echemi logo
Product
  • Product
  • Supplier
  • Inquiry
    Home > Biochemistry News > Biotechnology News > Persistence and Rescue: The Birth of China's First Approved RNA Therapy

    Persistence and Rescue: The Birth of China's First Approved RNA Therapy

    • Last Update: 2021-09-20
    • Source: Internet
    • Author: User
    Search more information of high quality chemicals, good prices and reliable suppliers, visit www.echemi.com

    Article source: Medical Rubik's Cube Pro

    Author: Li Yuan

    On February 28, 2019, the National Medical Products Administration (NMPA) formally approved the marketing of Nosinassan Sodium (active ingredient: Nosinasana)
    .


    This is an antisense oligonucleotide (ASO) therapy jointly developed by Biogen and Ionis Pharmaceuticals for the treatment of spinal muscular atrophy (SMA).


    Spinal muscular atrophy is an autosomal recessive genetic disease, also known as progressive muscular atrophy
    .


    Patients are divided into type 1 (infant type), type 2 (intermediate type), type 3 (adolescent type) and type 4 (adult type) according to their age of onset and severity of disease.


    Due to the lack of awareness of premarital examinations and pregnancy examinations among the population or the limitations of detection technology, most children only know that they have the disease after they develop symptoms
    .


    In type 1 spinal muscular atrophy, the average life expectancy of children is less than two years


    In China, Noxinagen sodium is the first drug approved for the treatment of spinal muscular atrophy.
    Although it is expensive, it brings hope to parents who are waiting in the dark
    .

    "At least my child is saved
    .


    "

    The birth of Nocinnat is actually a story that promotes a defective gene to save another mutant gene
    .


    The pair of "difficult brothers" are named SMN1 and SMN2, which are motor neuron survival genotypes 1 and 2


    In patients with spinal muscular atrophy, the mutation of SMN1 reduces the expression of SMN protein, the motor neurons in the spinal cord and brainstem degenerate, and the muscles gradually become weak and atrophy
    .

    SMN2 is the "brother" of SMN1.
    Although SMN2 is almost identical to SMN1 and encodes the same SMN protein, it is a defective gene.
    Most of the precursor mRNA of SMN2 will be abnormally spliced ​​and translated into short and unstable The peptide does not produce stable and sufficient SMN protein
    .


    Therefore, if you want to replace the mutant SMN1 with SMN2, you need to repair the defects of SMN2


    The team of Dr.
    Adrian Krainer of Cold Spring Harbor Laboratory has been studying a splicing activator SRSF1 since the 1980s.
    They found that when the RNA information of SMN2 is spliced, the expression of SRSF1 is lost, which causes exon 7 to be skipped.
    , The lack of key information makes SMN2 unable to express the normal amount of SMN protein
    .

    Source: ThermoFisher

    The key to the defect has been found, and the next step is to fix this defect
    .

    In 2004, Dr.
    Krainer’s team and Ionis researchers began to collaborate to design drugs to correct the skipping of exon 7.
    Sub 7 is included to form a full-length SMN2 transcript, which will produce a full-length functional SMN protein after translation
    .

    Source: Nature

    Since then, this ASO drug has been continuously optimized and its efficacy has been proven
    .


    In mouse experiments, ASO can correct the major defects of SMN2 in living cells and reverse the symptoms of type 1 spinal muscular atrophy


    In December 2016, only 3 months after the submission of the New Drug Application (NDA), the US Food and Drug Administration (FDA) approved the marketing of Nosinassan (trade name: Spinraza), and Nossinasana became the world's number one.
    A drug for the treatment of myelogenous muscular atrophy
    .

    Since then, Nosinathan has been approved by the European Medicines Agency (EMA), the Japanese Medicines and Medical Devices Agency (PMDA) and NMPA.
    Now patients with spinal muscular atrophy in more than 50 countries and regions around the world can use this drug Get treatment
    .


    Scientists' tireless pursuit and exploration for decades has rekindled hope in the lives of such patients


    Note: The generic name of nusinersen listed in China is nusinersen and nusinersen abroad


    Reference materials:

    [1] The world's first spinal muscular atrophy treatment drug Noxinassen Sodium Injection was officially launched in China (Source: PR Newswire)

    [2] Killer Disease, Miracle Drug (Source: Cold Spring Harbor Laboratory)

    [3] Hua, Y.
    , Sahashi, K.
    , Rigo, F.
    , et al.
    Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model.
    Nature (2011)

    [4] Milestones in antisense RNA research (Source: Nature)

    [5] Roberts, TC, Langer, R.
    & Wood, MJA Advances in oligonucleotide drug delivery.
    Nat Rev Drug Discov (2020)

    This article is an English version of an article which is originally in the Chinese language on echemi.com and is provided for information purposes only. This website makes no representation or warranty of any kind, either expressed or implied, as to the accuracy, completeness ownership or reliability of the article or any translations thereof. If you have any concerns or complaints relating to the article, please send an email, providing a detailed description of the concern or complaint, to service@echemi.com. A staff member will contact you within 5 working days. Once verified, infringing content will be removed immediately.

    Contact Us

    The source of this page with content of products and services is from Internet, which doesn't represent ECHEMI's opinion. If you have any queries, please write to service@echemi.com. It will be replied within 5 days.

    Moreover, if you find any instances of plagiarism from the page, please send email to service@echemi.com with relevant evidence.