The treatment restored typical cellular function in 3D structures created from cells of people with Timothy syndrome, known as organoids, which can mimic the function of cells in the body.
The study, supported by the National Institutes of Health (NIH), appears in the journal Nature.
Sergiu Pasca, M.D., and colleagues at Stanford University, Stanford, California, collected cells from three people with Timothy syndrome and three people without Timothy syndrome and examined a specific region of a gene known as CACNA1C that harbors a mutation that causes Timothy syndrome.
All of the methods were created using cells from people with Timothy syndrome.
“Our study showed that we can correct cellular deficits associated with Timothy syndrome,” said Dr. Pasca.
The genetic mutation that causes Timothy syndrome affects the exon 8A region of the CACNA1C gene.
The CACNA1C gene in humans also contains another region (exon 8) that controls calcium channels but is not impacted in Timothy syndrome type 1.
About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services.
An investigation funded by the NIH reveals a possible course of treatment for neurodevelopmental disorders.
A potential new therapy for Timothy syndrome, a rare and often life-threatening genetic disorder affecting many body systems and causing severe cardiac, neurological, and psychiatric symptoms in addition to physical abnormalities like webbed fingers and toes, was shown to be effective in a proof-of-concept study done by researchers. In organoids, three-dimensional structures made from the cells of individuals with Timothy syndrome that can mimic the function of human cells, the therapy restored normal cellular function. New approaches to treating the disorder may be based on these findings. The National Institutes of Health (NIH) funded the study, which was published in the journal Nature.
Joshua A. stated, “Research into Timothy syndrome offers broader insights into other rare genetic conditions and mental disorders, in addition to providing a potential road map to treat the condition.”. Gordon, Master of Design. Ph. C. , the head of the NIH’s National Institute of Mental Health.
Sergiu Pasca, Doctor of Design. , along with associates at Stanford University, Stanford, California, gathered cells from three individuals who had Timothy syndrome and three individuals who did not, and then looked at a particular area of a gene called CACNA1C that contains a mutation that causes Timothy syndrome. Antisense oligonucleotides (ASOs), which are short segments of genetic material that bind to gene products and stimulate the synthesis of a protein lacking the mutation, were tested for their potential to repair cellular deficiencies underlying the syndrome.
The human brain tissue structures grown from human cells, or organoids, and the tissue structures created by integrating different cell types, or assembloids, were subjected to the ASOs in the laboratory. Organoids that had been inserted into rats’ brains were also examined. Cells from individuals with Timothy syndrome were used to create each of the techniques. The treatment’s effects were dose-dependent and persisted for at least ninety days after the ASOs were applied, returning the cells to normal functioning.
“Our research demonstrated that cellular deficiencies linked to Timothy syndrome can be addressed,” Dr. Pasca stated. “We are now making a concerted effort to bring these discoveries into the clinic, raising the prospect that one day this debilitating neurodevelopmental disorder may have a viable treatment.
The CACNA1C gene’s exon 8A region is impacted by the genetic mutation that causes Timothy syndrome. Instructions for managing calcium channels, which are essential for intercellular communication within cells, are encoded in the gene. There is another region (exon 8) in the human CACNA1C gene that regulates calcium channels; this region is unaffected in Timothy syndrome type 1. The study’s ASOs restored normal calcium channel functioning by lessening the usage of the mutated exon 8A and increasing reliance on the unaffected exon 8.
MH115012, MH119319 grants.
About the National Institute of Mental Health (NIMH): The NIMH’s goal is to use basic and clinical research to transform our knowledge of mental illnesses and how they are treated, opening the door to prevention, recovery, and cure. Visit the NIMH website for additional details.
About the National Institutes of Health (NIH): The U.S. Department of Health and Human Services (HHS) is home to 27 Institutes and Centers that conduct medical research nationwide. S. Administration for Health and Human Services. The National Institutes of Health (NIH) is the main federal organization that funds basic, clinical, and translational medical research. It also looks into the causes, effects, and solutions of both common and uncommon diseases. Go to www.nih.gov to learn more about NIH and its initiatives.
