Propionic Acidemia (PA)
The primary therapeutic challenge in propionic acidemia (PA) lies in simultaneously correcting the underlying PCC enzyme deficiency while managing the downstream metabolic crises. Protheragen boasts a talented team of researchers and scientists with extensive expertise in PA. They are deeply committed to pioneering the development of cutting-edge therapies for PA, aiming to address unmet therapeutic needs and advance targeted therapeutics in the field.
Introduction to Propionic Acidemia (PA)
Propionic acidemia (PA) is a life-threatening autosomal recessive organic acid disorder caused by deficiency of propionyl-CoA carboxylase (PCC), a mitochondrial enzyme critical for the catabolism of branched-chain amino acids (isoleucine, valine, methionine, threonine) and odd-chain fatty acids. This metabolic block results in toxic accumulation of propionate, propionyl-CoA, and related metabolites, leading to multi-organ dysfunction.
Fig.1 Schematic description of pathophysiology of propionic acidemia (PA). (Zlamy M, et al., 2022)
Pathogenesis of Propionic Acidemia (PA)
Propionic acidemia (PA) results from PCCA/PCCB mutations causing propionyl-CoA carboxylase (PCC) deficiency, disrupting propionate metabolism. This leads to toxic accumulation of propionyl-CoA and derivatives, which inhibit the urea cycle (causing hyperammonemia) and TCA cycle (inducing lactic acidosis), while depleting carnitine stores. The resulting mitochondrial dysfunction drives multi-organ damage, particularly in the brain (neurotoxicity) and heart (cardiomyopathy).
Fig.2 Metabolic pathway of propionate. (Medina-Torres E A, et al., 2021)
Therapeutic Development for Propionic Acidemia (PA)
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
| Carglumic Acid | Synthetic analog of N-acetylglutamate that activates carbamoyl phosphate synthetase 1 (CPS1) | N-acetylglutamate synthase (NAGS) | NCT05040178 | Approved |
| N-carbamyl-L-glutamate | Activates CPS1 to enhance urea cycle function and reduce ammonia | CPS1 enzyme | NCT01599286 | Phase III |
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
Protheragen specializes in providing cutting-edge diagnostic and therapeutic development services for rare neurometabolic disease, including propionic acidemia (PA). We focus on creating advanced disease models to better understand PA pathogenesis, and we utilize innovative blood-brain barrier (BBB) models to enhance the delivery and efficacy of therapeutic compounds. Through our comprehensive approach, we aim to accelerate the development of accurate diagnostic kits and effective treatments tailored to PA.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
- PCCA Knockout Model: This complete PCCA knockout exhibits neonatal lethality with severe metabolic acidosis.
- Pcca−/− (A138T) Model: This hypomorphic knock-in replicates human PA pathology with residual PCC activity (~2%).
Focusing on preclinical research, Protheragen offers comprehensive pharmacodynamic (PD), pharmacokinetic (PK), and toxicology study services to support the development and regulatory approval of potential therapies. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Zlamy M, Zöggeler T, Bachmann M, et al. Immunological memory and affinity maturation after vaccination in patients with propionic acidemia[J]. Frontiers in Immunology, 2022, 13: 774503.
- Medina-Torres E A, Vela-Amieva M, Galindo-Campos L, et al. Abnormalities in subsets of B and T cells in Mexican patients with inborn errors of propionate metabolism: observations from a single-center case series[J]. Allergologia et Immunopathologia, 2021, 49(1): 101-106.