Spinal Bulbar Muscular Atrophy (SBMA)
Spinal and bulbar muscular atrophy (SBMA) is classified as a rare inherited neuromuscular condition. Protheragen has actively focused on SBMA research, which now places the company in a leading position for developing advanced treatment approaches aimed at improving the disease management paradigm of SBMA. Our company regards you as the most trusted partner in the drug development research and offers unmatched support to address all your research preferences
Introduction to Spinal Bulbar Muscular Atrophy (SBMA)
Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is due to the mutation of CAG trinucleotide repeats (over 38) in the androgen receptor gene causing an X-linked recessive disorder. This genetic condition results in the progressive degeneration of lower motor neurons located in the spinal cord and brainstem regions. Patients with SBMA usually present in adulthood with symptoms such as weakness of proximal muscles, muscle cramps, dysarthria as well as dysphagia.
Fig.1 Peripheral androgen receptor genetic inhibition resolves disease in mouse models of spinal and bulbar muscular atrophy. (Lieberman A P, et al., 2014)Pathogenesis of Spinal Bulbar Muscular Atrophy (SBMA)
Spinal and bulbar muscular atrophy (SBMA) is caused by a toxic gain-of-function mechanism due to CAG repeat expansions in the androgen receptor (AR) gene, resulting in mutant AR proteins containing polyglutamine (polyQ) tracts. These proteins misfold and form intranuclear aggregates within motor neurons, disrupting proteostasis, impairing transcriptional processes, damaging mitochondria, and initiating cell-autonomous apoptosis. The pathology is dependent on androgens because bound ligands evoke nuclear translocation and accumulation of toxic AR, resulting in selective degeneration of lower motor neurons in the spinal cord and brainstem.
Therapeutic Development for Spinal Bulbar Muscular Atrophy (SBMA)
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
| Mexiletine Hydrochloride | Sodium channel blocker; reduces muscle hyperexcitability and may lower toxic androgen effects | Voltage-gated sodium channels | NCT06862596 | Phase II |
| Clenbuterol | β-2 adrenergic agonist; promotes muscle hypertrophy and slows muscle atrophy | β-2 adrenergic receptor | NCT06169046 | Phase II |
| BVS857 | Recombinant IGF-1 mimetic; aims to promote muscle growth and survival | IGF-1 receptor | NCT02024932 | Phase II |
| Dutasteride | 5α-reductase inhibitor; reduces conversion of testosterone to dihydrotestosterone (DHT), lowering toxic androgen effects in SBMA | 5α-reductase | NCT00303446 | Phase II |
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
To advance the effective management of spinal and bulbar muscular atrophy (SBMA), Protheragen offers comprehensive diagnostic and therapeutic development services. With a focus on the diverse molecular mechanisms driving SBMA, we are dedicated to developing innovative and targeted therapies that address the significant unmet medical needs. Our team excels in creating highly accurate disease models, enabling rigorous evaluation of the safety, efficacy, and mechanism of action of potential therapeutics.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
- AR(65) Transgenic Models: Expresses full-length AR cDNA containing 65 CAG repeats and exhibits a mild phenotype.
- AR(120) Transgenic Models: Expresses the full-length AR cDNA containing 120 CAG repeats and exhibits progressive muscle weakness and atrophy.
At Protheragen, we are committed to validating and optimizing therapies for spinal and bulbar muscular atrophy (SBMA) 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.
Reference
- Lieberman A P, Yu Z, Murray S, et al. Peripheral androgen receptor gene suppression rescues disease in mouse models of spinal and bulbar muscular atrophy[J]. Cell reports, 2014, 7(3): 774-784.