Hereditary Spastic Paraplegia (HSP)
Hereditary spastic paraplegia (HSP) is a type of upper motor neuron disease (UMND) and is considered to be complex and intractable. To help solve the therapeutic puzzles HSP poses, Protheragen has dedicated advanced technologies and specialists to build effective therapies. We offer complete assistance from design to deployment which will greatly accelerate your journey from drug candidate development to market.
Introduction to Hereditary Spastic Paraplegia (HSP)
Hereditary spastic paraplegia (HSP) comprises a genetically heterogeneous group of neurodegenerative disorders characterized by progressive lower-limb spasticity and weakness due to corticospinal tract degeneration. With over 80 identified genetic subtypes, HSP exhibits both autosomal dominant (e.g., SPAST/SPG4) and recessive (e.g., CYP7B1/SPG5) inheritance patterns. Epidemiologically, HSP prevalence ranges from 1-9/100,000 globally, with significant variability across subtypes.
Fig.1 Hereditary spastic paraplegia (HSP) patients have shown the clinical manifestations, and the treatment and management options available to date. (Meyyazhagan A, et al., 2022)
Pathogenesis of Hereditary Spastic Paraplegia (HSP)
The most common cause of hereditary spastic paraplegia (HSP) is mutation in SPAST (SPG4) which makes up 40 percent of dominantly inherited cases. SPAST causes microtubule dysfunction and problems with axonal transport. Defects in SPG 11 and SPG 15 cause autophagy-lysosomal dysfunction from protein aggregation. These mutations result in "dying-back" axonopathy affecting the longest neurons in the corticospinal tract leading to progressive spasticity and weakness.
Fig.2 Schematic representation of the cellular process involved in the pathology of hereditary spastic paraplegia (HSP). (Meyyazhagan A, et al., 2022)
Therapeutic Development for Hereditary Spastic Paraplegia (HSP)
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
| Dalfampridine | Potassium channel blocker, improves axonal conduction | Voltage-gated potassium channels | NCT05613114 | Phase II/III |
| Botulinum Toxin | Presynaptic neuromuscular blockade, reduces spasticity | SNARE proteins | NCT02604186 | Approved |
| Calcium Folinate | Folinic acid derivative, may enhance mitochondrial function | Dihydrofolate reductase, mitochondrial folate pathways | NCT06478238 | 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
Specializing in comprehensive solutions for hereditary spastic paraplegia (HSP), Protheragen integrates diagnostic development with cutting-edge in vitro diagnostic (IVD) kits for early disease identification. Our therapeutic development pipeline leverages exclusive disease models, such as physiologically representative blood-brain barrier (BBB) models, to expedite the exploration and authentication of central nervous system (CNS) targeted treatments.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
- SPAST Knockout Model
- Reep1 Knockout Model
- Ap4b1 Knockout Model
- SPG11 Knockout Model
- Zfyve26 Knockout Model
- Other Models
Protheragen is steadfastly dedicated to meticulously validating and optimizing therapies for hereditary spastic paraplegia (HSP) through a thorough series of pharmacodynamics (PD), pharmacokinetics (PK) and toxicology studies. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Meyyazhagan A, Kuchi Bhotla H, Pappuswamy M, et al. The puzzle of hereditary spastic paraplegia: from epidemiology to treatment[J]. International Journal of Molecular Sciences, 2022, 23(14): 7665.