Glutaric Acidemia Type 1 (GA1)
Glutaric acidemia type 1 (GA1) is a genetic condition that affects metabolism and the nervous system, and is characterized by damage to the basal ganglia. Without treatment, it can lead to an acute encephalopathy crisis or progressive dystonia. Protheragen is focused on diagnostic and therapeutic gaps to advance GA1 management. As a dependable partner for GA1 therapeutic research, we offer extensive scientific services with an unwavering commitment to quality.
Introduction to Glutaric Acidemia Type 1 (GA1)
Glutaric acidemia type 1 (GA1) is an inherited neurometabolic disorder associated with an enzyme deficiency due to GCDH gene mutations located on 19p. It is characterized by the deficient activity of glutaryl-CoA dehydrogenase (GCDH), an enzyme responsible for the breakdown of lysine, hydroxylysine, and tryptophan. If untreated, the disorder causes irreversible damage to the striatum and the basal ganglia due to neurotoxic metabolites, like glutaric acid (GA), 3-hydroxyglutaric acid (3-OH-GA), and glutarylcarnitine (C5DC), which are produced in excess.
Fig.1 Disorders of lysine and tryptophan metabolism in glutaric acidemia type 1 (GA1). (Li Q, et al., 2021)
Pathogenesis of Glutaric Acidemia Type 1 (GA1)
Glutaric acidemia type 1 (GA1) is associated with a particular variant of a metabolic disorder characterized by a GCDH mutation, which leads to a deficiency in glutaryl-CoA dehydrogenase. This, in turn, results in the toxic build-up of glutaric acid and 3-hydroxyglutarate, which damages the striatal neurons by means of NMDA receptor-mediated excitotoxicity as well as mitochondrial and oxidative stress. Along with the aforementioned, the disorder also leads to the catabolic stress which causes an acute encephalopathy crisis.
Fig.2 Pathophysiology of glutaric acidemia type 1 (GA1). (Strauss K A, et al., 2020)
Therapeutic Development for Glutaric Acidemia Type 1 (GA1)
| Drug Names | Mechanism of Action | Targets | Research Phase |
| Levocarnitine | Replenishes free carnitine to conjugate with glutaryl-CoA, forming excretable glutarylcarnitine | Glutaryl-CoA metabolism (mitochondrial) | Approved |
| Riboflavin (B2) | Stabilizes mutant GCDH enzyme as FAD cofactor, enhancing residual activity | Flavin-binding domain of GCDH enzyme | Approved |
| VGM-R02b | AAV-mediated liver-directed gene therapy delivering functional GCDH gene | Hepatic GCDH enzyme restoration | Phase I |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
As a preclinical research service provider for glutaric acidemia type 1 (GA1), Protheragen provides end-to-end diagnostic and therapeutic development solutions. We excel in building physiologically relevant models, including in vitro models, animal models, and specialized blood-brain barrier (BBB) models, to enable comprehensive biomarker discovery, target validation, and CNS drug efficacy optimization.
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Disease Model Development Services
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Specializing in comprehensive preclinical assessment, Protheragen offers professional pharmacodynamic (PD), pharmacokinetic (PK) and toxicology research services to accelerate the therapeutic development of glutaric acidemia type 1 (GA1). If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Li Q, Yang C, Feng L, et al. Glutaric acidemia, pathogenesis and nutritional therapy[J]. Frontiers in Nutrition, 2021, 8: 704984.
- Strauss K A, Williams K B, Carson V J, et al. Glutaric acidemia type 1: treatment and outcome of 168 patients over three decades[J]. Molecular genetics and metabolism, 2020, 131(3): 325-340.