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Novel rAAV vector mediated intrathecal HGF delivery has an impact on neuroimmune modulation in the ALS motor cortex with TDP-43 pathology.
Genç, Baris; Nho, Boram; Seung, Hana; Helmold, Benjamin; Park, Huiwon; Gözütok, Öge; Kim, Seunghyun; Park, Jinil; Ye, Sanghyun; Lee, Haneul; Lee, Nayeon; Yu, Seung-Shin; Kim, Sunyoung; Lee, Junghun; Özdinler, Hande.
Afiliação
  • Genç B; Department of Neurology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Ave, Chicago, IL, 60611, USA.
  • Nho B; School of Biological Sciences, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.
  • Seung H; Helixmith Co., Ltd., R&D Center, 21, Magokjungang 8-ro 7-gil, Gangseo-gu, Seoul, 07794, Republic of Korea.
  • Helmold B; Helixmith Co., Ltd., R&D Center, 21, Magokjungang 8-ro 7-gil, Gangseo-gu, Seoul, 07794, Republic of Korea.
  • Park H; Department of Neurology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Ave, Chicago, IL, 60611, USA.
  • Gözütok Ö; Helixmith Co., Ltd., R&D Center, 21, Magokjungang 8-ro 7-gil, Gangseo-gu, Seoul, 07794, Republic of Korea.
  • Kim S; Department of Neurology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Ave, Chicago, IL, 60611, USA.
  • Park J; Helixmith Co., Ltd., R&D Center, 21, Magokjungang 8-ro 7-gil, Gangseo-gu, Seoul, 07794, Republic of Korea.
  • Ye S; Helixmith Co., Ltd., R&D Center, 21, Magokjungang 8-ro 7-gil, Gangseo-gu, Seoul, 07794, Republic of Korea.
  • Lee H; Helixmith Co., Ltd., R&D Center, 21, Magokjungang 8-ro 7-gil, Gangseo-gu, Seoul, 07794, Republic of Korea.
  • Lee N; Helixmith Co., Ltd., R&D Center, 21, Magokjungang 8-ro 7-gil, Gangseo-gu, Seoul, 07794, Republic of Korea.
  • Yu SS; School of Biological Sciences, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.
  • Kim S; Helixmith Co., Ltd., R&D Center, 21, Magokjungang 8-ro 7-gil, Gangseo-gu, Seoul, 07794, Republic of Korea.
  • Lee J; School of Biological Sciences, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.
  • Özdinler H; Helixmith Co., Ltd., R&D Center, 21, Magokjungang 8-ro 7-gil, Gangseo-gu, Seoul, 07794, Republic of Korea.
Gene Ther ; 30(7-8): 560-574, 2023 08.
Article em En | MEDLINE | ID: mdl-36823441
Recombinant adeno-associated virus (rAAV)-based gene therapies offer an immense opportunity for rare diseases, such as amyotrophic lateral sclerosis (ALS), which is defined by the loss of the upper and the lower motor neurons. Here, we describe generation, characterization, and utilization of a novel vector system, which enables expression of the active form of hepatocyte growth factor (HGF) under EF-1α promoter with bovine growth hormone (bGH) poly(A) sequence and is effective with intrathecal injections. HGF's role in promoting motor neuron survival had been vastly reported. Therefore, we investigated whether intrathecal delivery of HGF would have an impact on one of the most common pathologies of ALS: the TDP-43 pathology. Increased astrogliosis, microgliosis and progressive upper motor neuron loss are important consequences of ALS in the motor cortex with TDP-43 pathology. We find that cortex can be modulated via intrathecal injection, and that expression of HGF reduces astrogliosis, microgliosis in the motor cortex, and help restore ongoing UMN degeneration. Our findings not only introduce a novel viral vector for the treatment of ALS, but also demonstrate modulation of motor cortex by intrathecal viral delivery, and that HGF treatment is effective in reducing astrogliosis and microgliosis in the motor cortex of ALS with TDP-43 pathology.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Esclerose Lateral Amiotrófica / Córtex Motor Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Esclerose Lateral Amiotrófica / Córtex Motor Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article