In a preliminary study, scientists showed how a possible new treatment for Timothy syndrome could be effective. Timothy syndrome is a rare and often life-threatening genetic disorder that impacts various bodily functions, causing serious heart, brain, and mental health symptoms, as well as physical abnormalities like joined fingers and toes.Psychiatric symptoms as well as physical differences like webbed fingers and toes can be treated to restore typical cellular function. 3D structures created from cells of people with Timothy syndrome, called organoids, can mimic the function of cells in the body. This could be the basis for new treatment approaches for the disorder. The study, supported by the National Institutes of Health (NIH), appears in the journal Nature. “Not only do these findings offer a potential road map to treat Timothy syndrome, but research into this condition also offers broader insights into other disorders with similar symptoms,”Joshua A. Gordon, M.D., Ph.D., who is the director of the National Institute of Mental Health, part of NIH, mentioned the challenges posed by rare genetic conditions and mental disorders. Sergiu Pasca, M.D., and his team at Stanford University, Stanford, California, conducted a study involving cells from individuals with and without Timothy syndrome. They focused on a specific region of a gene called CACNA1C, which contains a mutation responsible for Timothy syndrome. The researchers tested the use of small pieces of genetic material that can bind to gene products and promote the production of a protein without the mutation, referred to as antisense oligonucleotides.with Timothy syndrome using ASOs in both cell culture and in animal models,” said the senior author. “This is a promising step toward developing a potential therapy for this rare and currently untreatable disorder.”
The researchers believe that this study could pave the way for new treatment options for Timothy syndrome and potentially other genetic disorders. The next steps involve further testing the ASOs in animal models and refining the therapy for future clinical trials. The researchers hope that their work will lead to a better understanding of the disease and ultimately improve the lives of those affected by it.We are making progress in understanding the genetic mutation that causes Timothy syndrome,” stated Dr. Pasca. “Our goal is to use this knowledge to develop a treatment for this severe neurodevelopmental disorder.”
The mutation associated with Timothy syndrome affects the exon 8A region of the CACNA1C gene, which provides instructions for regulating calcium channels. These channels are crucial for cell-to-cell communication. Although the gene also contains another region (exon 8) that controls calcium channels, this region is not affected in Timothy syndrome type 1. The ASOs tested in this study are aimed at targeting the mutation in exon 8A.The use of the mutated exon 8A has been reduced and there is now greater reliance on the unaffected exon 8, which has helped to restore normal calcium channel functioning.
Â
