果冻影院

Her breakthroughs have, and continue to, push the field forward at pace and bring real hope to those affected by this heart-breaking neurodegenerative disorder. For her outstanding efforts and achievements, Professor Tabrizi is recognised with this year鈥檚 prestigious MRC Millennium Medal.

搁别蹿濒别肠迟颈苍驳听on her career to date, passion for scientific investigation and tireless drive to deliver a cure for her patients, Professor Tabrizi (果冻影院 Queen Square Institute of Neurology) said: "I really loved medicine and I became very excited about neuroscience. Edinburgh鈥檚 medical department was quite old school and in the second year you literally spent a year dissecting a human brain.鈥�

Professor Tabrizi first encountered Huntington鈥檚 disease during her MRC Clinical Training Fellowship PhD at 果冻影院 studying mitochondrial dysfunction in neurodegeneration, when supervisor Professor Tony Schapira (果冻影院 Queen Square Institute of Neurology) took her to a nursing home to collect skin biopsies from people living with disease.

She said: 鈥淚 met many patients and families at that time, and they all had advanced disease. It really struck me the way the disease affected young people, because these were people who were in their 20s, 30s and 40s with end-stage disease, still able to interact and recognise me. It was very moving.鈥�

Huntington鈥檚 disease is caused by the build-up of the mutant huntingtin protein in neurons. This leads to progressive cellular death, manifesting as a devastating worsening of coordination, involuntary body movements and mental ability. In most cases, it is inherited, and a child of an affected person will have a 50% risk of developing the condition.

Upon becoming a full professor in 2009, Professor Tabrizi听took the decision to dedicate all her efforts to studying and finding much-needed treatments for the disease. With her former PhD co-supervisor and long-time collaborator Professor Gill Bates (UK Dementia Research Institute at 果冻影院 & 果冻影院 Queen Square Institute of Neurology), she established the 果冻影院 Huntington鈥檚 Disease (HD) Centre in 2016. Although scientific curiosity led Professor Tabrizi听into the field, it鈥檚 now the hope of those she cares for that drives her work.

Professor Tabrizi said:听鈥淚 have looked after generations of patients and families from 1997 when I started doing clinics, and sadly all of them have died. I've looked after people in their teens and 20s. Fathers and sons, mothers who have lost their husband and three听children to the disease. And I鈥檝e got to know them very well. I am absolutely passionate and committed to finding a treatment for Huntington's disease. I really do feel like it's my life's work and I focus on it to the exclusion of lots of things. I realised that focus is the most important thing for me.鈥�

As a clinical neuroscientist, that motivation pushed Professor Tabrizi听to publish over 350 scientific publications and drive multiple pioneering projects to transform the Huntington鈥檚 disease field. This includes our understanding of the underlying biology, how we predict, monitor and measure disease, when best to intervene and how to optimally run clinical trials. Professor Tabrizi听was also responsible for designing and running the ground-breaking global phase I/IIa trial of IONIS Pharmaceutical鈥檚 antisense oligonucleotide (ASO) therapy, whose results made headline news in late 2017 for delivering the first demonstration of antisense-mediated suppression of a toxic protein in adults with a neurodegenerative disease.

For Professor Tabrizi, collaboration is at the heart of this progress, and critically contributes to both her development and that of the field.

She said: 鈥淎ll of my work over the years has been really collaborative. I have a close community both at the HD Centre with Professor Gill Bates, Professor Ed Wild and Dr Rachael Scahill (all 果冻影院 Queen Square Institute of Neurology), many others at 果冻影院 Queen Square Institute of Neurology, and a global network worldwide. That's why I really suffered in the pandemic because I really missed the travelling and interaction with every one of my colleagues. So I'm a big fan of collaboration and I see it as the only way that we鈥檒l be able to find treatments for these diseases. It's definitely not a one-person race.鈥�

It is not just interactions with her established peers that Professor Tabrizi听values, from working for Professor David Marsden and Professor Anita Harding at 果冻影院 Queen Square Insitute of Neurology听in 1994, who pioneered the fields of movement disorders and neurogenetics respectively, to linking up with researchers working on exciting new avenues such as DNA repair expert Dr Gabriel Balmus (UK DRI at Cambridge), but also her mentorship of the next generation of scientists continuing this vital work.

Over the past 16 years, she has successfully brought through 33 PhD students, including 17 clinicians. Having worked her way to the top in a predominantly white male field, equality, diversity and inclusion are also an upmost priority to Professor Tabrizi. As with her research, she leads from the front.

Professor Tabrizi explained: 鈥淚'm really keen to encourage diversity. I think when you're brought up being the child of a first-generation immigrant, you see the kind of difficulties your parents have faced. I've also been very involved with the Academy Medical Sciences鈥� mentoring program, Sustain, for young women scientists. I've helped solve quite a few big issues because these are all things that I've experienced, and then managed to get support myself to get through.

One of the most important skills Professor Tabrizi听is keen to press on her mentees is their relationship with failure.

She said:听鈥淚 don't know anyone who hasn't failed at some point. It鈥檚 important to learn resilience because when I was doing my first postdoc with Charles Weissmann, a brilliant scientist, I sent off a paper containing some great data, I thought.听One of the reviewers came back and wrote, 'If this had been submitted 20 years ago, it would have been exciting',听and I was听really upset. At that point Charles told me I would need to grow a thicker skin to survive science.鈥�

No more acutely has this type of disappointment been felt than when the Phase III trials of the pioneering ASO therapy for Huntington鈥檚 disease were abruptly stopped in March 2021, as patients in the treatment group were progressing worse than their placebo counterparts.

Despite this setback, Professor Tabrizi听remained hopeful and keen to squeeze every bit of knowledge gained from that failure to ensure better, safer trials. Future trials will also benefit from her听other pioneering developments including biomarker safety data and the recently developed four-stage Huntington鈥檚 disease staging system for defining disease progression, similar to that which has revolutionised the cancer field. This will facilitate clinical trials decades before clinical onset.

It is perhaps the most tragic aspect of Huntington鈥檚 disease, that defines the greatest strength of the community around it. As Professor Tabrizi听explains:听鈥淎 parent, children, siblings, grandchildren can be affected... It is a disease of families. For everyone who works in the听field, some even with the mutant gene themselves, we often feel like we're part of the Huntington鈥檚 family, and the patients are very much part of that.鈥�

It鈥檚 through her various roles - researcher, mentor, colleague, director, spokesperson, advocate, triallist, clinician 鈥� and the care Professor Tabrizi听takes in performing them, that she听inspires and pulls this family together.

And on remaining focused and delivering those desperately needed treatments, she said:听鈥淚'm not going to give up. I'm very tenacious. Like a dog with a bone!鈥�

Links

• 果冻影院 Queen Square Institute of Neurology
• 果冻影院 Brain Sciences

Images

(From top)

• Professor Sarah Tabrizi
• Professor Sarah Tabrizi receiving a donation from patients and their families
• Professor Sarah Tabrizi with colleagues at the 果冻影院 Huntington鈥檚 Disease Centre in 2017

Media contact听

Alex Collcutt

UK DRI, Research Communications Manager