First groundbreaking, gene therapy in clinical trials slowed the progression of Huntington’s disease, a rare genetic disorder in which toxic bits of proteins malfunction and death.
Previously, approved treatments for Huntington’s disease have been aimed at managing the symptoms. This most often appears in a person’s 30s or 40s. Progressive states injure and kill important neurons involved in controlling mood, cognition, and motor control. Various drugs help offset depression, hallucinations, and inadequately regulated movements that result from their destruction.
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Now in the trial results shared on Wednesday (September 24), scientists have announced that a new gene therapy called AMT-130 appears to slow the progression of the disease.
“These groundbreaking data are the most compelling evidence in the field to date, highlighting the disease-correcting effect of Huntington’s disease, where urgent needs persist,” said Dr. Sarah Tabrizi, the leading scientific advisor to the trial and lead scientific advisor at the Huntington’s Disease Centre at the University of London (UCL) (UCL) in a statement. “For patients, the AMT-130 can maintain daily functioning, keep them at work longer and slow the progression of the disease significantly.”
Huntington’s disease, estimated to affect about 1 in 20,000 to 10,000 people in the United States, is caused by a mutation in a gene called HTT and is directed by a protein known as huntitin. Protein is found in many tissues throughout the body, but its volume is the highest in the brain. The role of proteins in cells is not fully understood, but its proposed work involves repairing damage to DNA and transporting material within the cell.
There is a part of the HTT gene, and the three letters (CAG) of its DNA code are repeated approximately 10 to 35 times depending on the person. However, in people with Huntington’s disease, the repetition becomes extreme, with CAG displayed more than 36 to 120 times. People with repetition levels of 40 or more almost always develop the disease, while those between 36 and 39 are at a lower risk. Repeatedness causes cells to create an overlong version of the huntitin protein and break down into smaller, toxic fragments that accumulate within brain cells.
Developed by trial sponsor Uniqure, gene therapy AMT-130 works by silencing the HTT gene. In particular, gene therapy is usually not 100% efficient. In other words, treatment does not affect all copies of HTT within the target tissue. Therefore, rather than eliminating the activity of the gene, it significantly lowers it.
To that end, the treatment introduces new genes into cells in two parts of the brain that are hard hit by the Huntington nucleus and the caudate nucleus. The gene itself contains the instructions of microRNA, a type of molecule that regulates gene activity. In this case, MicroRNA derails the process by which the code for the HTT gene is translated into proteins. Latches into messenger RNA (mRNA) within the cell. This usually relays the HTT blueprint to the protein construction factory within the cell.
AMT-130 therapy is delivered into the body within the harmless virus, which acts as a delivery truck for MicroRNAs. (These types of viruses are commonly used in gene therapy.) Treatment of the brain requires complicated surgery, during which time doctors use MRI to direct small catheters to the correct spots of the organ. Treatment is given in one dose, so only one surgery is required to do so.
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In the trial, 29 patients received the new treatment, 17 got the higher doses and 12 got the lower doses. Twelve patients from each group were subsequently followed for three years of follow-up, which was included in this new analysis.
Treated patients received only standard care and were compared to a cohort of people in Huntington who were followed in a longitudinal study called Enroll-HD. Trial runners followed patients, followed patients and compared them with one another using standard rating scales for the progression of Huntington’s disease. We also measured patients’ levels of neurofilament photoprotein (NFL) that appear in the fluid surrounding the spinal cord when neurons are damaged.
The results of the trial showed that at the 3-year mark, patients receiving a high dose of AMT-130 had 75% less disease progression compared to cohorts given standard treatment. The high-dose group also showed a decrease in mean NFL levels over that time frame, suggesting a decrease in the magnitude of nerve damage. Protein levels usually skyrocket by about 20% to 30% over three years.
“AMT-130 is generally well tolerated and has a manageable safety profile at both doses,” the statement said. “Most common adverse events [side effects] The treatment group was all related to the resolved administration procedure. ”
“My patients during the exam have stabilized over time. “One of them is my only medically retired Huntington’s disease patient who has been able to return to work,” Dr. Ed Wild, the lead investigator at the UCL Huntington’s Disease Center’s testing site, said in a statement.
He said, “The results of the test arrive in numbers and graphs, but behind each data point is an incredible patient volunteering to undergo a major neurosurgery that will be treated with the first gene therapy ever tested for Huntington’s disease.
The company is expected to submit an application for approval to the US Food and Drug Administration (FDA) early next year, with European applications expected to continue. The AMT-130 has already been granted a groundbreaking therapy designation by the US FDA and a highly regenerative medicine treatment designation. Both find very promising that modulators treat patients with unmet medical needs.
This article is for informational purposes only and is not intended to provide medical advice.
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