Natural History Study of Huntington’s Starts Enrolling Participants
The first patients have been enrolled in a clinical study of the natural history of Huntington’s disease (HD) and its biomarkers, to better inform how to measure and monitor early signs of the disease and support future clinical studies.
The SHIELD HD study, sponsored and led by Triplet Therapeutics, will enroll participants across clinical sites in North America and Europe. Currently, the Centre for Movement Disorders in Toronto, Canada, is actively recruiting, and has already screened and enrolled the first patients for the study.
“SHIELD HD will help us better understand how to measure and monitor early signs of the disease and will inform future interventional trials aiming to treat the underlying cause before significant damage has occurred,” Mark Guttman, MD, a leading expert in Huntington’s disease at the Centre for Movement Disorders at the University of Toronto, said in a press release.
“We are at the beginning of a new era in treating neurodegenerative repeat expansion disorders, with research on HD leading the way,” he said.
Huntington’s is a genetic neurodegenerative disorder caused by excessive repeats (more than 35) of a portion of DNA, called CAG triplets, within the HTT gene. This leads to the production of abnormal HTT protein, which affects brain function and leads to mood changes, cognition issues, and loss of motor skills.
The natural history SHIELD HD study (NCT04406636) aims to enroll approximately 60 individuals carrying an expansion in the HTT gene. Participants with early manifest and premanifest Huntington’s will be followed for up to two years.
Throughout this period, researchers will evaluate a range of cognitive, motor, and functional clinical outcomes and disease biomarkers, including the activity of genes belonging to the DNA Damage Repair (DDR) pathway, and the levels of the neurofilament light chain (NfL) in the blood and spinal fluid.
Of note, DDR genes are thought to modulate age of onset and disease severity in Huntington’s and other neurodegenerative diseases. NfL has been proposed as a biomarker of nerve cell damage in Huntington’s and other diseases such as multiple sclerosis.
The results of this study will help inform assessments for a future interventional treatment trial.
“HD is a devastating neurodegenerative disease with limited treatment options. SHIELD HD is an important step toward a better understanding of the disease,” said Irina Antonijevic, MD, PhD, chief medical officer at Triplet. “The more we understand, the closer we can get to developing therapies that prevent or delay symptom onset and halt or slow progression.”
Triplet is developing treatments to tackle repeat expansion disorders that include more than 50 diseases, with a main focus on the DDR pathway. Triplet has shown that targeting this pathway holds therapeutic potential.
The company’s strategy is based on two gene silencing therapies, called antisense oligonucleotides and small interfering RNAs. Targeting gene candidates using this approach could prevent or delay disease onset, as well as slow disease progression.
“Large-scale human genetic studies by the academic community have revolutionized the way we identify the underlying genetic drivers of repeat expansion disorders including HD,” said Nessan Bermingham, PhD, Triplet’s president, CEO, and co-founder.
“Our targeted approach is based on results from these studies with our internal research providing insight into the central role the DDR mechanism plays in these diseases. Our approach has the potential to address a broad range of repeat disorders addressing unmet medical needs for hundreds of thousands of patients,” he added.
Triplet’s studies have the support of a Scientific Advisory Board led by world authorities on Huntington’s that include Sarah Tabrizi, PhD, clinical neurologist at University College London, and Jim Gusella, PhD, Bullard professor of neurogenetics at Harvard Medical School.
“HD is a genetic disease, so we should be able to use recent advances in precision medicine to stop it,” said Tabrizi. “We owe it to patients to make that happen as quickly as possible.”
Gusella, whose pioneer research in 1980s helped decipher the genetic cause of Huntington’s, added: “We are moving quickly. I have been studying HD for decades, and there has never been a more exciting time than this one.”