In rodent models, introduction of neuroprotective protein slowed disease progression and increased lifespan

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord responsible for voluntary movement and muscle control.

In a new study, published on 11 July 2022 in the journal Theranostics, researchers at the University of California San Diego School of Medicine report that a gene therapy approach, developed at UC San Diego, measurably delayed the disease onset in humanized mouse and rat models of familial disease. ALS, an inherited form of the disease that runs in families. (Most cases of ALS are sporadic, of cause unknown, although environmental and genetic factors may play a role.)

In previous research, lead author Brian P. Head, PhD, assistant professor in the Department of Anesthesiology at UC San Diego University of Medicine and health researcher at VA San Diego Healthcare Procedure and his colleagues had crossed a mouse model genetically modified to express a neuroprotective protein called caveolin-1 with a transgenic mouse model of ALS. The double-transgenic model showed better motor function and longer survival. synapsin-caveolin-1 (AAV9-SynCav1) in the spinal cord of familial ALS mice to see if it would delay disease development and preserve physical drive and mobility.

Researchers found that SynCav1 protected and preserved motor neurons in the spinal cord and extended longevity in mice. Subsequent experiments with a rat model of ALS produced similar results.

“These data suggest that SynCav1 could serve as a novel gene therapy for the neurodegenerative conditions of ALS and other forms of central nervous system disease of unknown etiology,” the authors wrote, calling for further studies.

The Theranostics article follows a study published in 2021 in which Head and colleagues used a SynCav1 gene therapy approach to prevent learning and memory loss in a mouse model of Alzheimer’s disease (AD) , a key step to eventually test the approach in humans with the neurodegenerative disease.

“Since the neuroprotective efficacy afforded by SynCav1 occurred independent of targeting of the known toxic monogenic protein (i.e. mutant hSOD1), these results suggest that SynC av1 could serve as a novel gene therapy for other neurodegenerative conditions besides ALS and AD,” the leader said. “However, it is essential that further studies determine the effect of SynCav1 on disease progression at later stages of the disease.”

The incidence of SLA is around 3 to 5 per 100 000 people worldwide. The disease affects approximately 000 000 people in the United States. Currently approved pharmaceutical treatments, such as Rilutek and Radicava, can slow disease progression and improve quality of life, but there is no cure. The average survival time after diagnosis is two to five years.

SynCav1 gene therapy is patented by UC San Diego and the Department of Veterans Affairs, and licensed to Eikonoklastes Therapeutics, based in Cincinnati, Ohio.

Co-authors: Shanshan Wang, Taiga Ichinomaya, Paul Savchenko, Donsheng Wang, Xiaojing Li, Tiffany Duong, Wenxi Li, Jacqueline A. Bonds, Atushi Miyanohara, David M. Roth, Hemal H. Patel, Piyush M. Patel, and Martin Marsala, all at UC San Diego Atsushi Sawada, Ryukyus University, Japan Eun Jung Kim, UC San Diego, and Yonsei University Higher education of Drugs, South Korea.

2022 2022

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