Treatment of Myasthenic Syndrome due to Choline Acetyltransferase Deficiency Using AAV9-mediated Gene Therapy

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Grant Award Details

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Grant Application Details

Application Title:

Treatment of Myasthenic Syndrome due to Choline Acetyltransferase Deficiency Using AAV9-mediated Gene Therapy

Public Abstract:
Research Objective

Use of a viral vector to transport a normal gene to children with severe motor and respiratory disabilities caused by an inborn defect of the choline acetyltransferase (ChAT) gene.


Treatment of an incurable disease in infants and potential amelioration of symptoms of neuro degenerative diseases with deficient cholinergic system such as Alzheimer and Parkinson disease.

Major Proposed Activities

  • Refining the development of an AAV vector carrying the human ChAT gene and transducing normal human induced pluripotent stem cells (iPSCs) with this vector to demonstrate effective transduction.
  • Transducing iPSCs cells derived from affected patients and demonstrating recovery of normal ChAT function by an enzymatic potency assay.
  • Injection of the AAV virus transporting the human ChAT gene into mice that are deficient of this gene and testing the survival and motor strength of injected and non-injected mice
  • Immunohistochemistry to measure the expression of choline acetyltransferase in the central nervous system of AAV-treated and non-treated mice.
  • Quantitation of vector copies and RNA expression of the ChAT gene in the nervous system and peripheral organs using real time PCR.
  • Histologic analysis of brain and peripheral tissues of long-surviving mice injected with the AAV vector to verify the absence of long term adverse effects.
Statement of Benefit to California:
• Deficiency of ChAT affects all racial groups but is common in Native American and Asians which are two important ethnic groups of the State of California. • Current treatments for deficiency of choline acetyltransferase are ineffective and the ancillary services (care of tracheotomy, mechanical ventilation, and gastric tubes) are very onerous for the State of California. • The development of this novel gene therapy locally will provide jobs and financial growth for the State of California.