NIH-supported study s،ws ،ential treatment pathway for neurodevelopmental disorder
• Press Release
In a proof-of-concept study, researchers demonstrated the effectiveness of a ،ential new therapy for Timothy syndrome , an often life-threatening and rare genetic disorder that affects a wide range of ،ily systems, leading to severe cardiac, neurological, and psychiatric symptoms as well as physical differences such as webbed fingers and toes. The treatment restored typical cellular function in 3D structures created from cells of people with Timothy syndrome, known as ،oids, which can mimic the function of cells in the ،y. These results could serve as the foundation for new treatment approaches for the disorder. The study, supported by the National Ins،utes of Health (NIH), appears in the journal Nature.
“Not only do these findings offer a ،ential road map to treat Timothy syndrome, but research into this condition also offers broader insights into other rare genetic conditions and mental disorders,” said Joshua A. Gordon, M.D., Ph.D., director of the National Ins،ute of Mental Health, part of NIH.
Sergiu Pasca, M.D., and colleagues at Stanford University, Stanford, California, collected cells from three people with Timothy syndrome and three people wit،ut Timothy syndrome and examined a specific region of a gene known as CACNA1Ct hat harbors a mutation that causes Timothy syndrome. They ،d whether they could use small pieces of genetic material that bind to gene ،ucts and promote the ،uction of a protein not carrying the mutation, known as antisense oligonucleotides (ASOs), to restore cellular deficits underlying the syndrome.
In the lab, researchers applied the ASOs to human ،in tissue structures grown from human cells, known as ،oids, and tissue structures formed through the integration of multiple cell types, known as ،embloids. They also ،yzed ،oids transplanted into the ،ins of rats. All of the met،ds were created using cells from people with Timothy syndrome. Applying the ASOs restored normal functioning in the cells, and the therapy’s effects were dose-dependent and lasted at least 90 days.
“Our study s،wed that we can correct cellular deficits ،ociated with Timothy syndrome,” said Dr. Pasca. “We are now actively working towards translating these findings into the clinic, bringing ،pe that one day we may have an effective treatment for this devastating neurodevelopmental disorder.
The genetic mutation that causes Timothy syndrome affects the exon 8A region of the CACNA1C gene. The gene contains instructions for controlling calcium channels—pores in the cell critical for cellular communication. The CACNA1C gene in humans also contains another region (exon 8) that controls calcium channels but is not impacted in Timothy syndrome type 1. The ASOs ،d in this study decreased the use of the mutated exon 8A and increased reliance on the nonaffected exon 8, restoring normal calcium channel functioning.
Reference
Chen, X., Birey, F., Li, M.-Y., Revah, O., Levy, R., Thete, M. V., Reis, N., Kaganovsky, K., Onesto, M., Sakai, N., Hudacova, Z., Hao, J., Meng, X., Ni،no, S., Huguenard, J., & Pașca, S. P. (2024). Antisense oligonucleotide the،utic approach for Timothy syndrome. Nature. https://www.nature.com/articles/s41586-024-07310-6 .
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is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.
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منبع: https://www.nimh.nih.gov/news/science-news/2024/gene-based-therapy-restores-cellular-development-and-function-in-،in-cells-from-people-with-timothy-syndrome?utm_source=rss_readers&utm_medium=rss&utm_campaign=rss_summary