs into their spinal fluid, which enters the brain and repairs neurons After a few months of medication, Mila gradually improved Most thankfully, her seizures dropped sharply, from 20 or 30 times a day, lasting two minutes at a time, to 5-12 seizures a day, reducing her duration to a few seconds This battle, win! October 2018, Mila was discharged from the hospital and returned home, and although she was still invisible, unable to speak and with reduced mobility, her physical function improved dramatically Since then, we can say that this battle, won! asks the three-time personalization of the era of drug regulation where to go? people eat grain grain to produce a hundred diseases, which is a saying that has been circulating in China for a long time, but also side shows that everyone in the world is suffering from different diseases, but also for rare diseases such as Mira, the world may only have a few or a dozen of the same cases Therefore, the development of innovative therapies may be the only option for rare patients, or a good start for personalized treatment in the future But on October 9th, shortly after the publication of the Milasen-related paper in the New England Journal of Medicine, the journal published an editorial co-signed by Dr Janet Woodcock, director of the FDA's Center for Drug Assessment and Research, and Peter Marks, director of the Center for Biological Products Assessment and Research (CBER) DOI: 10.1056/NEJMoa1813279 article begins by pointing out that with the rapid development of genomics and the rise of independent laboratories, the rapid response of third-party pharmaceutical companies has made "personalized and customized drugs" no longer a dream But "personalized" drug development poses new challenges for regulators, such as: What evidence is needed to use the drug in the human body? What is the minimum guarantee of security? How do I choose a dose and develop a treatment plan? After taking the drug, when the patient is in critical condition, how to choose? How is the effectiveness of treatment assessed? second, when patients are involved in personalized and customized drugs, the process of drug development is disrupted Instead of finding patients for clinical trials after drug development is completed, patients are first introduced to the trial and then developed When patients crave the opportunity to "live" at all costs, how do doctors stop? third, and while everyone is immersed in the joy of Mira's healing, the huge cost behind it is only known to doctors and family members Who will pay for the "bill" of personalized medical care in the future? And who would want to be on the market for these "personally usable" drugs? 2020, the FDA will soon introduce the "personalized drug" research and management principles, perhaps by then these questions will be a perfect answer Let's wait and see! references: Patient-Customized Oligonucleo Therapy for a Rare Genetic Disease 2 Drug Regulation in The Era of The Arif I, Her Name Is Mila.