Batten disease (BD), caused by mutations in the CLN3 gene, is a neurodegenerative disorder characterized by blindness, seizures and progressive motor, psychiatric and cognitive decline. Galactosyl-ceramide (GC) depletion is validated as a therapeutic target for Batten disease (BD) in preclinical studies in which galactosyl- ceramide replacement with a GC analog (SNB-4050) is dramatically neuroprotective. SNB-4050 is superior to natural GC due to its increased aqueous solubility and greatly improved brain penetration; however, preliminary animal data indicates that at the dose tested (20 mg/Kg; i.p.; QD) in BD animals there were variable levels of improvement on different measures of the neurophysiological effects (e.g. a reduction in lipofuscin (protein aggregate), astrocytosis/microglia activation and ceramide levels and improvement in one motor function test (pole climbing). Our goal is to determine the full extent of biological improvements that can be attained by administration of SNB-4050 in the Cln3?ex7/8 knock-in BD mouse (on the 129S6/SvEv genetic background), a mouse model more representative of human disease, by performing a dose ranging study of drug (i.p.) that includes higher doses to enhance brain delivery. GC replacement therapy with SNB-4050 offers a unique approach for slowing the progression of BD and could represent a major advance in BD therapy.

Public Health Relevance

Galactosyl-ceramide (GC) depletion is validated as a therapeutic target for Batten's disease (BD) in preclinical studies in which galactosyl-ceramide replacement with a GC analog (SNB-4050) is dramatically neuroprotective. SNB-4050 is superior to natural GC due to its increased aqueous solubility and greatly improved brain penetration; however, preliminary animal data indicates that at the dose tested (20 mg/Kg; i.p.; QD) in BD animals there were variable levels of improvement on different measures of the neurophysiological effects (e.g. a reduction in lipofuscin (protein aggregate), astrocytosis/microglia activation and ceramide levels and improvement in one motor function test (pole climbing). Our goal is to determine the full extent of biological improvements that can be attained by administration of SNB-4050 in the Cln3?ex7/8 knock-in BD mouse (on the 129S6/SvEv genetic background), a mouse model more representative of human disease, by performing a dose ranging study of drug (i.p.) that includes higher doses to enhance brain delivery. GC replacement therapy with SNB-4050 offers a unique approach for slowing the progression of BD and could represent a major advance in BD therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43NS095376-01A1
Application #
9199260
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Morris, Jill A
Project Start
2016-09-01
Project End
2017-08-31
Budget Start
2016-09-01
Budget End
2017-08-31
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Seneb Biosciences, Inc.
Department
Type
DUNS #
961713588
City
North Wales
State
PA
Country
United States
Zip Code
19454