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How Close Is A Cure For Alzheimer’s

A Comprehensive Analysis Of Alzheimers Disease Drug Development

How close are we to finding a cure for dementia? Professor Nick Fox

Monday, July 31, 2017 – 2 a.m.

Every 66 seconds someone in the United States is diagnosed with Alzheimers disease and by 2030, its estimated that 75 million people worldwide will be affected. The implications of this devastating disease reach far beyond those afflicted, causing turmoil both socially and economically. This growing health crisis is referred to as the grey tsunami and carries an estimated cost of $1 trillion a financial burden no government can bear.

With the grey tsunami an eminent threat lurking on the horizon, the Obama Administration and several other member nations attending the 2013 G8 Dementia Summit established a goal of developing a meaningful treatment for AD by 2025. Since then, we have been in a race to develop a cure or treatment and the stakes couldnt be higher.

The clock is ticking. In an effort to better understand where we are at in the AD drug development process, I along with fellow colleagues at Cleveland Clinic Lou Ruvo Center for Brain Health as well as researchers from Touro University and Global Alzheimers Platform have begun a yearly analysis of the AD drug pipeline.

So what can be done to improve the drug testing process? The answer: a lot. Our paper serves as a call to action and notes several areas we believe can significantly advance drug development. As one of the leading research institutes, the Lou Ruvo Center for Brain Health is ready to help orchestrate the changes needed and the time do so is now.

Opiniona Promising Psychedelic Drug Is Facing A Sadly Predictable Stigma

How we depict Alzheimer’s patients needs to change, too. So many families hide diagnoses, even after a loved one dies. Positioning Alzheimer’s this way makes it seem shameful. Focusing on a person’s strengths, rather than deficits, can help reframe how people feel about the disease. We should be talking about “living with Alzheimer’s” and portraying vibrant people engaging in regular activities, which will help increase understanding of the disease journey and decrease stigma.

June’s summer solstice the day with the most light has become associated with Alzheimer’s, encouraging the world to fight the darkness of the disease. If we have any hope of preventing or curing this devastating illness, we need to bring patients out of the darkness and into a world of greater acceptance and understanding.

Brenda K. Foster, M.P.A., is senior vice president of Vanguard Communications in Washington, D.C., and an instructor for the graduate program at American Universitys School of Communications. She was named a 2019 PR News Top Woman in PR for her impact on the field of strategic communications and public relations.

Fdas Accelerated Approval Program

Aducanumab was approved through the FDAs Accelerated Approval Program, which provides a path for earlier approval of drugs that treat certain serious conditions. This helps people living with the disease gain earlier access to the treatment. The approval of aducanumab was based on the ability of the drug to reduce amyloid in the brain. When using the accelerated approval pathway, drug companies are required to conduct additional studies to determine whether there is in fact clinical benefit after the drug is approved. If the follow-up trial fails to verify clinical benefit, the FDA may withdraw approval of the drug. Results of the phase 4 clinical trial for aducanumab are expected to be available by early 2030.

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Treatment For Moderate To Severe Alzheimers

A medication known as memantine, an N-methyl D-aspartate antagonist, is prescribed to treat moderate to severe Alzheimers disease. This drugs main effect is to decrease symptoms, which could enable some people to maintain certain daily functions a little longer than they would without the medication. For example, memantine may help a person in the later stages of the disease maintain his or her ability to use the bathroom independently for several more months, a benefit for both the person with Alzheimer’s and caregivers.

Memantine is believed to work by regulating glutamate, an important brain chemical. When produced in excessive amounts, glutamate may lead to brain cell death. Because NMDA antagonists work differently from cholinesterase inhibitors, the two types of drugs can be prescribed in combination.

The FDA has also approved donepezil, the rivastigmine patch, and a combination medication of memantine and donepezil for the treatment of moderate to severe Alzheimers.

Drug Name For More Information
  • Intravenous: Dose is determined by a persons weight given over one hour every four weeks most people will start with a lower dose and over a period of time increase the amount of medicine to reach the full prescription dose
  • Tablet: Once a day dosage may be increased over time if well tolerated
  • Orally disintegrating tablet: Same dosing regimen as above

The Search For A Cure

Advances in Dementia Treatment: Current and Future ...

Scientists at Cornell University found a link between stalled blood vessels in the brain and the symptoms of Alzheimers. These stalled vessels limit blood flow to the brain by up to 30 percent. In experiments with laboratory mice, when the blood cells causing the stalls were removed, the mice performed better on memory tests.

The researchers are working to develop Alzheimer’s treatments that remove the stalls in mice in the hope they can apply these methods to humans. But analyzing the brain images to find the stalled capillaries is hard and time consuming. It could take a trained laboratory technician six to 12 months to analyze each weeks worth of data collection.

So, Cornell researchers created Stall Catchers to make finding the stalled blood vessels into a game that anyone can play. The game relies on the power of the crowd multiple confirmed answers before determining whether a vessel is stalled or flowing.

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Co-author Professor Mark Carr, of Leicester University, said: If these results were replicated in human trials, then it could be transformative.

It opens up the possibility to not only treat Alzheimers but also to potentially vaccinate against the disease before the symptoms appear.

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Citizen Science Builds Community

Since its inception is 2016, he project has grown steadily, addressing various datasets and uncovering new insights about Alzheimers disease. Citizen scientists who play the game identify blood vessels as flowing or stalled, earning points for their classifications.

One way Stall Catchers makes this research fun is by allowing volunteers to form teams and engage in friendly competition. Stall Catchers has always been about bridging communities. Our volunteer Catchers are transplants from other citizen science projects, Alzheimer’s caregivers, scientists, gamers, grandparents, grandchildren, students, library patrons and the list goes on, says Pietro Michelucci, director of the Human Computation Institute and Stall Catchers creator.

Stall Catchers is a SciStarter affiliate project, meaning that they have partnered with SciStarter to engage citizen scientists from around the world. That includes volunteers from corporate partners like Verizon, through their volunteer program. With SciStarter, Verizon volunteers are on-boarded to meaningfully participate in Stall Catchers among other citizen science projects, a fact that Michelucci appreciates.

One of the volunteers, Cheryl Mulligan, appreciated the opportunity to do meaningful work toward ending Alzheimers. One of her loved ones had recently passed away from dementia when she started playing the game. It’s a very helpless feeling to deal with, whether it’s someone in your family or yourself, says Mulligan.

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Are We Really On The Brink Of A Cure For Alzheimers

A new study has inspired headlines claiming a cure for Alzheimers disease could be available within six years but are we genuinely on the verge of an effective treatment?

Given the physical, emotional and financial cost that Alzheimers and similar dementias inflict something thats only going to get worse as the population ages this would obviously be a massive boon. But as always, the picture is a lot more complex.

In fairness to the researchers at Cambridge and Lund universities, the press release itself shies away from such definite claims, only going so far as to say that trials for a drug modelled on their results could begin within two years. The more grandiose claims seem to come from a lead author on the study making comparisons with similar trials progress.

So is this yet another bold prediction that will end in crushing disappointment, as seems to be happening a lot lately?

And yet, that didnt seem to happen: drugs that supposedly remove amyloid plaques dont appear to cause any subsequent improvement in cognitive functioning. Could the whole premise that amyloid plaques cause Alzheimers be flawed?

According to many, yes. In more recent years, focus has shifted to other candidates, one of which is the build-up of misshapen proteins inside the brain cells, not between them. Neurofibrillary tangles, for example, occur when proteins become misshapen inside the neurons and potentially undermine the delicate cellular support systems.

A Message From Our Director

Could a treatment for Alzheimer’s disease be in the near future?

One question I am asked at nearly every public presentation is, How close are we to a cure for Alzheimers? No one can give a definite date for a cure or a meaningful treatment of Alzheimers disease. However, the process for achieving such a globally important milestone is clear. Whether we are one step away or 100 steps away, the next step must be testing of promising new treatments in clinical trials. Clinical trials are the only mechanism through which the FDA will approve drugs that can become widely available and can stop the tsunami of Alzheimers that is rushing toward us.

Clinical trials involve treating individuals who have symptoms of Alzheimers or who are at high risk for developing Alzheimers. Participants are assigned to a treatment or placebo, and neither the patient nor the doctor knows who is on active treatment and who is on placebo. All agents that will eventually be considered by the FDA must be tested in trials that include placebos. While some individuals are concerned that a placebo assignment is wasting time, this approach is the only means of generating valid data, and clinical trials are the only means of accessing promising therapies that are not yet approved.

I encourage you to consider taking a step with us: Visit for a list of active trials and for more information on participating in clinical trials.

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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.

‘cure’ Could Take Many Forms

As varied as the research pipeline is, most experts agree on one thing: When it comes to finding a way to stop, slow or prevent dementia, it wont boil down to one drug treatment or even one drug target. Rather, it will be a combination approach, perhaps involving drugs that clear the amyloid plaques, knock out the tau tangles, target problem proteins and improve the synaptic health of the nerve cells in the brain.

Patients may also receive nonpharmacological prescriptions from their doctors. Some of the most recent research has shown that cardiovascular health and cerebral vascular health play a critical role in overall brain health throughout ones lifetime. Exercise, diet and sleep have all been shown to reduce risk of cognitive decline in adults. Whats more, a landmark study in 2018 showed that intensive blood pressure control significantly lowered the chances that participants developed mild cognitive impairment.

The mishmash of therapies likely wont cure dementia, but as Rafii explains, we have very few cures in medicine. He and others in the field, including the DDFs Grant, are optimistic, however, that the ongoing advancements will lead to treatments that can delay the disease and improve the lives of millions.

What Im seeing is great progress in the building blocks, the foundation of new future therapeutic approaches, Grant says.

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Curing Alzheimers With Light Therapy

Founded in 2016, early stage startup Cognito Therapeutics was also spun out from MIT. The technology relies on treating patients with a device that exposes them to hour-long ultrafast oscillating light pulses to break down amyloid beta plaques in the brain. Think LED party strobe lights set to max. After a Series A round of funding from Chinese-based Morningside Venture Capital for an undisclosed amount and support through medical device incubator TheraNova, the strobing LED technology behind Cognito Therapeutics just began Phase I/II clinical trials in April 2018 with 60 patients using a wristband Flicker device over a six-month period. Sorry, looks like were not about to see Alzheimers-curing rave parties any time soon.

Why Is It So Hard To Find A Cure For Alzheimers

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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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Alzheimers Vaccine And Immunotherapy

Researchers have been attempting to develop a vaccine for Alzheimers disease for almost a decade. The strategy behind the immunotherapy approach is to use the bodys own immune system to destroy beta-amyloid plaques.

The first Alzheimers vaccine was tested in clinical trials in 2001. However, the trial was prematurely halted because six percent of participants developed serious brain inflammation. However, the vaccination did appear to benefit thinking and memory in some unaffected participants who were monitored after the end of the trial. Researchers have now developed a safer vaccine by using antibodies against a smaller fragment of the beta-amyloid protein, which they hope will avoid the complications of the previous trial.

Another approach to developing a vaccine involves using immunoglobulin, a filtered human blood product containing antibodies. Immunoglobulin was shown to be successful in a very small trial of 8 people with mild Alzheimers disease, with most showing improvement on tests of cognitive function after treatment. Although this trial is very small, it suggests the potential for larger trials of immunoglobulin therapy, which may have safety advantages over other vaccination techniques. Although this initial research is promising, much more research needs to be done before we know whether this approach will work.

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To their surprise, the protein folded back on itself.

In tests, both the antibody and the engineered vaccine repaired the brains neuron function and increased glucose metabolism in the brain, bringing back the memories of the mice.

Co-author Professor Mark Carr, of Leicester University, said: If these results were replicated in human trials, then it could be transformative.

It opens up the possibility to not only treat Alzheimers but also to potentially vaccinate against the disease before the symptoms appear.

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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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