Neonatal screening for spinal muscular atrophy by measuring SMN protein in dried blood spots

• Project/Area Number: 20K08259
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kumamoto University
• Principal Investigator: Nakamura Kimitoshi 熊本大学, 大学院生命科学研究部(医), 教授 (30336234)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 新生児スクリーニング / SMN蛋白 / qPCR / 脊髄性筋萎縮症 / ELISA法

Outline of Research at the Start

脊髄性筋萎縮症(SMA)は筋萎縮と進行性筋力低下を呈し、重症例は1歳までに死に至る。核酸薬による治療や遺伝子治療薬の開発も進んでおり、生後早期にこれらの治療をおこなうと、歩行が可能なまでに発達できることが分かってきた。SMAではqPCR法を用いた新生児スクリーニング法が開発されているが、遺伝子診断を用いたスクリーニングであるため、倫理的な課題は多い。われわれは、新生児スクリーニング用の濾紙血を用いて、SMN蛋白を測定する方法を開発した（特許出願準備中）。従来のqPCR法によって生じる倫理的な課題を解決し、新生児期のSMAのスクリーニングを可能にしSMAの疾患概要を明らかにする。

Outline of Final Research Achievements

Spinal muscular atrophy (SMA) is a disease that presents with muscle atrophy and progressive muscle weakness due to degeneration of the anterior horn cells of the spinal cord. became. For SMA, a newborn screening method using qPCR has been developed, but there are many ethical issues because it is screening using genetic diagnosis. We have developed a method to measure SMN protein using filter paper blood for neonatal screening. Then, neonatal SMA was screened by measuring SMN protein using filter paper blood samples. This test actually identified SMA patients during newborn screening and allowed gene therapy to be used as an early treatment.

Academic Significance and Societal Importance of the Research Achievements

脊髄性筋萎縮症(SMA)は、遺伝子治療薬の開発も進んでおり、生後早期に治療をおこなうと、歩行が可能なまでに発達できることが分かってきた。このSMAでは、qPCR法を用いた新生児スクリーニング法が開発されているが、遺伝子診断を用いたスクリーニングであるため、倫理的な課題は多く、産科施設で説明をおこなってスクリーニングをおこなうには解決すべき点が多い。本研究によって本症の早期診断と新生児期のスクリーニングを可能にし、適切な治療時期の検討を行うことで、SMAの早期診断と治療の意義を明らかにすることができた。

Research Products

• [Journal Article] Clinical manifestation and long-term outcome of citrin deficiency: Report from a nationwide study in Japan (2022)
  • Author(s): Kido J, Haberle J, Sugawara K, Tanaka T, Nagao M, Sawada T, Wada Y, Numakura C, Murayama K, Watanabe Y, Kojima-Ishii K, Sasai H, Kosugiyama K, Nakamura K.
  • Journal Title: J Inherit Metab Dis . Volume: none Issue: 3 Pages: 431-444
  • DOI: 10.1002/jimd.12483
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Newborn screening for Gaucher disease in Japan. (2022)
  • Author(s): Sawada T, Kido J, Sugawara K, Yoshida S, Matsumoto S, Shimazu T, Matsushita Y, Inoue T, Hirose S, Endo F, Nakamura K.
  • Journal Title: Mol Genet Metab Rep. Volume: 31 Pages: 100850-100850
  • DOI: 10.1016/j.ymgmr.2022.100850
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Circulating extracellular vesicle microRNAs associated with adverse reactions, proinflammatory cytokine, and antibody production after COVID-19 vaccination. (2022)
  • Author(s): Miyashita Y, Yoshida T, Takagi Y, Tsukamoto H, Takashima K, Kouwaki T, Makino K, Fukushima S, Nakamura K, Oshiumi H.
  • Journal Title: NPJ Vaccines Volume: 7 Issue: 1 Pages: 16-16
  • DOI: 10.1038/s41541-022-00439-3
  • Peer Reviewed / Open Access
• [Journal Article] Newborn screening for spinal muscular atrophy in Japan: One year of experience. (2022)
  • Author(s): Sawada T, Kido J, Sugawara K, Yoshida S, Ozasa S, Nomura K, Okada K, Fujiyama N, Nakamura K.
  • Journal Title: Newborn screening for spinal muscular atrophy in Japan: One year of experience. Volume: 32 Pages: 100908-100908
  • DOI: 10.1016/j.ymgmr.2022.100908
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Muscle biochemical and pathological diagnosis in Pompe disease (2022)
  • Author(s): Saito Yoshihiko、Nakamura Kimitoshi、Fukuda Tokiko、Sugie Hideo、Hayashi Shinichiro、Noguchi Satoru、Nishino Ichizo
  • Journal Title: Journal of Neurology, Neurosurgery and Psychiatry Volume: 93 Issue: 11 Pages: 1142-1145
  • DOI: 10.1136/jnnp-2022-329085
  • Peer Reviewed
• [Journal Article] Pathogenic variants of ornithine transcarbamylase deficiency: Nation-wide study in Japan and literature review. (2022)
  • Author(s): Kido J, Sugawara K, Sawada T, Matsumoto S, Nakamura K.
  • Journal Title: Front Genet. Volume: 13 Pages: 952467-952467
  • DOI: 10.3389/fgene.2022.952467
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Severe metabolic acidosis with cardiac involvement in DNM1L-related mitochondrial encephalopathy. (2022)
  • Author(s): Kinoshita Y, Momosaki K, Matsumoto S, Murayama K, Nakamura K
  • Journal Title: Pediatr Int. Volume: 64(1) Issue: 1
  • DOI: 10.1111/ped.14879
  • Peer Reviewed
• [Journal Article] Characteristics of Neurological Symptoms in Adult Japanese Patients with Fabry Disease (2021)
  • Author(s): Sawada Jun、Nakagawa Naoki、Kano Kohei、Saito Tsukasa、Katayama Takayuki、Sawada Takaaki、Momosaki Ken、Nakamura Kimitoshi、Hasebe Naoyuki
  • Journal Title: Internal Medicine Volume: 60 Issue: 12 Pages: 1819-1826
  • DOI: 10.2169/internalmedicine.6420-20
  • NAID: 130008052662
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2021-06-15
  • Peer Reviewed / Open Access
• [Journal Article] The Predictive Value of Procalcitonin and High-Sensitivity C-Reactive Protein for Early Bacterial Infections in Preterm Neonates. (2021)
  • Author(s): Naramura T, Imamura H, Yoshimatsu H, Hirashima K, Irie S, Inoue T, Tanaka K, Mitsubuchi H, Nakamura K, Iwai M
  • Journal Title: Neonatology Volume: 118(1) Issue: 1 Pages: 28-36
  • DOI: 10.1159/000512523
  • Peer Reviewed
• [Journal Article] Hyperprolinemia type I caused by homozygous p.T466M mutation in PRODH. (2021)
  • Author(s): Hama R, Kido J, Sugawara K, Nakamura T, Nakamura K
  • Journal Title: Hum Genome Volume: 8(1) Issue: 1
  • DOI: 10.1038/s41439-021-00159-5
  • Peer Reviewed / Open Access
• [Journal Article] Current status of newborn screening for Pompe disease in Japan. (2021)
  • Author(s): Sawada T, Kido J*, Sugawara K, Momosaki K, Yoshida S, Kojima-Ishii K, Inoue T, Matsumoto S, Endo F, Ohga S, Hirose S, Nakamura K.
  • Journal Title: Orphanet J Rare Dis. Volume: 18 Issue: 1 Pages: 516-516
  • DOI: 10.1186/s13023-021-02146-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Newborn Screening for Pompe Disease (2020)
  • Author(s): Sawada Takaaki、Kido Jun、Nakamura Kimitoshi
  • Journal Title: International Journal of Neonatal Screening Volume: 6 Issue: 2 Pages: 31-31
  • DOI: 10.3390/ijns6020031
  • Peer Reviewed
• [Journal Article] Role of induced pluripotent stem cells in lysosomal storage diseases. (2020)
  • Author(s): Kido J, Nakamura K, Era T.
  • Journal Title: Mol Cell Neurosci. Volume: 108 Pages: 103540-103540
  • DOI: 10.1016/j.mcn.2020.103540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Detection of novel Fabry disease-associated pathogenic variants in Japanese patients by newborn and high-risk screening. (2020)
  • Author(s): Sawada T, Kido J, Sugawara K, Matsumoto S, Takada F, Tsuboi K, Ohtake A, Endo F, Nakamura K.
  • Journal Title: Mol Genet Genomic Med. Volume: 11 Issue: 11
  • DOI: 10.1002/mgg3.1502
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fabry disease screening in high-risk populations in Japan: a nationwide study. (2020)
  • Author(s): Yoshida S, Kido J, Sawada T, Momosaki K, Sugawara K, Matsumoto S, Endo F, Nakamura K.
  • Journal Title: Orphanet J Rare Dis. Volume: 15 Issue: 1 Pages: 220-220
  • DOI: 10.1186/s13023-020-01494-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pharmacokinetics and pharmacodynamics of JR-051, a biosimilar of agalsidase beta, in healthy adults and patients with Fabry disease: Phase I and II/III clinical studies (2020)
  • Author(s): Nakamura Kimitoshi、Kawashima Satoshi、Tozawa Hirotaka、Yamaoka Mariko、Yamamoto Tatsuyoshi、Tanaka Noboru、Yamamoto Ryuji、Okuyama Torayuki、Eto Yoshikatsu
  • Journal Title: Molecular Genetics and Metabolism Volume: 130 Issue: 3 Pages: 215-224
  • DOI: 10.1016/j.ymgme.2020.04.003
  • Peer Reviewed
• [Journal Article] Newborn screening for Fabry disease in the western region of Japan. (2020)
  • Author(s): Sawada T, Kido J, Yoshida S, Sugawara K, Momosaki K, Inoue T, Tajima G, Sawada H, Mastumoto S, Endo F, Hirose S, Nakamura K.
  • Journal Title: Mol Genet Metab Rep. Volume: 22 Pages: 100562-100562
  • DOI: 10.1016/j.ymgmr.2019.100562
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 熊本地域における新生児SCID pilot スクリーニングの経過報告 (2020)
  • Author(s): 吉田真一郎1) 、山内芳裕1)、水上智之2)、遠藤文夫3)、中村公俊4)
  • Organizer: 第47回日本マススクリーニング学会学術集会
• [Presentation] 乾燥ろ紙血を用いたいたライソゾーム病スクリーニング陽性症例とその臨床像 (2020)
  • Author(s): 松本志郎1, 澤田貴彰1, 百崎謙2, 三渕浩3, 遠藤文夫4, 中村公俊1
  • Organizer: 第47回日本マススクリーニング学会学術集会