Flail Leg Syndrome (FLS)
Through progressive disability, loss of mobility, and increased demand for caregiving assistance, flail leg syndrome (FLS) causes notable socioeconomic strain. Using our pioneering work in FLS research as a springboard, Protheragen is now focused on developing new therapies that improve the management of FLS. We are your devoted allies in FLS drug development research, and we stand ready to provide fully tailored solutions to your research requirements.
Introduction to Flail Leg Syndrome (FLS)
Flail leg syndrome (FLS) or pseudopolyneuritic ALS is an uncommon variant of amyotrophic lateral sclerosis (ALS) marked by the predominance of lower motor neuron (LMN) features. It presents with progressive weakness distal to the lower limb, atrophy, and minimal upper motor neuron involvement. In contrast to classical forms of ALS, FLS is observed to progress much more slowly. It has a median survival of 8-10 years and occurs more frequently in men.
Fig.1 Representation of clinical compromise and progression in classical and atypical variants of amyotrophic lateral sclerosis (ALS). (Pinto W, et al., 2019)
Pathogenesis of Flail Leg Syndrome (FLS)
The pathogenesis of flail leg syndrome (FLS) includes the selective degeneration of lower motor neurons in the lumbosacral region due to genetic changes like C9ORF72 hexanucleotide expansions and SOD1 variants, along with mitochondrial dysfunction and TDP-43 proteinopathy. These factors combined cause disruptions in the RNA processing, axonal transport, and energetic homeostasis of distal motor neurons.
Fig.1 The Kaplan–Meier survival curves of different phenotypes in 186 patients with lower limb onset ALS. (Zhang H, et al., 2022)Therapeutic Development for Flail Leg Syndrome (FLS)
| Drug Names | Mechanism of Action | Targets | Research Phase |
| Tofersen | Antisense oligonucleotide that aims to reduce the synthesis of mutant superoxide dismutase 1 (SOD1) protein, potentially diminishing its toxic effects. | Mutant SOD1 mRNA | Approved |
| Riluzole | Inhibits glutamate release and blocks voltage-dependent sodium channels, reducing excitotoxicity in neurons. | Glutamate receptors, sodium channels | Approved |
| Masitinib | A selective tyrosine kinase inhibitor that targets inflammatory cells and may reduce neuroinflammation and neuronal damage. | Tyrosine kinases | 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
As a provider of preclinical research services, Protheragen strives to advance innovations in flail leg syndrome (FLS) by offering full range solutions from devising diagnostics and developing therapeutics to constructing accurate disease models and performing thorough preclinical validation. With our blood-brain barrier model, we can utalize drug concentration evaluations within the central nervous system (CNS) to determine its permeability as well as measure the exposure in relation to systemic toxicity. This ensures a more streamlined process for developing effective therapies.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
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- Patient-Derived Cell Model
- Neuronal Cell Model
- Glial Cell Model
- Co-Culture Model
- Brain Organoid
- Spinal Cord Organoid
In Vitro Model Development
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- BMAA Induced Model: Toxins like β-N-methylamino-L-alanine (BMAA) that may preferentially affect lower motor neurons.
- TARDBP Transgenic Model: Transgenic mice expressing TAR DNA-binding protein 43 (TARDBP) reflect the pathology observed in some cases of ALS.
At Protheragen, we are committed to validating and optimizing therapies for flail leg syndrome (FLS) through preclinical studies including pharmacodynamics (PD), pharmacokinetics (PK) and toxicology to ensure their successful regulatory approval. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Pinto W, Debona R, Nunes P P, et al. Atypical motor neuron disease variants: still a diagnostic challenge in neurology[J]. Revue Neurologique, 2019, 175(4): 221-232.
- Zhang H, Chen L, Tian J, et al. Differentiating slowly progressive subtype of lower limb onset ALS from typical ALS depends on the time of disease progression and phenotype[J]. Frontiers in Neurology, 2022, 13: 872500.