Drugmakers look to push the boundaries of old age


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Drugmakers look to push the boundaries of old age
Google's ambition to defy the limits of ageing has fired up interest in the field, drawing in drug companies who are already quietly pioneering research, despite the regulatory and clinical hurdles that remain.
In September life-science company Calico, which was set up by Google last year to investigate the ageing process, joined with U.S. drugmaker AbbVie in committing an initial $250 million apiece to developing cures for age-related diseases.
Away from the limelight, however, Switzerland's Novartis and Denmark's Novo Nordisk are already testing new roles for existing drugs, which could keep people alive for longer, as they look to cater to the ever larger numbers living into their 80s and beyond.
"Everybody now is talking about the ageing population and how to have a healthy old age," said Mads Krogsgaard Thomsen, Chief Science Officer at Novo Nordisk.
By 2020 people aged 60 and older will outnumber children younger than five for the first time in history, according to a paper published in the Lancet medical journal on Thursday.
But with greater age comes a bigger burden of disease.
At least 300 million people will suffer from diabetes by 2025, the World Health Organization estimates, while the global number of dementia sufferers is expected to triple to 135 million by 2050.
The goal is not to create some "elixir of life" pill to help people live ever longer, but rather to maximise healthy lifespan and reduce the period of end-of-life sickness and dependency.
Alex Zhavoronkov, chief executive of Baltimore-based biotech company Insilico Medicine, believes shifting healthcare spending from treatment to prevention will be central to this.
"Instead of trying to keep a person alive for another three to six months and essentially bankrupting healthcare systems, it might make sense to introduce drugs that prevent the onset of age-related diseases and ageing itself," he said.
Immune system booster
Research into anti-ageing drugs has historically received little attention from Big Pharma, given the difficulties of running clinical trials to prove such an effect.
Moreover, companies have been deterred by regulators in the United States and Europe who will only approve medicines for specific illnesses and not for something as broad as ageing, which is not in itself defined as a treatable disease.
Despite these obstacles, Novartis has completed a successful pilot trial examining its cancer drug everolimus as a potential treatment to reverse immunosenescence, or the gradual deterioration of the immune system that occurs with age and is a major cause of disease and death.
Encouraged by studies showing that the closely related drug rapamycin extended the lifespan of worms, flies and mice, Novartis looked for ways to assess whether everolimus could have a similar effect in humans.
The hurdles were high. Ageing is a gradual, decades-long process making it impractical to assess directly in clinical trials.
"For ageing you have to pick a target system that can be investigated in months or years, not decades," said Novartis's head of research Mark Fishman.
The company's work-around is to focus on immunosenescence. It gave 218 people aged over 65 a six-week course of everolimus followed by a regular flu vaccine after two weeks.
Results showed that taking the drug improved the immune system response by more than 20 percent compared to placebo, potentially opening the door to use it as a treatment to increase the efficacy of vaccines and help stave off the infections associated with old age.
While Fishman stresses the research is still early-stage, Novartis's work highlights the growing interest in ageing as a biological process that can be manipulated, treated and delayed.
Old drugs, new purpose
Given the regulatory barriers, experts believe re-purposing existing treatments in new indications will likely be the fastest way to get drugs with an anti-ageing benefit to market, since these medicines have already been proven safe.
A study published in the journal Neuropharmacology this week found lixisenatide, a drug sold as Lyxumia by Sanofi to treat type 2 diabetes, could slow nerve cell damage in mice with some of the hallmarks of Alzheimer's disease.
Other diabetes drugs may have a similar effect.
Imperial College London is currently recruiting around 200 patients with mild Alzheimer's for a study with Novo Nordisk's diabetes drug liraglutide, or Victoza.
"It would be fantastic if we were able to take a safe and simple type 2 diabetes medicine and use that in Alzheimer's," said Novo's Thomsen.
The results are due in two to three years and if there is a significant benefit to cognition Novo Nordisk would consider conducting a pivotal clinical trial, he added.
The Danish company, which is the world's biggest maker of insulin, is also working with academics at the University of Oxford, the Karolinska Institute and the University of Copenhagen on a new project looking at healthy ageing.
Its interest in the field has a scientific logic, since some of the genes that researchers are now exploring as factors in healthy ageing have links to the body's insulin pathways.

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