Spark Therapeutics (ONCE) New target - Neurodegenerative Disease - Maintaining BUY

November 12, 2015 10:10am

Pre-clinical data demonstrated delay in onset and progression of a form of Batten Disease

ONCE unveiled today its first gene therapy program targeting a disease of the central nervous system (CNS).

 Findings published in the current issue of Science Translational Medicine (http://stm.sciencemag.org/content/7/313/313ra180 ) provide preclinical proof of concept for Spark’s SPK-TPP1 program. The study demonstrates the potential of a one-time administration of Spark’s gene therapy to delay onset and progression of a form of Batten disease, a fatal neurological disorder that begins in early childhood.

The Bottom Line: The study showed in a large preclinical model of TPP1 deficiency that one-time administration of recombinant adeno-associated viral (AAV) vector produced steady expression of the enzyme in the cerebrospinal fluid, and resulted in demonstrable clinical benefits across multiple endpoints.

• Administration <of Spark’s AAV serotype 2 vector delivering the TPP1 gene to the ependymal cells of the brain ventricular system > delayed onset of clinical symptoms and disease progression, protection from cognitive decline and extension of lifespan relative to untreated controls;

• Importantly, the novel delivery approach used in the study produced effective distribution of the enzyme throughout the central nervous system, as evidenced by immunohistochemistry and enzyme activity assay;

• Based on these results, Spark plans to initiate IND-enabling studies this year.

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A form of Batten disease, TPP1 deficiency causes severe early childhood neurodegenerative disease that results in motor and mental decline, seizures and visual deficits, and leads to death in a majority of cases during early childhood. The autosomal recessive disease is caused by mutations in the TPP1 gene, leading to a deficiency of the soluble lysosomal enzyme tripeptidyl peptidase 1, or TPP1. TPP1 deficiency, can also be known as CLN2 disease, is the first in a broad portfolio of CNS disease targets that Spark intends to pursue under rights it obtained from the University of Iowa.

• The preclinical model described in this study was also used in an enzyme replacement therapy program currently in development by another company for the same form of Batten disease. That program subsequently demonstrated initial clinical proof of concept in early stage human clinical trials.