CAMBRIDGE, Mass.--(BUSINESS WIRE)--Triplet Therapeutics, Inc., a biotechnology company leveraging human genetic insights that identified the DNA damage response (DDR) pathway as a basis for novel treatments for repeat expansion disorders, today announced it has initiated a natural history study of Huntington’s disease (HD) to assess clinical outcomes and biomarkers that will inform upcoming interventional clinical trials. The study, called SHIELD HD, enrolled its first patients last week in Toronto, Canada.
“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, M.D., Ph.D., Triplet’s chief medical officer. “The more we understand, the closer we can get to developing therapies that prevent or delay symptom onset and halt or slow progression. We are so grateful to the patients, families, and clinicians who are participating in the study and advancing our understanding and treatment options.” Dr. Antonijevic, who was named CMO in March, is an expert in neuroscience drug development who was previously Medical Director at CHDI, a leading HD research foundation, and vice president of translational medicine and development at Wave Life Sciences.
SHIELD HD is a prospective, longitudinal natural history study that will enroll approximately 60 HD gene expansion carriers and follow them for up to two years at clinical sites in North America and Europe. The study will assess a range of clinical outcomes and biomarkers including cognitive, motor, and functional measures such as the composite Unified HD Rating Scale (“cUHDRS”), brain MRI data, DDR gene expression, and the blood and spinal fluid biomarker known as neurofilament light chain. SHIELD HD results will augment data from upcoming clinical trials and inform their interpretation.
The study includes both early manifest and premanifest individuals, enriched for premanifest individuals who have begun to show signs or symptoms. The duration of SHIELD HD is designed to observe a rate of decline in key clinical outcomes that is clinically meaningful.
The first patients to participate in SHIELD HD were screened in the last two weeks in the clinic of Mark Guttman, MD, at the Centre for Movement Disorders at the University of Toronto. Dr. Guttman has published extensively on HD, including studies of biomarkers and symptoms characteristic of early manifest and premanifest disease.
“We are at the beginning of a new era in treating neurodegenerative repeat expansion disorders, with research on HD leading the way,” said Dr. Guttman. “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.”
Triplet is pursuing a transformative approach to developing treatments for HD and other repeat expansion disorders, a group of more than 50 known genetic diseases associated with expanded DNA nucleotide repeats. A significant body of human genetic evidence has revealed the DDR pathway’s role as a potential unifying mechanistic pathway that drives onset and progression across a wide range of these debilitating disorders.
To precisely reduce activity of select DDR targets, Triplet is developing antisense oligonucleotide (ASO) and small interfering RNA (siRNA) development candidates designed to prevent or delay disease onset and stop or slow disease progression, selecting the appropriate modality based on the specific disease. The approach targets the fundamental driver of disease, operating upstream of other approaches currently in development.
“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, Ph.D., Triplet’s chief executive officer, president, 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.”
Triplet’s Scientific Advisory Board includes several world-leading authorities on HD, including Sarah Tabrizi, neurologist and Ph.D., professor of clinical neurology at University College London, and Jim Gusella, Ph.D., 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 Dr. Tabrizi. “We owe it to patients to make that happen as quickly as possible.”
Dr. Gusella, whose pioneering work since the 1980s helped establish the genetic cause of HD and more recently identified genetic modifiers of the disorder, said he was excited to see Triplet laying a strong foundation for clinical trials. “We are moving quickly,” he said. “I have been studying HD for decades, and there has never been a more exciting time than this one.”
HD is a genetic disorder linked to a mutation in the HTT gene characterized by an increase in the number of CAG repeats within the gene. The presence of these repeats, beyond a certain threshold, wreaks havoc on brain function, affecting mood, cognition and motor skills, ultimately leading to death. Thanks to the contributions of thousands of patients – whose participation in genetic research has built a fundamentally new understanding of the cause of repeat expansion disorders – it is now known that the number of repeat sequences expand over time in patients, increasing the toxic impact on cells, particularly neurons. The DDR pathway plays a central role in driving this process.
About Triplet Therapeutics
Triplet Therapeutics is a biotechnology company developing transformational treatments for patients with unmet medical needs leveraging insights from human genetics to target the underlying cause of repeat expansion disorders, a group of more than 50 known genetic diseases including HD, myotonic dystrophy, spinocerebellar ataxias and fragile X syndrome. Triplet was founded by Nessan Bermingham, Ph.D., Atlas Venture, and Andrew Fraley, Ph.D. Triplet is backed by investments from Atlas Venture, MPM Capital and Pfizer Ventures, along with Invus, Partners Innovation Fund and Alexandria Venture Investments. Triplet is headquartered in Cambridge, Mass. For more information, please visit www.triplettx.com.