Jun 10th 2015

Three things we have to crack before we can find any cures for Alzheimer's


"A new drug called Aducanumab is showing promising signs in early human trials. Lets hope for more."

The Conversation

An estimated 36m people worldwide suffer from dementia. Alzheimer’s disease is the biggest cause, but the treatments available are inadequate only improving some of the symptoms. In the decade between 2002 and 2012 there were 244 drugs trialled in patients yet just one of these trials resulted in a drug being approved for treatment – a failure rate of 99.6%.

This sustained failure makes investing money in these expensive trials very risky, and has led to a number of pharmaceutical companies stopping or reducing research in these areas. Due to increased life expectancy, particularly in developing countries the number of cases of dementia is predicted to triple by 2050. Dementia is already the leading cause of death of women in the UK and the fifth highest cause of death in men.

The lack of treatments, devastating impact and economic burden that dementia places on society makes developing effective treatments one of our most urgent unmet clinical needs. There are often sensationalised reports in the media claiming that we have discovered a cure for dementia, but why have these discoveries not led to an actual benefit for patients?

Finding it long before the signs

We first notice Alzheimer’s when patients begin to develop memory impairments and other cognitive problems, however the disease processes is thought to begin decades before. Because Alzheimer’s disease occurs over such a long period of time, it makes studying the disease both difficult and expensive.

Despite these difficulties significant progress has been made in identifying genetic and environmental factors that increase the risk of developing Alzheimer’s disease. This in turn has generated targets for new drugs, such as factors in the immune system or proteins in the brain, but patience is needed as the process of developing new drugs is a long and costly one. 

Unfortunately by the time clinical symptoms of Alzheimer’s disease happen, the patient has already suffered significant brain damage. So an explanation for the failure of so many trials is that we are treating too late in the disease, and that these drugs may actually have been successful if given earlier on. This is a problem as currently the only way to confirm the diagnosis of Alzheimer’s disease is by looking at the brain after death, which means identifying patients early for drug trials is very challenging.

It has been shown that a significant number of patients enrolled on drug trials did not actually have Alzheimer’s disease. This is a huge issue as those patients would never have responded to the treatments, and it makes it much harder to detect any beneficial effects of the drug. New research is allowing more certain diagnosis of Alzheimer’s disease, however early and reliable diagnosis is still a long way off.

Moving animal research to humans

Animals such as mice and rats are used to model Alzheimer’s disease and to test new drugs on. Many drugs work fantastically well in these animal models, but are ineffective in humans. This is due to differences between the models and the human disease, and representing Alzheimer’s disease in the lab is actually very challenging. This is partly because we do not understand the disease process, but it also comes down to time. Alzheimer’s disease develops over decades, yet the average lifespan of a mouse is a couple of years. This makes it impossible to represent one of the most important aspects of the disease – ageing.

A focus on funding

The economic cost of Alzheimer’s disease and other causes of dementia is higher than that of cancer, in the UK it is thought to cost cost the UK economy about £26 billion a year, around £10 billion more than cancer. However ten times less money is spent researching dementia than cancer.

The prime minister committed to doubling funding for dementia research by 2025. Although this still leaves dementia significantly behind, increasing funding – and therefore the number of scientists working in this area – will help to improve our understanding of dementia and will enable earlier diagnosis and better modelling of Alzheimer’s disease in the lab. A new drug called Aducanumab is showing promising signs in early human trials. Lets hope for more.

The Conversation


This article was originally published on The Conversation. Read the original article.

Browse articles by author

More Essays

Jan 23rd 2021
EXTRACT: "The ageing global population is the greatest challenge faced by 21st-century healthcare systems. Even COVID-19 is, in a sense, a disease of ageing. The risk of death from the virus roughly doubles for every nine years of life, a pattern that is almost identical to a host of other illnesses. But why are old people vulnerable to so many different things? It turns out that a major hallmark of the ageing process in many mammals is inflammation. By that, I don’t mean intense local response we typically associate with an infected wound, but a low grade, grinding, inflammatory background noise that grows louder the longer we live. This “inflammaging” has been shown to contribute to the development of atherosclerosis (the buildup of fat in arteries), diabetes, high blood pressure , frailty, cancer and cognitive decline."
Jan 20th 2021
EXTRACT: "Anthropos is Greek for human.... The term is used to convey how, for the first time in history, the Earth is being transformed by one species – homo sapiens. ...... The idea of the Anthropocene can seem overwhelming and can generate anxiety and fear. It can be hard to see past notions of imminent apocalypse or technological salvation. Both, in a sense, are equally paralysing – requiring us to do nothing. .. I consider the Anthropocene as an invitation to think differently about human relationships with nature and other species. Evidence suggests this reorientation is already happening and there are grounds for optimism."
Jan 7th 2021
EXTRACT: "During the second world war, Nazi Germany banned all listening to foreign radio stations. Germans who overlooked their duty to ignore foreign broadcasts faced penalties ranging from imprisonment to execution. The British government imposed no comparable ban which would have been incompatible with the principles for which it had gone to war. That’s not to say, though, that it wasn’t alarmed by the popularity of German stations. Most effective among the Nazis broadcasting to the UK was William Joyce. This Irish-American fascist, known in Britain as “Lord Haw-Haw”, won a large audience during the “phoney war” in 1939 and early 1940, with his trademark call sign delivered in his unmistakable accent: 'Jairmany calling, Jairmany calling'. "
Jan 6th 2021
EXTRACTS: "The revelation of Trump’s hour-long recorded call with Brad Raffensperger, Georgia’s Secretary of State, over this past weekend crossed a new line – a line that not only set a high-water mark of moral reprehensibility, but a legal line as well, specifically in his pressuring Raffensperger to 'find the 11,780 votes' that would hand Trump the state and his veiled threat (' it’s going to be very costly…') if Raffensperger failed to comply. ........ Raffensperger – who has been forced to endure intense pressure, intimidation and threats – has proven himself to be a man of integrity and principle."
Jan 6th 2021
EXTRACT: "A final, perhaps more sinister, possibility is that Johnson knows exactly what he is doing. His political style evokes a unique blend of dishevelled buffoon and privileged Etonian. He is someone who likes to bring good news and doesn’t take life too seriously. Making tough, controversial decisions threatens this persona and so hiding in the shadows until his hand is forced helps him to reconcile his identity threat."
Dec 21st 2020
EXTRACT: "The resultant loss of land, the growing impoverishment of its citizens, and the hostile actions of Israeli occupation forces and settlers have forced many Bethlehemites to leave their beloved city and homeland. Given these accumulated violations of human rights and their impact on Christians and Muslims, alike, one might expect Christians in the West to speak out in defense of these residents of the little town they celebrate each year.  That, sadly, is not to be – most especially (and I might add ironically) among powerful Christian conservative groups in the US which, after all, claim to be the defenders of their co-religionists world-wide."
Dec 7th 2020
EXTRACT: "Worldwide, people donate hundreds of billions of dollars to charity. In the United States alone, charitable donations amounted to about $450 billion last year. As 2020 draws to a close, perhaps you or members of your family are considering giving to charity. But there are, literally, millions of charities. Which should you choose?"
Dec 1st 2020
EXTRACT: " The Museum of Modern Art is currently presenting Félix Fénéon: The Anarchist and the Avant-Garde – From Signac to Matisse and Beyond, examining the immense influence of this art critic, editor, publisher, collector and anarchist............A crucial feature of anarchism is the emphasis on the individual as the fundamental building block, the essential point of departure for any human association whatever. The individual was characterized by Grave in 1899 as a social creature who should be “left free to attach himself according to his tendencies, his affinities, free to seek out those with him whom his liberty and aptitudes can agree.” "
Nov 25th 2020
EXTRACT: "As the pandemic raged in April, churchgoers in Ohio defied warnings not to congregate. Some argued that their religion conferred them immunity from COVID-19. In one memorable CNN clip, a woman insisted she would not catch the virus because she was “covered in Jesus’ blood”. "
Nov 18th 2020
EXTRACT: "Here are just a few ways exercise changes the structure of our brain."
Nov 15th 2020
EXTRACT: "Perhaps it is Piller’s discovery that when it comes to war there is no such thing as innocence...."
Nov 4th 2020
EXTRACT: "I imagined America as the land of the free that gave voice to the forgotten. Where race, color, and creed do not matter and human rights are guarded with zeal. Where the ingathering of all cultures and people made it richer and human resources and talent knew no limits or constraints. Where opportunity awaits the able and generosity is extended to the needy. Where everyone is equal before the law and political differences are valued to make America better. Where sacrifices are willingly made to right the wrong morals and fortitude guide its leaders. Where caring about friends and allies is the hallmark of the nation and opposing oppression near and far is the emblem that distinguished America. This is the character of America. This is the soul of America. This is what made America great. The America that gave me a home. The America that fulfilled my dreams."
Oct 15th 2020
EXTRACT: "“The paintings which I propose to do will depict the struggles of a people to create a nation and their attempt to build a democracy” – this is how Jacob Lawrence described his project in 1954. Over sixty-five years later his proposal has, if anything, become only more urgent. Two days after this exhibition closes, Americans will vote in what is arguably the most significant election in a generation, an election that will measure our commitment to preserving that democracy, the struggle for which was Lawrence’s mighty theme."
Oct 15th 2020
EXTRACT: "There are also other ways our life stories can be passed down through generations, besides being inscribed in our DNA...... One 2014 study looked at epigenetic changes in mice. Mice love the sweet smell of cherries, so when a waft reaches their nose, a pleasure zone in the brain lights up, motivating them to scurry around and hunt out the treat.... The researchers decided to pair this smell with a mild electric shock, and the mice quickly learned to freeze in anticipation....... The study found this new memory was transmitted across the generations. The mice’s grandchildren were fearful of cherries, despite not having experienced the electric shocks themselves. The grandfather’s sperm DNA changed its shape, leaving a blueprint of the experience entwined in the genes."
Oct 1st 2020
EXTRACT: "As we Americans face the potential loss of a peaceful transition of power after the election and the possible end of democracy as we know it, we are reminded that discourse matters, that words matter and that the one who quotes poetry is a man who reads—and that matters."
Sep 25th 2020
EXTRACT: "We now know the potentially appalling long-term effects of suffering cruelty from others, including damage to both physical and mental health. The benefits of being compassionate towards oneself, rather than treating oneself cruelly, are also increasingly recognised..... And the idea that we must suffer to grow is questionable. Positive life events, such as falling in love, having children and achieving cherished goals can lead to growth..... Teaching through cruelty invites abuses of power and selfish sadism. Yet Buddhism offers an alternative - wrathful compassion. Here, we act from love to confront others to protect them from their greed, hatred and fear. Life can be cruel, truth can be cruel, but we can choose not to be."
Sep 19th 2020
EXTRACT: "Over his incredible career, David Attenborough has seen more of earth’s natural wonders than almost anyone. To hear him talk, with such clarity, about how bad things are getting is deeply moving. Scientists have recently demonstrated what would be needed to bend the curve on biodiversity loss. As Attenborough says in the final scene, “What happens next, is up to every one of us”. "
Sep 15th 2020
EXTRACTS: "The Anglo-Australian multinational company Rio Tinto – the largest iron ore mining company in the world – demolished two 46,000-year-old Aboriginal rock shelters in May.......The Dampier Archipelago of Western Australia is home to thousands of Aboriginal pictographs, and perhaps the oldest surviving rock art in the world. Indeed, Australia’s Indigenous art represents the longest uninterrupted tradition of art in the world – going back over 50,000 years......Aboriginal people represent the oldest continuous culture in the world...."