The University of Aberdeen, led by Zosia Miedzybrodzka, cares for Huntington’s disease (HD) patients, such as Sandy Patience of Scotland, as the 801 patient global study known as Generation-HD1 unfolds. Patience inherited this condition and declared the clinical program was taking him from a “real place of darkness.” Can this experimental gene blocking compound, sponsored by Roche, slow the progression of this deadly inherited disease? This patient and his family have faced a shattering reality; participating in this global clinical trial has positively impacted his life to the point now for a mission, a cause, and a ‘focus for the good.’
The Irish News recently reported about Sandy Patience, a patient participating in a gene therapy clinical trial at the University of Aberdeen in Scotland. Mr. Patience, originally residing from Avoch in the Highlands, was diagnosed with this inherited condition two years ago. The disease stops the brain from properly functioning over time. Patients start to struggle with problems ranging from memory difficulties and psychiatric issues, to uncontrolled movements—most often fatal within 20 years once it becomes obvious. There is no cure, nor effective treatments.
A Patient’s and a Family’s Devastating Reality
Patience, a railroad signalman, lost his mom to the disease when she was 59. He told the Irish-based press that although he was 21 when she passed, “I never really knew her well, as the disease took so much from her.” Childhood was difficult and far from normal. As a young lad, he spent days not playing football with kids, but visiting hospital rooms to visit relatives hit by this devastating inherited disease. A disease that knows no mercy, striking his sister as well with a steady deterioration as she fades away in a rest home. Sandy was quoted, “Huntington’s has robbed her of everything, apart from her wonderful wit and a determination to keep going.” Where could hope be found? Patience learned of a clinical trial and an experimental therapy.
Sandy became a patient in the Generation-HD1 study which evaluates the efficacy, safety, and biomarker effects of Roche’s investigational RO7234292 (RG6042) compared with placebo in patients with manifest Huntington’s disease (HD). Sandy Patience heard of the trial and compelled himself to participate. RG6042, a Phase III clinical trial, gauges the potential of gene-silencing approaches for HD and other diseases. RG6042 is an antisense oligonucleotide (ASO) that originates with Ionis.
Also known as ONIS-HTTRx, the drug was designed to reduce the production of huntingtin (HTT) protein, which is the genetic cause of HD. HD is triggered by the expansion of the CAG trinucleotide sequence in the HTT gene, which produces a toxic protein that progressively destroys neurons in the brain. Consequently, HD patients face a devastating and progressive loss of mental faculties and physical control as their disease progresses. Dr. Jeff Carroll of HDBuzz summarized the study in March 2019.
Sandy Patience participates with the University of Aberdeen site, one of 11 such sites in the UK, reports the Irish Press. The worldwide clinical trial involves 15 countries and includes 101 such sites. Mr. Patience must travel from his residence in Inverness to Aberdeen Royal Infirmary, where brain fluid samples are collected and analyzed, and thereafter, the trial drug or placebo is administered. The study runs till August 2022.
Roche & Ionis Partnership
Roche and Ionis (formally Isis Pharmaceuticals of San Diego) allied in 2013 to develop treatments for HD based on their ASO platform. The drug is a short strand of genetic code that binds to the mutant Huntington gene product (mHTT). Previous studies have shown the experimental therapy to be well-tolerated, and evidence potential to provide disease-modifying benefits to patients with neurodegenerative diseases, including HD. By combining the antisense expertise of Ionis and Roche’s background in developing neurodegenerative therapeutics, the two sought to combine the ASO and Roche’s “brain shuttle” program to treat diseases such as HD. The hope is that this experimental treatment will lower mHTT levels in the brain and possibly slow down the HD progression.
The Investigational Site
The University of Aberdeen, Institute of Medical Sciences (the flagship research institution of the university) represents a thriving community of researchers and support staff working on cutting-edge biomedical subjects aimed at understanding how the human body functions. They are the largest research center at the university with 411 research and support staff—inclusive of 84 principal investigators, 106 post-doctoral scientists and academics, 75 technicians, and 140 PhD students. In the last year, the staff has raised £30 million in research funding while publishing over 415 peer-reviewed papers.
A New Inspired Mission
Patience reported to the press that although he looks at bleak odds, participating in this study has offered hope and inspiration, and that a new and positive outlook has emerged. Rather than facing this life and reality “from a place of darkness,” he now chooses “to focus on the good.” He feels he could “write a book about the illness and its effects, but right now, I’m too busy living.”
Professor Zofia Miedzybrodzka, MB ChB, PhD, FRCP Edin, FRCOG
Professor Miedzybrodkzka of Medical Genetics at the University of Aberdeen. She is also an honorary consultant clinical geneticist and Service Clinical Director of Genetics for NHS Grampian (comprising Clinical Services and diagnostic DNA and cytogenetics laboratories), and co-director of the University of Aberdeen Centre for Genome-enabled Biology and Medicine.
Call to Action: Are you based in Scotland and have HD in the family? The National Care Framework for Huntington’s Disease offers resources and information.