Intranasally-Delivered Therapy for Treatment of Amyotrophic Lateral Sclerosis

Intranasal delivery of dantrolene nanoparticles can improve motor neuron function, muscle strength, and movement coordination and can offer therapeutic benefits for treatment of Amyotrophic Lateral Sclerosis (ASL).
Problem:
ALS a neurodegenerative disease with poor prognosis. ALS is categorized into the familial and sporadic types, with the former accounting for about 10% of cases and the latter the remaining 90% with unknown etiology. Existing therapeutic approaches for ALS involve management of the symptoms and improving quality and length of life. It is paramount to discover and translate treatments of greater efficacy to further extend the quality and length of life post diagnosis and, ultimately, provide a cure.
Technology:
Dr. Wei’s laboratory at the University of Pennsylvania Medical School has previously demonstrated that intranasal delivery of dantrolene in nanoparticle formulation led to a significant increase in dantrolene’s concentration and duration in the brain and an increase in the brain/blood concentration ratio, especially in the aged brain, compared to the oral or subcutaneous administration methods. In an ALS animal model itranasal dantrolene nanoparticles robustly inhibited motor neuron dysfunction and movement discoordination and muscle weakness, associated with robust inbhition of elevated blood biomarker of neurodegeneration, neurofilament light chain. This suggests that intranasal delivery of dantrolene nanoparticles can potentially be used for treatment of ASL.

In addition, Dr. Wei has shown that intranasal use of dantrolene can reduce inflammation-induced depression symptoms and reduce memory loss and AD pathologies in AD animal models.
Advantages:

Use of clinically available and well studied drugs
Increased therapeutic effect
Reduced systemic side effects
Potential dose reduction while maintaining therapeutic effectiveness

Stage of Development:

Preclinical Discovery

Intranasal dantrolene nanoparticles robustly and significantly inhibit impairments in motor coordination and movement balance Overall motor coordination and balance were evaluated at the end of a 30-day treatment period (No treatment (NO TX), intranasal vehicle (IN-VEH) or intranasal dantrolene nanoparticles (IN-DAN) at 120 days of age, using the beam balance test
Intellectual Property: