Gene therapy with eladocagene exuparvovec improves cognition and language in patients with aromatic L-amino acid decarboxylase deficiency
Paul Wuh-Liang Hwu, Yin-Hsiu Chien, Ni-Chung Lee, Sheng-Hong Tseng, Antonia Wang, Panayiota Trifillis, Tuna Koca, Chun-Hwei Tai
Objectives: Aromatic L-amino acid decarboxylase (AADC) deficiency is caused by mutations in the dopa decarboxylase gene leading to reduced AADC enzyme activity. Patients with AADC deficiency may experience delayed cognitive and speech development. Eladocagene exuparvovec is a recombinant adeno-associated viral vector carrying the human AADC gene coding sequence.
Methods: Eladocagene exuparvovec was administered bilaterally into the putamen of 28 children with AADC deficiency in 3 clinical trials (AADC-CU/1601 [8 patients, completed], AADC-010 [10 patients, completed], and AADC-011 [10 patients at 26 February 2020 cutoff date, ongoing]). Patients received 1.8 × 10^11 vg (n=21) or 2.4 × 10^11 vg (n=7; AADC-011)]. Cognition and language changes were assessed using Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT; N=8) and Bayley Scales of Infant Development, 3rd edition (Bayley-III; N=20). Both tools measure pediatric development and include cognitive and language subscales.
Results: CDIIT showed improvements in cognitive and language skills as early as 6 months, which were maintained up to 60 months. Bayley-III showed gradual, sustained improvement up to 60 months (Figure 1). Mean change from baseline, total language score was 46.5% after 12 months (n=17), 62.7% after 24 months (n=15), 80.5% after 36 months (n=10), 108.3% after 48 months (n=8), and 110.7% after 60 months (n=4). Significant improvements in subscale scores were observed 24 months post-treatment.
Conclusions: Results demonstrate the efficacy of eladocagene exuparvovec in improving cognition and communication in patients with AADC deficiency, indicating that gene therapy may successfully target neurotransmitters affected by AADC deficiency and may improve quality of life.
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
Antonia Wang
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 caused by mutations in the dopa decarboxylase gene leading to reduced AADC enzyme activity. Patients with AADC deficiency may experience delayed cognitive and speech development. Eladocagene exuparvovec is a recombinant adeno-associated viral vector carrying the human AADC gene coding sequence.
Methods: Eladocagene exuparvovec was administered bilaterally into the putamen of 28 children with AADC deficiency in 3 clinical trials (AADC-CU/1601 [8 patients, completed], AADC-010 [10 patients, completed], and AADC-011 [10 patients at 26 February 2020 cutoff date, ongoing]). Patients received 1.8 × 10^11 vg (n=21) or 2.4 × 10^11 vg (n=7; AADC-011)]. Cognition and language changes were assessed using Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT; N=8) and Bayley Scales of Infant Development, 3rd edition (Bayley-III; N=20). Both tools measure pediatric development and include cognitive and language subscales.
Results: CDIIT showed improvements in cognitive and language skills as early as 6 months, which were maintained up to 60 months. Bayley-III showed gradual, sustained improvement up to 60 months (Figure 1). Mean change from baseline, total language score was 46.5% after 12 months (n=17), 62.7% after 24 months (n=15), 80.5% after 36 months (n=10), 108.3% after 48 months (n=8), and 110.7% after 60 months (n=4). Significant improvements in subscale scores were observed 24 months post-treatment.
Conclusions: Results demonstrate the efficacy of eladocagene exuparvovec in improving cognition and communication in patients with AADC deficiency, indicating that gene therapy may successfully target neurotransmitters affected by AADC deficiency and may improve quality of life.
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
Antonia Wang
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