X-linked Adrenoleukodystrophy (X-ALD)
X-linked adrenoleukodystrophy (X-ALD) causes progressive neurological damage, leading to inflammatory demyelination in the brain or degenerative axonal disease in the spinal cord. Protheragen leverages cutting-edge insights into the pathogenesis and genetic drivers of X-ALD to pioneer targeted therapies and precision animal models, accelerating preclinical drug development. Our goal is to offer reliable and end-to-end support to streamline your therapeutic development journey.
Overview of X-linked Adrenoleukodystrophy (X-ALD)
X-linked adrenoleukodystrophy (X-ALD) is a rare, X-linked recessive metabolic disorder with an estimated incidence of 1 in 17,000 to 1 in 21,000 male births, characterized by mutations in the ABCD1 gene that disrupt peroxisomal beta-oxidation, leading to toxic accumulation of very long-chain fatty acids (VLCFAs). The disease exhibits profound clinical heterogeneity, with core features including progressive neurodegenerative symptoms such as behavioral changes, vision loss, gait instability, and adrenal insufficiency (Addison's disease).
Fig.1 Molecular and biochemical features of X-linked adrenoleukodystrophy (X-ALD) phenotypes. (Parasar P, et al., 2024)
Pathogenesis of X-linked Adrenoleukodystrophy (X-ALD)
X-linked adrenoleukodystrophy (X-ALD) is fundamentally caused by mutations in the ABCD1 gene on the X chromosome, which encodes the adrenoleukodystrophy protein (ALDP), a peroxisomal transmembrane transporter. Loss of ALDP function impairs the ATP-dependent transport of very long-chain fatty acid (VLCFA)-CoA esters into peroxisomes, preventing their beta-oxidation and leading to systemic accumulation of toxic VLCFAs that subsequently drive neuroinflammatory demyelination, axonal degeneration, and adrenal insufficiency.
Fig.2 Simplified scheme of the main mechanisms that appear to contribute to X-linked adrenoleukodystrophy (X-ALD) phenotypes. (Bougnères P, Le Stunff C., 2025)
Therapeutic Development for X-linked Adrenoleukodystrophy (X-ALD)
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
| PXL065 | Selective PPAR-γ modulator that enhances lipid metabolism gene expression. | PPAR-γ | NCT05200104 | Phase IIa |
| Sobetirome | Thyroid hormone receptor beta agonist that induces fatty acid oxidation. | TRβ | NCT01787578 | Phase II |
| NV1205 | PPARδ agonist that stimulates fatty acid catabolism and reduces neuroinflammation. | PPARδ | NCT03196765 | Phase I/II |
| PXL770 | Direct AMPK activator that improves mitochondrial function and lipid oxidation. | AMPK | NCT05146284 | Phase IIa |
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
Recognizing the complexity of diagnosing and treating X-linked adrenoleukodystrophy (X-ALD), Protheragen is committed to building a team of experts to provide cutting-edge diagnostic and therapeutic development solutions. Our commitment lies in providing a variety of customized therapy development services to meet the diverse research needs of our customers. We also excel in generating precise disease models that are carefully engineered to replicate the unique features of X-ALD.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model Development
- Abcd1 Knockout Models: These models exhibit systemic VLCFA accumulation and adrenomedullary neuropathy (AMN)-like axonal degeneration, recapitulating the pathological features of adult-onset X-ALD.
- Other Models
At Protheragen, we are committed to supporting the development of innovative therapeutics through comprehensive preclinical research services, including pharmacodynamics (PD), pharmacokinetic (PK) and toxicology studies. Our customized approach addresses the unique challenges of your studies and helps you optimize your drug candidates for commercial success. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Parasar P, Kaur N, Singh J. Pathophysiology of X-linked adrenoleukodystrophy: updates on molecular mechanisms[J]. Journal of biotechnology and biomedicine, 2024, 7(2): 277.
- Bougnères P, Le Stunff C. Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy[J]. Genes, 2025, 16(5): 590.