First in 20 years

Weekender
HEALTH
Aldo Ceresa was one of just a handful of UK patients in the trial.

THE first new treatment for Alzheimer’s disease for nearly 20 years has been approved by regulators in the United States, paving the way for its use in the United Kingdom. Aducanumab targets the underlying cause of Alzheimer’s, the most common form of dementia, rather than its symptoms. Charities have welcomed the news of a new therapy for the condition. But scientists are divided over its potential impact because of uncertainty over the trial results. At least 100,000 people in the UK with a mild form of the disease could be suitable for the drug if it were to be approved by the UK regulator. The US Food and Drug Administration (FDA) said there was “substantial evidence that aducanumab reduces amyloid beta plaques in the brain” and that this “is reasonably likely to predict important benefits to patients”. In March 2019, late-stage international trials of aducanumab, involving about 3,000 patients, were halted when analysis showed the drug, given as a monthly infusion, was not better at slowing the deterioration of memory and thinking problems than a dummy drug. But later that year, the US manufacturer Biogen analysed more data and concluded the drug did work, as long as it was given in higher doses. The company also said it significantly slowed cognitive decline. Aducanumab targets amyloid, a protein that forms abnormal clumps in the brains of people with Alzheimer’s that can damage cells and trigger dementia, including:

  • memory and thinking problems
  • communication issues
  • confusion

Aldo Ceresa, who took part in the trial, first noticed problems differentiating between left and right 10 years ago. After his diagnosis, the 68-year-old, who is originally from Glasgow and now lives in Oxfordshire, close to his family, had to give up his job as a surgeon. Ceresa took aducanumab for two years before the trial was halted – and then had to wait almost as long for another trial, at the National Hospital for Neurology and Neurosurgery, in London, to begin. “I’m quite happy to volunteer,” he says. “I really, really enjoy this journey that I’m going through – and obviously the benefits I’m getting from it, which I’m very, very grateful for.” He is convinced the drug has helped him. “I feel like I’m not quite as confused. Although it’s still there, it’s not quite as bad.  “And I’m just getting that bit more confident now.” – BBC


How to boost muscle regeneration and rebuild tissue

ONE of the many effects of aging is loss of muscle mass, which contributes to disability in older people. To counter this loss, scientists at the Salk Institute in California, are studying ways to accelerate the regeneration of muscle tissue, using a combination of molecular compounds that are commonly used in stem-cell research. In a study published on May 25, 2021, in Nature Communications, the investigators showed that using these compounds increased the regeneration of muscle cells in mice by activating the precursors of muscle cells, called myogenic progenitors. Although more work is needed before this approach can be applied in humans, the research provides insight into the underlying mechanisms related to muscle regeneration and growth and could one day help athletes as well as aging adults regenerate tissue more effectively. “Loss of these progenitors has been connected to age-related muscle degeneration,” says Salk Professor Juan Carlos Izpisua Belmonte, the paper’s senior author. “Our study uncovers specific factors that are able to accelerate muscle regeneration, as well as revealing the mechanism by which this occurred.” The compounds used in the study are often called Yamanaka factors after the Japanese scientist who discovered them. Yamanaka factors are a combination of proteins (called transcription factors) that control how DNA is copied for translation into other proteins. In lab research, they are used to convert specialized cells, like skin cells, into more stem-cell-like cells that are pluripotent, which means they have the ability to become many different types of cells.”Our laboratory previously showed that these factors can rejuvenate cells and promote tissue regeneration in live animals,” says first author Chao Wang, a postdoctoral fellow in the Izpisua Belmonte lab. “But how this happens was not previously known.” Muscle regeneration is mediated by muscle stem cells, also called satellite cells. Satellite cells are located in a niche between a layer of connective tissue (basal lamina) and muscle fibers (myofibers). In this study, the team used two different mouse models to pinpoint the muscle stem-cell-specific or niche-specific changes following addition of Yamanaka factors. They focused on younger mice to study the effects of the factors independent of age. In the myofiber-specific model, they found that adding the Yamanaka factors accelerated muscle regeneration in mice by reducing the levels of a protein called Wnt4 in the niche, which in turn activated the satellite cells. By contrast, in the satellite-cell-specific model, Yamanaka factors did not activate satellite cells and did not improve muscle regeneration, suggesting that Wnt4 plays a vital role in muscle regeneration. According to Izpisua Belmonte, who holds the Roger Guillemin Chair, the observations from this study could eventually lead to new treatments by targeting Wnt4. – Science Daily

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