THERAPEUTIC PIPELINE
The TTX-381 clinical trial for the treatment of ocular manifestations of CLN2 disease is currently underway at Great Ormond Street Hospital in London.
What is CLN2 Disease?
CLN2 disease (neuronal ceroid lipofuscinosis type 2), a form of Batten disease, is a rare, pediatric-onset, genetic disorder caused by an inherited mutation, or error, in the CLN2 gene. The CLN2 gene contains instructions to make an enzyme called tripeptidyl peptidase 1, or TPP1. TPP1 helps to break down and remove waste material from cells in the body. Deficiency in TPP1 enzyme activity causes waste materials to build up in the body’s cells, particularly in the brain and the eye, where they cause progressive damage and can lead to seizures, rapid loss of language and motor function, cognitive decline, vision loss/blindness, and premature death.
Vision Loss in CLN2 Disease
Visual impairment in CLN2 disease develops after cognitive, motor, and language impairments are already present. Changes in the retina, the layer of the eye affected by CLN2 disease, are associated with vision loss that progresses rapidly, leading to blindness. The onset and progression of these changes in the retina occur in both eyes at the same time. CLN2 disease typically causes vision loss, including in those diagnosed and treated early with enzyme replacement therapy in the brain. The CLN2 community has identified vision loss as a critically important need, since currently available treatments do not address or affect the eye.
How is TTX-381 Designed to Work?
Tern Therapeutics is developing an investigational gene therapy, TTX-381, designed to deliver a working copy of the TPP1 gene to the retina so that it can potentially make an ongoing supply of TPP1 enzyme to maintain the health of the retina and address vision loss in people with CLN2 disease.
How is TTX-181 Designed to Work?
Current treatment for the neurological effects of CLN2 disease involves biweekly intracerebroventricular (ICV) enzyme replacement therapy (ERT) with a human recombinant form of TPP1, cerliponase alfa, via an indwelling port.(1) While ERT slows progression of motor loss, it does not stop or reverse most manifestations of the disease.(2) Tern Therapeutics is developing an investigational gene therapy, TTX-181, designed to deliver a working copy of the TPP1 gene to the brain via the cerebrospinal fluid (CSF), so that it can potentially make an ongoing supply of TPP1 enzyme to prevent worsening of neurological degeneration in people with CLN2 disease.
(1) Schulz A, et al. N Engl J Med. 2018;378(20):1898-1907.
(2) Takahashi K, et al. J Clin Invest. 2023;133(12):e165908.