Primary Progressive Aphasia (PPA)
Developing treatments for primary progressive aphasia (PPA) is challenged by the condition's diverse presentation and the absence of established biomarkers. To tackle the intricacies of PPA management, Protheragen has directed substantial investment into advanced technology platforms and expert professionals dedicated to novel therapeutic innovation. Our services is designed to accelerate every stage of your program, guiding promising drug candidates efficiently to market entry.
Introduction to Primary Progressive Aphasia (PPA)
Primary progressive aphasia (PPA) is a focal neurodegenerative disorder marked by a gradual decline in language capabilities while memory and behavioral functions remain relatively intact in early stages. This clinical presentation highlights the preferential degeneration of the language-dominant left-hemisphere networks. PPA is presently categorized into three recognized variants: nonfluent/agrammatic (nfvPPA), semantic (svPPA), and logopenic (lvPPA). Each variant is associated with a specific pattern of linguistic deficits and characteristic neuroanatomical involvement.
Fig.1 Proposed pathophysiology of primary progressive aphasia (PPA). (Belder C R S, et al., 2024)
Pathogenesis of Primary Progressive Aphasia (PPA)
The pathogenesis of primary progressive aphasia (PPA) primarily involves selective vulnerability of language networks to distinct proteinopathies: nonfluent PPA (nfvPPA) is driven by tau aggregation in frontal speech areas, semantic PPA (svPPA) by TDP-43 pathology in anterior temporal lobes, and logopenic PPA (lvPPA) by Alzheimer's-type amyloid/tau pathology in temporoparietal regions, with genetic factors (e.g., GRN, C9orf72) and network-specific neurodegeneration collectively disrupting language circuitry.
Fig.2 Neuroanatomical and cognitive profiles of the canonical syndromes of primary progressive aphasia (PPA). (Marshall C R, et al., 2018)
Therapeutic Development for Primary Progressive Aphasia (PPA)
| Drug Names | Mechanism of Action | Targets | Research Phase |
| Memantine | NMDA receptor antagonist; reduces glutamate-mediated excitotoxicity | NMDA receptors | Phase II |
| Etanercept | TNF-α inhibitor; reduces neuroinflammation potentially contributing to neurodegeneration | TNF-α | Early research |
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 serves as a preclinical research partner dedicated to primary progressive aphasia (PPA), delivering integrated diagnostic and therapeutic development solutions. Our strength lies in the creation of physiologically relevant models, ranging from in vitro systems and animal models to bespoke blood-brain barrier (BBB) models, thereby facilitating thorough biomarker discovery, rigorous target validation, and refinement of CNS drug efficacy.
Therapeutic Development Services
By Molecule Types
Protheragen is dedicated to offering a comprehensive spectrum of molecular drug development services aimed at meeting the therapeutic demands associated with primary progressive aphasia (PPA), ensuring tailored solutions for effective treatment interventions.
By Mechanism of Action
Our expertise lies in the development of multiple specialized neurotherapeutic drugs carefully designed to address the underlying mechanisms of primary progressive aphasia (PPA).
Disease Model Development Services
In Vitro Model Development
- Tau/TDP-43 Transgenic Models: Overexpression of mutant forms of tau or TDP-43 proteins, mimics the neurodegenerative pathology.
- PPA1-Knockout Models: Targeted deletion of the PPA1 gene to study its role in neuronal function and language networks.
Protheragen takes pride in offering comprehensive preclinical research services for primary progressive aphasia (PPA) using advanced disease models. These services encompass various aspects of drug research, including pharmacodynamics (PD), pharmacokinetics (PK), and safety evaluations, ensuring a holistic approach towards drug development in this challenging medical area. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Belder C R S, Marshall C R, Jiang J, et al. Primary progressive aphasia: six questions in search of an answer[J]. Journal of Neurology, 2024, 271(2): 1028-1046.
- Marshall C R, Hardy C J D, Volkmer A, et al. Primary progressive aphasia: a clinical approach[J]. Journal of neurology, 2018, 265: 1474-1490.