Reductions in oculogyric crisis duration and frequency in children with aromatic L-amino acid decarboxylase deficiency treated with eladocagene exuparvovec: results from 3 clinical trials
Paul Wuh-Liang Hwu, Yin-Hsiu Chien, Ni-Chung Lee, Sheng-Hong Tseng, Antonio Wang, Allan Kristensen, Panayiota Trifillis, Tuna Koca, Chun-Hwei Tai
Objectives: Aromatic L-Amino Acid Decarboxylase (AADC) deficiency is a rare autosomal recessive disorder resulting in marked dopamine loss, impeding normal motor development. Oculogyric crises (OGC) are involuntary eye movements characteristic of AADC deficiency, which are linked to decreased dopamine levels. OGCs can be accompanied by limb stiffness, torso rigidity, and autonomic signs. Eladocagene exuparvovec, a recombinant adeno-associated viral vector containing the human cDNA encoding the AADC enzyme, was studied in 3 AADC clinical trials.
Methods: Eladocagene exuparvovec was administered as a bilateral infusion in the putamen of 28 children with AADC deficiency in 3 trials (AADC-CU/1601 [8 patients, completed], AADC-010 [10 patients, completed], and AADC-011 [10 patients to date; ongoing]). Patients received a total of 1.8 × 10^11 vg (n=21) or 2.4 × 10^11 vg (n=7; AADC-011)]. Duration (h/wk) and frequency (episodes/wk) of OGC episodes were calculated at baseline and 3 to 12 months after treatment.
Results:. At baseline, mean duration of OGC episodes was 12.58 h/wk (n=22). OGC was reduced from baseline by a mean of 2.08 h/wk at 3 months (n=20), 2.24 h/wk at 6 months (n=12), 3.2h/wk at 9 months (n=12), and 3.64 h/wk at 12 months (n=8). At baseline, mean frequency of OGC was 2.63 episodes/wk (n=22). By month 3, the mean frequency decreased to 1.93 episodes/wk (n=20), by month 6, it was 1.9 episodes/wk (n=12), and remained at ~2 episodes/wk from months 9 to 12.
Conclusions: These results indicate a pattern of steady and sustained decrease over time in OGC episodes after PTC-AADC gene therapy.
Keywords: Rare Diseases, AADC Deficiency, Gene Therapy, Movement Disorders
Paul Wuh-Liang Hwu
National Taiwan University Hospital and National Taiwan University College of Medicine
Taiwan
Yin-Hsiu Chien
National Taiwan University Hospital and National Taiwan University College of Medicine
Taiwan
Ni-Chung Lee
National Taiwan University Hospital and National Taiwan University College of Medicine
Taiwan
Sheng-Hong Tseng
National Taiwan University Hospital and National Taiwan University College of Medicine
Taiwan
Antonio Wang
PTC Therapeutics, Inc.
United States
Allan Kristensen
PTC Therapeutics, Inc.
United States
Panayiota Trifillis
PTC Therapeutics, Inc.
United States
Tuna Koca
PTC Therapeutics, Inc.
Switzerland
Chun-Hwei Tai
National Taiwan University Hospital and National Taiwan University College of Medicine
Taiwan
Objectives: Aromatic L-Amino Acid Decarboxylase (AADC) deficiency is a rare autosomal recessive disorder resulting in marked dopamine loss, impeding normal motor development. Oculogyric crises (OGC) are involuntary eye movements characteristic of AADC deficiency, which are linked to decreased dopamine levels. OGCs can be accompanied by limb stiffness, torso rigidity, and autonomic signs. Eladocagene exuparvovec, a recombinant adeno-associated viral vector containing the human cDNA encoding the AADC enzyme, was studied in 3 AADC clinical trials.
Methods: Eladocagene exuparvovec was administered as a bilateral infusion in the putamen of 28 children with AADC deficiency in 3 trials (AADC-CU/1601 [8 patients, completed], AADC-010 [10 patients, completed], and AADC-011 [10 patients to date; ongoing]). Patients received a total of 1.8 × 10^11 vg (n=21) or 2.4 × 10^11 vg (n=7; AADC-011)]. Duration (h/wk) and frequency (episodes/wk) of OGC episodes were calculated at baseline and 3 to 12 months after treatment.
Results:. At baseline, mean duration of OGC episodes was 12.58 h/wk (n=22). OGC was reduced from baseline by a mean of 2.08 h/wk at 3 months (n=20), 2.24 h/wk at 6 months (n=12), 3.2h/wk at 9 months (n=12), and 3.64 h/wk at 12 months (n=8). At baseline, mean frequency of OGC was 2.63 episodes/wk (n=22). By month 3, the mean frequency decreased to 1.93 episodes/wk (n=20), by month 6, it was 1.9 episodes/wk (n=12), and remained at ~2 episodes/wk from months 9 to 12.
Conclusions: These results indicate a pattern of steady and sustained decrease over time in OGC episodes after PTC-AADC gene therapy.
Keywords: Rare Diseases, AADC Deficiency, Gene Therapy, Movement Disorders
Paul Wuh-Liang Hwu
National Taiwan University Hospital and National Taiwan University College of Medicine
Taiwan
Yin-Hsiu Chien
National Taiwan University Hospital and National Taiwan University College of Medicine
Taiwan
Ni-Chung Lee
National Taiwan University Hospital and National Taiwan University College of Medicine
Taiwan
Sheng-Hong Tseng
National Taiwan University Hospital and National Taiwan University College of Medicine
Taiwan
Antonio Wang
PTC Therapeutics, Inc.
United States
Allan Kristensen
PTC Therapeutics, Inc.
United States
Panayiota Trifillis
PTC Therapeutics, Inc.
United States
Tuna Koca
PTC Therapeutics, Inc.
Switzerland
Chun-Hwei Tai
National Taiwan University Hospital and National Taiwan University College of Medicine
Taiwan
Tuna Koca
PTC Therapeutics, Inc. Switzerland
PTC Therapeutics, Inc. Switzerland