# Manufacture of an intracerebroventricular Enzyme Replacement Therapy for CLN1 Batten Disease

> **NIH NIH R44** · COLLABORATIONS PHARMACEUTICALS, INC. · 2022 · $1,499,923

## Abstract

Summary
The neuronal ceroid lipofuscinoses (NCLs) are a group of incurable neurodegenerative storage disorders
primarily affecting the brain and the retina of children and young adults, leading to dementia, blindness, epilepsy,
and early death, with a prevalence of approximately 1.5 to nine per million population (1.3 to 7 per 100,000 live
births). The infantile onset form CLN1 disease is caused by mutations in the CLN1/PPT1 gene, which codes for
the lysosomal enzyme palmitoyl-protein thioesterase-1 (PPT1) resulting in a reduction or absence of enzyme
activity. CLN1 disease usually presents between 6 and 24 months of age and there are 2-3 children with this
form identified each year and currently 24 known children with CLN1 in the US and 11 in Brazil (with likely many
more undiagnosed). There are currently no treatments available other than palliative therapies and the disease
is fatal. Human recombinant PPT1 (rhPPT1) expressed in CHO cells has been previously reported to modify
disease phenotypes following a single intrathecal (IT) and intravenous (IV) administration in PPT1 deficient mice
(Ppt1-/-). After successful completion of our Phase I SBIR in which we met or exceeded our milestones IT,
intracerebroventricular (ICV) as well as combined routes of delivery were compared. We demonstrated that
monthly administration of rhPPT1 via ICV produced statistically significant treatment effects in Ppt1-/- mice, such
as rescue of more than 60% PPT1 enzyme activity decreased secondary enzyme levels, decreased the loss of
neurons in all regions of brain and spinal cord and improved gait and rotarod results. This also illustrated that
delivery of enzyme via this route alone may be sufficient rather than using in combination with IT dosing. We
have now developed our own PPT1 cell line using CHO-DG44, that is scalable for GMP manufacture and
performed initial purification development strategies and we are developing a diagnostic tool for CLN1. The
CLN1 ERT data clearly points to ICV dosing as ideal for future studies, which is also a preferred route according
to physicians. Collaborations Pharmaceuticals, Inc (CPI) now proposes in this Phase II SBIR to file a preIND
(with the assistance of RTI International and Foresight Biosciences), perform manufacturing of PPT1 (with the
assistance of Goodwin Biotechnology, Inc. and CMC consultant Dr. Stefan Proniuk), conduct rat and dog IND
enabling toxicology studies (with the assistance of Charles River Laboratories) and ultimately filing an IND (with
the assistance of RTI International and Foresight Biosciences). We will hire these experienced consultants and
clinical research organizations to assist us throughout the process as they have years of experience. These
collaborations will enable us to cost effectively and more rapidly translate this potential treatment to the clinic
that can potentially save the lives of children living with this devastating disease. We have already obtained an
Orphan Drug Designation an...

## Key facts

- **NIH application ID:** 10483470
- **Project number:** 2R44NS107079-02A1
- **Recipient organization:** COLLABORATIONS PHARMACEUTICALS, INC.
- **Principal Investigator:** SEAN EKINS
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,499,923
- **Award type:** 2
- **Project period:** 2018-09-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10483470

## Citation

> US National Institutes of Health, RePORTER application 10483470, Manufacture of an intracerebroventricular Enzyme Replacement Therapy for CLN1 Batten Disease (2R44NS107079-02A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10483470. Licensed CC0.

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