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Brain cells from skin
LONDON—Dr. Selina Wray overcame stiff competition from three other research teams to win three years of funding to develop an innovative new way to screen potential new treatments for diseases such as Alzheimer’s. The announcement came during a week she was also named Pioneer of the Year for her research achievements in Red Magazine, a U.K. women’s-oriented publication.
“It’s an honor to have been singled out as a female pioneer for my research, and highlights just how much dementia is at the forefront of public consciousness,” said Wray, who is an Alzheimer’s Research Trust Research Fellow at University College London. “Now with almost a million pounds of new funding to continue my work, I hope to be able to make bigger and faster strides and play my part in the effort to defeat dementia.”
Part funded by the NIHR Queen Square Dementia Biomedical Research Unit (BRU), Wray’s work involves an innovative use of stem cells to understand what causes dementia. She has also been a dedicated advocate for increased funding of dementia research and attended the recent Global Dementia Legacy Event hosted by Prime Minister David Cameron and Secretary of State for Health Jeremy Hunt.
“It’s really great to have this recognition for our work into a condition that affects so many of us, whether directly or through seeing family and friends affected by the disease. The U.K. has led the way with many research breakthroughs and also with the prioritization of dementia research through the prime minister’s Dementia Challenge, and I’m proud to be a part of that both as a scientist and as an advocate,” Wray said.
With current dementia treatments only helping with symptoms for a limited time, there is a desperate need for effective new treatments that can slow or stop diseases like Alzheimer’s. Last year, scientists were challenged to use the latest stem cell techniques to pioneer a cell model of dementia in the lab to be used for drug screening. The challenge, called CRACK IT UnTangle, is led by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) and co-sponsored by Alzheimer’s Research UK, Eli Lilly and Janssen.
The discovery that pathogenic mutations in the microtubule associated protein tau (MAPT) gene can cause a familial neurodegenerative tauopathy has provided compelling evidence that tau dysfunction is sufficient to cause neurodegeneration. Many recent in-vivo studies have shown that tau aggregates have “prion-like” properties that not only allow them to transmit or seed further tau aggregation, but also spread to neighboring cells or functionally connected brain regions. This process is referred to as “tau propagation” and might explain the stereotypic progression of tau pathology in the brains of Alzheimer’s disease patients.
Study of the development and spread of tau pathology in animal models requires large numbers, is time-consuming and expensive. Often, the mechanisms and/or potential drug targets that are identified do not translate into humans.
The first phase of the challenge saw four initial teams awarded £100,000 for six months to see who could develop the most promising way to recreate the buildup of the hallmark dementia protein tau in cells in the laboratory. Three teams reapplied for the full £900,000 (about $1.47 million) award, with London-based Wray and colleagues at the University of Strathclyde awarded the top prize.
During the first six months of the project, the team showed they could effectively transform patient skin cells into nerve cells in the lab, which grew connections and communicated with each other. The nerve cells also developed a build-up of tau protein, similar to that seen in the brains of people with Alzheimer’s and frontotemporal dementia. The team will now work with Edinburgh-based companies RBiomedical and Roslin Cells to scale up their experiment to improve drug discovery for these devastating diseases.
Wray noted that “While dementia research has been in the shadows for many years, we’re starting to see growing efforts to coordinate research towards a cure. One important step in developing effective treatments for dementia is to recreate aspects of diseases that cause it in the laboratory. We’re using skin cells taken from people with dementia and turning them into working nerve cells in a dish. Now that we’ve shown our cells recreate the build-up of tau seen in the brain, we can start to scale this up so it can be used to screen for drugs that could stop tau in its tracks.”
Dr. Simon Ridley, head of research at Alzheimer’s Research UK, said: “The tau protein is thought to be a key player in diseases like Alzheimer’s and is a promising target for new dementia treatments. To develop drugs with the best chance of success, we must develop robust ways to test them in the lab. This funding recognizes the innovation shown by the team in addressing this problem, and we hope their solution will make big strides in drug discovery for dementia.”
As for her recognition as part of Red Magazine’s Women of the Year awards, Wray was recognized for the importance of her work and her dedication to exploring innovative new ways to transform the search for new dementia treatments, and she received the award at a ceremony in London.