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NRI to commence project focused on Atypical TPP1 Deficiency, a disorder closely related to Late Infantile Neuronal Ceroid Lipofuscinosis 2

HOUSTON -- May 2, 2016 --  The Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children's Hospital in Houston, Texas today announced the commencement of a new project to explore whether the pharmacological activation of transcription factor EB (TFEB) can be effective in promoting cellular clearance in Atypical TPP1 Deficiency (aka SCAR 7), a subset of Late Infantile Neuronal Ceroid Lipofuscinosis 2 (CLN2).  While TPP1 deficiencies are typically associated with CLN2, a subset of cases has been described as milder, which can be explained by the comparatively higher residual activity of TPP1 in Atypical TPP1 patients compared to CLN2 patients.  Atypical TPP1 Deficiency and CLN2 are caused by mutations in the TPP1/CLN2 gene resulting in deficient activity of the enzyme tripeptidyl peptidase 1 (TPP1). In the absence of TPP1, lysosomal storage materials, normally metabolized by this enzyme, accumulate in many organs, particularly in the brain. Buildup of these storage materials in the cells of the nervous system contribute to progressive and relentless neurodegeneration which manifests as loss of cognitive, motor, and other functions.  Patients typically present initially with language delay followed by movement disorders, motor deterioration, dementia, and early death. During the later stages of the diseases, feeding and tending to everyday needs become very difficult.  Currently, there is no cure for TPP1 Deficiency or CLN2.

The project will be led by Dr. Marco Sardiello, assistant professor at Baylor College of Medicine and investigator at the Jan and Dan Duncan Neurological Research at Texas Children's Hospital. This project is highly translational because it makes use of drugs and strategies that are readily available for clinical translation; is highly personalized because it focuses on Atypical TPP1 Deficiency, which is associated with partial TPP1 function and specific disease symptoms; and is of broad interest because it aims to make use of tools and concepts that can be extended to additional conditions of impaired metabolism and neurodegeneration.  Dr. Marco Sardiello is devoted to developing innovative therapies to treat lysosomal storage disorders, which are the most common neurodegenerative diseases of childhood. Dr. Sardiello found that the TFEB is a master gene for the lysosomal network, able to modulate the biogenesis and activity of lysosomes. TFEB could serve as a therapeutic target to enhance cellular clearance in lysosomal storage disorders and neurodegenerative diseases.

This project is funded by the friends and family of Fighting for Maya.


To learn more about the Jan and Duncan Neurological Institute at Texas Children's and their important work, Click Here.

To learn more about Dr. Marco Sardiello, Click Here.