Developing precision medicines for neurodegenerative disease
In the next 20 years, neurodegenerative disease is expected to overtake cancer as the second leading cause of death worldwide. At the same time, progress in developing disease-modifying treatments has been slowed by the lack of novel insights into driver mechanisms of disease. Circumvent was formed with the mission of developing precision medicines for neurodegenerative disease, starting with Batten Disease.
We built an experienced team of scientists and clinicians to focus on diseases with high-fidelity, predictive animal models, a clear clinical development path, and the potential to reach the market quickly. Through our research and development of treatments for Batten Disease, we’ve uncovered new insights into brain-cell dysfunction that are common to numerous forms of neurological disease. We are now applying these insights across a variety of related diseases with diligence and precision.
We've developed novel insights into:
Synaptic function Protein localization Lysosomal function Autophagy
Our search for underlying biology has allowed us to characterize the palmitoylome with precision
We are investigating several therapeutic strategies for modulating the palmitoylome
This effort has broad potential to yield medicines for both rare and common forms of neurodegenerative disease
Our investigation into the palmitoylome has given us unique insights into the architecture of the synaptome and its effect on synaptic function
>50% of palmitoylated proteins are synaptic proteins, and conversely, >40% of synaptic proteins are palmitoylated
Modulating palmitoylation has effects on synaptic plasticity and neuronal differentiation, with broad therapeutics potential
Our priority is to meet the needs of patients through the development of precision medicines for rare neurological diseases. We listen to patients and caregivers and solicit advice to better understand expectations for therapies and guide our research and development efforts. Circumvent’s current drug programs are being developed for Batten Disease and other rare neurological disorders.
What is Batten Disease?
Batten disease is a group of rare neurodegenerative diseases that typically present during childhood and progress rapidly. Each subtype of Batten Disease is caused by a mutation in one of several genes that are important for normal brain function. Common symptoms include vision loss, seizures, delay and eventual loss of skills previously acquired, dementia, and abnormal movements. Although the different forms of the disease may present at different ages, they are all fatal, usually by the teens or early twenties.
At Circumvent, we are focused initially on CLN1 Batten Disease, which is one of the most common and most severe forms of Batten Disease. CLN1 Batten Disease is caused by a mutation in the CLN1 gene, which is responsible for removing a type of fatty acid called palmitate from proteins in the cell. When this gene is mutated, brain cells are unable to remove palmitate from proteins, which leads to rapid neurodegeneration early in childhood. Currently, there are no approved treatments for CLN1 Batten Disease.
Circumvent partners with Batten Disease patient organizations. These advocacy organizations support patients, families, and caregivers for these specific diseases and participate in research, advocacy, education and fundraising efforts.
Nader Al Nakouzi
Rachel M Johansson