Will We Ever Cure Alzheimers
Few drugs have been approved for treatment of this dementia, and none works very well. It has become one of the most intractable problems in medicine.
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By Pam Belluck
Its a rare person in America who doesnt know of someone with Alzheimers disease. The most common type of dementia, it afflicts about 44 million people worldwide, including 5.5 million in the United States.
Experts predict those numbers could triple by 2050 as the older population increases. So why is there still no effective treatment for it, and no proven way to prevent or delay its effects?
Why is there still no comprehensive understanding of what causes the disease or who is destined to develop it?
The answer, you could say, is: Its complicated. And that is certainly part of it.
For nearly two decades, researchers, funding agencies and clinical trials have largely focused on one strategy: trying to clear the brain of the clumps of beta amyloid protein that form the plaques integrally linked to the disease.
But while some drugs have reduced the accumulation of amyloid, none have yet succeeded in stopping or reversing dementia. And amyloid doesnt explain everything about Alzheimers not everyone with amyloid plaques has the disease.
But, of course, that is not the same as turning back the tide of the disease.
Possible Ipo In The Pipeline
Founded in 2013, Alzheon is a clinical-stage biotech startup based out of Framingham, Massachusetts that has raised a total of $37 million after a recent venture round of $15.8 million back in 2017. Alzheons pharmaceutical technology is based on ALZ-801, a standard oral drug thats meant to dissolve amyloid beta plaques by inhibiting the formation of its precursor. After withdrawing an IPO offer of $81 million earlier this year, there has been speculation by analysts that Alzheon will continue to lose money following the failure of ALZ-801 to yield favorable results in Phase 3 trials.
But it looks like Alzheon is pushing to refile an IPO for $40 million and will get another chance to conduct Phase 3 trials on ALZ-801. This time they plan to target a selective group of patients bearing genetic markers for a more specific subset of Alzheimers keeping their lead candidate in the game.
Immunotherapy Treatments For Curing Alzheimers
Founded in 2013, Alector has raised a total of $415 million after a $133 million Series E round led by Google Ventures that recently closed in July. The San Francisco-based startup was co-founded and currently led by veteran entrepreneur and neurobiologist Dr. Arnon Rosenthal. He previously founded South San Francisco-based Rinat Neuroscience, which was acquired by Pfizer for a cool $500 million in 2006. Alector is developing antibody drug technologies to target immune system receptors that could reduce early progression of Alzheimers, rather than simply attacking pre-existing plaques.
The recent round will push three of its antibody drug candidates into clinical trials. Two of those drug candidates are being co-funded and co-developed with large biopharma company AbbVie who has already paid Alector $200 million upfront with both companies agreeing to share global profits equally.
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We Can And Will Solve The Alzheimers Disease Epidemic
Alzheimers and health care organizations admit there there are a lot of challenges to tackle before a cure for the disease is found.
But there is certainly a great deal of confidence that one day, Alzheimers will be eliminated from existence.
It is impossible to predict whether this breakthrough is round the corner, but we are definitely making progress in the right direction, said Pickett. We now understand much more about the progression of Alzheimers disease and researchers are finding ways to identify people in the earliest stages where they have the best of developing treatments that work.
Snyder agreed, adding:
At the Alzheimers Association, we are optimistic about the future, and our urgency continues to grow. We can and will solve the Alzheimers disease epidemic.
To find out more about Alzheimers, please visit the Alzheimers Association website if in the US, or the Alzheimers Society website if in the UK.
Q: Does That Mean The Amyloid Hypothesis Is Completely Wrong
The amyloid hypothesis is that amyloid is the trigger of everything in Alzheimers. That seems now to be wrong.
New studies from the past decade tell us that amyloid is part of the story of Alzheimers disease, but its the smoke, not the fire. Weve learned that the single-gene and more common, complex forms of Alzheimers are not identical, though they do overlap.
Theres been a lot of backlash against the amyloid hypothesis lately, but in the 90s, it was the right idea. The pharmaceutical industry was right to jump on the amyloid bandwagon. And theyre now right to give it up, I think.
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The Richest 1 Percent
The disease tends to hit women the hardest, with twice as many women diagnosed compared to men. Alzheimers also tends to be more of an issue with the middle and upper classes. A study by University of Cambridge showed that Alzheimers is highly correlated to populations in wealthy, highly urbanized, highly industrialized nations with good hygiene, with some researchers speculating that the illness might be initiated by bacterial inflammation brought on by underdeveloped immune systems that havent been exposed to microorganisms found in less hygienic environments. Better start penciling in those urban slum play dates for the kids before its too late.
Q: First The Bad News Why Have All Drugs Tested In The Past Several Years Failed
In retrospect, the idea that reducing amyloid in the brainwhich all the failed drugs dois based on an incomplete picture of the disease.
To treat a disease, we need to treat whats broken. But its very difficult to find whats broken in these slowly progressive brain disorders.
One way to find whats broken is through genetics, but the first wave of genetic studies in the 80s and 90s only had the technical capabilities to investigate Alzheimers cases that run in families, those caused by a single gene.
The results of these studies all seemed to converge on one biological process: amyloid.
But these single-gene forms of Alzheimers are rareand account for maybe 2% to 3% of cases. Most cases of Alzheimers are caused by a complex interplay of many genes and the environment.
The field made the assumption that amyloid is the primary culprit in all forms of Alzheimers. It made perfect sense, because we see amyloid in all patients with Alzheimers, whether their disease is caused by a single gene or not. The amyloid finding was extremely exciting, and there was a sense that we were on the cusp of curing this devastating, horrible disease.
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Is There A Cure
“Currently, there is no cure for Alzheimer’s, though the FDA has approved two types of drugs, cholinesterase inhibitors and memantine, to treat symptoms. But these drugs can neither cure Alzheimer’s nor halt its progression. Also, they don’t work for every patient and eventually stop working for all patients,”says Jacob Donoghue, MD, PhD, co-founder of Beacon Biosignals, a neurotechnology company researching precision medicine for brain conditions like Alzheimer’s disease.
How Does Alzheimer’s Disease Affect The Brain
Scientists continue to unravel the complex brain changes involved in Alzheimers disease. Changes in the brain may begin a decade or more before symptoms appear. During this very early stage of Alzheimers, toxic changes are taking place in the brain, including abnormal buildups of proteins that form amyloid plaques and tau tangles. Previously healthy neurons stop functioning, lose connections with other neurons, and die. Many other complex brain changes are thought to play a role in Alzheimers as well.
The damage initially appears to take place in the hippocampus and the entorhinal cortex, which are parts of the brain that are essential in forming memories. As more neurons die, additional parts of the brain are affected and begin to shrink. By the final stage of Alzheimers, damage is widespread and brain tissue has shrunk significantly.
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The Cells’ Waste Management Is Destroyed By Alzheimer’s Disease
One of the causes of Alzheimers disease is the degeneration and loss of nerve cells in the brain as we age. A cell is like a finely tuned machinery. The cell needs energy to perform its tasks. The energy comes from energy factories called mitochondria.
In young, healthy cells, old or damaged mitochondria are removed from the cell in a process called mitophagy. The research group found that when we get older, we have more broken mitochondria, and the cells will not be able to remove all of them anymore. An accumulation of broken mitochondria clogs the cells ordinary processes and eventually, the cell will die.
Cells need the energy generated by the mitochondria to clear this “garbage”. Just like a machine will stop working if it is not maintained, says associate professor Evandro F. Fang, the leader of the research group.
Fang leads an international research group at The Institute of clinical medicine, University of Oslo and Akershus University Hospital.
Stopping And Concentrating On Plaques And Tangles
As with all illnesses, figuring out precisely what causes Alzheimers is vital to figuring out methods to forestall and deal with the situation.
Previous analysis has indicated that Alzheimers happens when two irregular mind buildings plaques and tangles harm and kill nerve cells, inflicting the reminiscence, considering and behavioral issues related to the illness.
Previous analysis has indicated that Alzheimers happens when two irregular mind buildings plaques and tangles harm and kill nerve cells.
Plaques are fragments of a protein referred to as beta-amyloid, which construct up in areas between nerve cells. Tangles are twisted fibers of a protein referred to as tau, which accumulate inside mind cells.
Though the jury remains to be out on the precise roles plaques and tangles play within the improvement of Alzheimers, research have advised that construct up of those proteins begins lengthy earlier than signs develop.
Proof means that the method of Alzheimers illness begins greater than a decade earlier than scientific signs seem, suggesting we might must intervene earlier to have a serious influence on the course of the illness, notably when utilizing therapies designed to forestall the event of irregular protein buildings plaques and tangles which might be considerable within the brains of individuals with Alzheimers, says Snyder.
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How Is Alzheimers Disease Treated
Alzheimers is complex, and it is therefore unlikely that any one drug or other intervention will successfully treat it in all people living with the disease.
Scientists are exploring many avenues to delay or prevent the disease as well as to treat its symptoms. In ongoing clinical trials, scientists are developing and testing several possible interventions. Under study are drug therapies aimed at a variety of disease interventions, as well as nondrug approaches such as physical activity, diet, cognitive training, and combinations of these. Just as we have many treatments for heart disease and cancer, we will likely need many options for treating Alzheimers. Precision medicine getting the right treatment to the right person at the right time will likely play a major role.
Current approaches to treating Alzheimers focus on helping people maintain mental function, treating the underlying disease process, and managing behavioral symptoms.
Identifying Who’s At Risk Of Dementia
Experts know that damage to the brain caused by Alzheimer’s disease can start many years before symptoms appear. If people at risk of Alzheimer’s could be identified at an early stage, it is hoped that treatments could be offered that would slow down or even stop the disease.
A major study, called PREVENT, concentrates on people in their 40s and 50s to identify those who are at greater risk of developing Alzheimer’s . It aims to understand what is happening in their brains before symptoms appear.
Specialised brain scans, known as PET scans, have been developed to study two proteins in the brains of those with Alzheimer’s disease. The aim is to increase the understanding of the disease process, and also to identify those people who will benefit most from new drug treatments.
Although PET scans are sometimes used to help with a dementia diagnosis, these highly specialised scans are usually only available as part of clinical trials.
A number of different trials are now under way in people who are currently well but are at increased risk of Alzheimer’s disease.
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May Have Found A Cure For Alzheimer`s
Researchers at the University of Oslo could be close to a breakthrough in the treatment of Alzheimers Disease.
Alzheimers is currently the most common form of dementia. Between 77,000 and 104,000 people have dementia in Norway, and 60 to 70 percent of these are Alzheimer’s patients. 12 to 15 percent of people over 80 years old is affected by the disease to some degree.
In a study published in Nature Neuroscience, researchers at the University of Oslo and Akershus University Hospital are now launching a new direction of treatment regarding Alzheimer’s. They have found that the cells of Alzheimer’s patients are not able to get rid of enough waste materials. There seems to be an accumulation of waste materials in the brain which causes brain cells to die. However, by stimulating the cells’ own self-cleansing system, it is possible to stop the disease.
Why Don’t We Have A Cure Yet
Since the first recorded discovery of Alzheimer’s disease in 1906, there has been disappointingly slow progress in discovering drugs that prevent or even delay it. There are a few reasons why this could be:
1. By the time symptoms of dementia present themselves, a lot of damage has already been done to the brain. So far, drugs have been tested on and developed for patients whose dementia has progressed too far to give effective results.
2. Dementia affects the whole brain and involves lots of pathways, proteins and cells going wrong. This makes research a lot more complicated and reduces the likelihood of a single miracle cure, as there is no single ‘thing’ to target. That’s why our name features dementias in the plural because there are lots of different types, and lots of diseases that can cause it .
3. Historically, dementia has been poorly understood, partially due to a lack of funding for research and drug development. Typically, areas that yield lots of promising results, and fields with a long-term payoff, get approved for funding, like physical conditions and childhood diseases. Because dementia most commonly affects older people and is a notoriously difficult condition to treat, it hasn’t received as much funding in the past.
But all that’s changing thanks in part to DPUK and the wealth of information in our Data Portal.
Listen to our interview with DPUK’s director, Professor John Gallacher, on the future of dementia research:
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Hitting Alzheimers Disease In Early Stage
Founded in 2008, AgeneBio is a pharmaceutical company based out of Indianapolis that has raised a total of $11 million to date. The company is focused on developing treatments for mild cognitive impairment , a minor condition of memory loss that precedes dementia from Alzheimers and other neurodegenerative diseases. AgeneBio successfully ran a Phase II clinical trial in 2014 on 34 individuals with its lead therapeutic candidate, AGB101, for MCI. AGB101 was originally designed to treat epilepsy and has a well-characterized safety profile. The trial showed improved mental performance and memory after only a two-week course of the drug. Phase 3 trials are planned for 2018. A second drug candidate thats prepared to enter Phase I trials, GABAA, is also still in the works.
Why Is It So Hard To Find A Cure For Alzheimers
People are living longer now than ever before, but with this triumph comes a truly unfortunate foe Alzheimer’s disease. Symptoms of the progressive brain disorder, which is the most common cause of dementia for older adults, typically start to show up around age 65, just when many people retire and plan to start enjoying their golden years.
This incurable disease is listed as the sixth leading cause of death for older people in the U.S., but the NIH says more recent estimates indicate it should rank third, behind only cancer and heart disease. Worse, Alzheimer’s is the only disease in the top 10 causes of death in the U.S. for which there is no cure, no means of prevention and no treatment to slow down the disease.
David Lusk, founder of an issue advocacy consulting company Key Advocacy in Arlington, Virginia, knows all too well the tragedy of this disease, having watched his mother’s decline. She began exhibiting symptoms like short-term memory loss, struggling with basic paperwork and making decisions with difficulty at age 65, but was not diagnosed until age 70 in 2008.
“By early 2012, my mother no longer believed I was her son,” he emails. “It was crushing to have my own mother think she wasn’t my mother and she stopped saying ‘I love you.’ That is the most painful thing to ever endure never hearing your own mother saying she loves you ever again.”
So, what gives? Why is it so hard to find a treatment for Alzheimer’s?
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Tau Vaccines May Be The Future For Alzheimers Therapeutics But They Need More Time To Prove Themselves
Regardless of the studys results, Long believes that therapies that aim to lower pathologic tau in the brain make sense and that antibody-mediated clearance is a good strategy to do it. I am excited for the potential of tau-based therapies, he adds, while warning, I do not expect the pathway to be smooth and I am sure there will be some roadblocks to developing effective therapies along the way.
Like a juicy steak my dog has yet to ingest, finding effective therapies to treat or prevent Alzheimers disease is a dream we all want to come true as soon as possible. Vaccines may be able to get us there sooner than later.
LinkedIn image: Koldunov/Shutterstock