Bringing CNS Members Together to Make Children’s Lives Better


Gene Therapy Clinical Trial for GM2 Gangliosidosis

Phase 1/2, Open-Label Clinical Trial to Evaluate the Safety and Efficacy of TSHA-101, an Intrathecally Dosed Gene Therapy for Treatment of Infantile Onset GM2 Gangliosidosis

Dear Doctor,
The Queen’s University Phase 1/2 gene therapy trial for infants suffering from GM2 gangliosidosis is now enrolling patients globally in Kingston, Ontario, Canada.

GM2 gangliosidosis, also known as Tay-Sachs (TSD) or Sandhoff disease (SD), is a rare and fatal pediatric neurodegenerative lysosomal storage genetic disorder caused by defects in the HEXA (leading to Tay-Sachs disease) or HEXB (leading to Sandhoff disease) genes that encode the two subunits of the .-hexosaminidase A (HexA) enzyme. According to the onset and rate of disease progression, the condition can be categorized in infantile, juvenile, and adult forms. There are no current treatments for GM2 gangliosidosis.

This clinical trial will be a first-in-human Phase 1/2 open-label study using TSHA-101. TSHA-101 uses a recombinant viral vector called adeno-associated virus, serotype 9 (AAV9), to deliver genetic material intrathecally to the central nervous system, including the brain and spinal cord, for the treatment of infantile GM2 gangliosidosis. The protein product of the viral vector will be both the .-and .-subunits, making this therapy suitable for both the TSD and SD populations.

The primary objective of the trial is to assess the safety and tolerability of a one-time intrathecal administration of TSHA-101 in subjects up to 12 months of age with a confirmed diagnosis of GM2 gangliosidosis. The secondary objective is to demonstrate preliminary efficacy of intrathecally delivered TSHA-101 at the selected dose. Measures of preliminary efficacy include neurodevelopmental, motor and biomarker assessments.

For additional information about the trial, please click here.

For information about enrolling patients, please contact the Principal Investigator, Dr. Anupam Sehgal, at:


  1. Efficacy of a Bicistronic Vector for Correction of Sandhoff Disease in a Mouse Model. Woodley E, Osmon KJL, Thompson P, Richmond C, Chen Z, Gray SJ, Walia JS. Mol Ther Methods Clin Dev. 2018 Oct 26;12:47-57.
  2. Novel Vector Design and Hexosaminidase Variant Enabling Self-Complementary Adeno-Associated Virus for the Treatment of Tay-Sachs Disease. Karumuthil-Melethil S, Nagabhushan Kalburgi S, Thompson P, Tropak M, Kaytor MD, Keimel JG, Mark BL, Mahuran D, Walia JS, Gray SJ. Hum Gene Ther. 2016 Jul;27(7):509-21.
  3. Systemic Gene Transfer of a Hexosaminidase Variant Using an scAAV9.47 Vector Corrects GM2 Gangliosidosis in Sandhoff Mice. Osmon KJ, Woodley E, Thompson P, Ong K, Karumuthil-Melethil S, Keimel JG, Mark BL, Mahuran D, Gray SJ, Walia JS. Hum Gene Ther. 2016 Jul;27(7):497-508.
  4. Long-term correction of Sandhoff disease following intravenous delivery of rAAV9 to mouse neonates. Walia JS, Altaleb N, Bello A, Kruck C, LaFave MC, Varshney GK, Burgess SM, Chowdhury B, Hurlbut D, Hemming R, Kobinger GP, Triggs-Raine B. Mol Ther. 2015 Mar;23(3):414-22.
  5. GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies. Leal AF, Benincore-Flórez E, Solano-Galarza D, Garzón Jaramillo RG, Echeverri-Peña OY, Suarez DA, Alméciga-Díaz CJ, Espejo-Mojica AJ. Int J Mol Sci. 2020 Aug 27;21(17):6213.
  6. Genetics and Therapies for GM2 Gangliosidosis. Cachon-Gonzalez MB, Zaccariotto E, Cox TM. Curr Gene Ther. 2018;18(2):68-89.

PLEASE NOTE: This email was sent to CNS members with the approval and cooperation of the Child Neurology Society. A fee was paid to the Child Neurology Society for providing this email service. Official notice is hereby given that the CNS does not officially endorse the product, service, research/study, position, event or company/institution referenced, nor is any implication of endorsement intended by the contracting party. The CNS never releases member email addresses. Members may decide individually to provide their own email to third parties but are strictly prohibited from providing any member emails other than their own for any reason.