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Once upon a time, a powerful Sumerian king named Gilgamesh went on a quest, as such characters often do in these stories of myth and legend. Gilgamesh had witnessed the death of his best friend, Enkidu, and, fearing a similar fate, went in search of immortality. The great king failed to find the secret of eternal life but took solace that his deeds would live well beyond his mortal years.
Fast-forward four thousand years, give or take a century, and Gilgamesh (as famous as any B-list celebrity today, despite the passage of time) would probably be heartened to learn that many others have taken up his search for longevity. Today, though, instead of battling epic monsters and the machinations of fickle gods, those seeking to enhance and extend life are cutting-edge scientists and visionary entrepreneurs who are helping unlock the secrets of human biology.
Chief among them is Aubrey de Grey, a biomedical gerontologist who founded the SENS Research Foundation, a Silicon Valley-based research organization that seeks to advance the application of regenerative medicine to age-related diseases. SENS stands for Strategies for Engineered Negligible Senescence, a term coined by de Grey to describe a broad array (seven, to be precise) of medical interventions that attempt to repair or prevent different types of molecular and cellular damage that eventually lead to age-related diseases like cancer and Alzheimer’s.
Many of the strategies focus on senescent cells, which accumulate in tissues and organs as people age. Not quite dead, senescent cells stop dividing but are still metabolically active, spewing out all sorts of proteins and other molecules that can cause inflammation and other problems. In a young body, that’s usually not a problem (and probably part of general biological maintenance), as a healthy immune system can go to work to put out most fires.
However, as we age, senescent cells continue to accumulate, and at some point the immune system retires from fire watch. Welcome to old age.
Of Mice and Men
Researchers like de Grey believe that treating the cellular underpinnings of aging could not only prevent disease but significantly extend human lifespans. How long? Well, if you’re talking to de Grey, Biblical proportions—on the order of centuries.
De Grey says that science has made great strides toward that end in the last 15 years, such as the ability to copy mitochondrial DNA to the nucleus. Mitochondria serve as the power plant of the cell but are highly susceptible to mutations that lead to cellular degeneration. Copying the mitochondrial DNA into the nucleus would help protect it from damage.
Another achievement occurred about six years ago when scientists first figured out how to kill senescent cells. That discovery led to a spate of new experiments in mice indicating that removing these ticking-time-bomb cells prevented disease and even extended their lifespans. Now the anti-aging therapy is about to be tested in humans.
“As for the next few years, I think the stream of advances is likely to become a flood—once the first steps are made, things get progressively easier and faster,” de Grey tells Singularity Hub. “I think there’s a good chance that we will achieve really dramatic rejuvenation of mice within only six to eight years: maybe taking middle-aged mice and doubling their remaining lifespan, which is an order of magnitude more than can be done today.”
Not Horsing Around
Richard G.A. Faragher, a professor of biogerontology at the University of Brighton in the United Kingdom, recently made discoveries in the lab regarding the rejuvenation of senescent cells with chemical compounds found in foods like chocolate and red wine. He hopes to apply his findings to an animal model in the future—in this case,horses.
“We have been very fortunate in receiving some funding from an animal welfare charity to look at potential treatments for older horses,” he explains to Singularity Hub in an email. “I think this is a great idea. Many aspects of the physiology we are studying are common between horses and humans.”
What Faragher and his colleagues demonstrated in a paper published in BMC Cell Biology last year was that resveralogues, chemicals based on resveratrol, were able to reactivate a protein called a splicing factor that is involved in gene regulation. Within hours, the chemicals caused the cells to rejuvenate and start dividing like younger cells.
“If treatments work in our old pony systems, then I am sure they could be translated into clinical trials in humans,” Faragher says. “How long is purely a matter of money. Given suitable funding, I would hope to see a trial within five years.”
Show Them the Money
Faragher argues that the recent breakthroughs aren’t because a result of emerging technologies like artificial intelligence or the gene-editing tool CRISPR, but a paradigm shift in how scientists understand the underpinnings of cellular aging. Solving the “aging problem” isn’t a question of technology but of money, he says.
“Frankly, when AI and CRISPR have removed cystic fibrosis, Duchenne muscular dystrophy or Gaucher syndrome, I’ll be much more willing to hear tales of amazing progress. Go fix a single, highly penetrant genetic disease in the population using this flashy stuff and then we’ll talk,” he says. “My faith resides in the most potent technological development of all: money.”
De Grey is less flippant about the role that technology will play in the quest to defeat aging. AI, CRISPR, protein engineering, advances in stem cell therapies, and immune system engineering—all will have a part.
“There is not really anything distinctive about the ways in which these technologies will contribute,” he says. “What’s distinctive is that we will need all of these technologies, because there are so many different types of damage to repair and they each require different tricks.”
It’s in the Blood
A startup in the San Francisco Bay Area believes machines can play a big role in discovering the right combination of factors that lead to longer and healthier lives—and then develop drugs that exploit those findings.
BioAge Labs raised nearly $11 million last year for its machine learning platform that crunches big data sets to find blood factors, such as proteins or metabolites, that are tied to a person’s underlying biological age. The startup claims that these factors can predict how long a person will live.
“Our interest in this comes out of research into parabiosis, where joining the circulatory systems of old and young mice—so that they share the same blood—has been demonstrated to make old mice healthier and more robust,” Dr. Eric Morgen, chief medical officer at BioAge, tells Singularity Hub.
Based on that idea, he explains, it should be possible to alter those good or bad factors to produce a rejuvenating effect.
“Our main focus at BioAge is to identify these types of factors in our human cohort data, characterize the important molecular pathways they are involved in, and then drug those pathways,” he says. “This is a really hard problem, and we use machine learning to mine these complex datasets to determine which individual factors and molecular pathways best reflect biological age.”
Saving for the Future
Of course, there’s no telling when any of these anti-aging therapies will come to market. That’s why Forever Labs, a biotechnology startup out of Ann Arbor, Michigan, wants your stem cells now. The company offers a service to cryogenically freeze stem cells taken from bone marrow.
The theory behind the procedure, according to Forever Labs CEO Steven Clausnitzer, is based on research showing that stem cells may be a key component for repairing cellular damage. That’s because stem cells can develop into many different cell types and can divide endlessly to replenish other cells. Clausnitzer notes that there are upwards of a thousand clinical studies looking at using stem cells to treat age-related conditions such as cardiovascular disease.
However, stem cells come with their own expiration date, which usually coincides with the age that most people start experiencing serious health problems. Stem cells harvested from bone marrow at a younger age can potentially provide a therapeutic resource in the future.
“We believe strongly that by having access to your own best possible selves, you’re going to be well positioned to lead healthier, longer lives,” he tells Singularity Hub.
“There’s a compelling argument to be made that if you started to maintain the bone marrow population, the amount of nuclear cells in your bone marrow, and to re-up them so that they aren’t declining with age, it stands to reason that you could absolutely mitigate things like cardiovascular disease and stroke and Alzheimer’s,” he adds.
Clausnitzer notes that the stored stem cells can be used today in developing therapies to treat chronic conditions such as osteoarthritis. However, the more exciting prospect—and the reason he put his own 38-year-old stem cells on ice—is that he believes future stem cell therapies can help stave off the ravages of age-related disease.
“I can start reintroducing them not to treat age-related disease but to treat the decline in the stem-cell niche itself, so that I don’t ever get an age-related disease,” he says. “I don’t think that it equates to immortality, but it certainly is a step in that direction.”
Indecisive on Immortality
The societal implications of a longer-living human species are a guessing game at this point. We do know that by mid-century, the global population of those aged 65 and older will reach 1.6 billion, while those older than 80 will hit nearly 450 million, according to the National Academies of Science. If many of those people could enjoy healthy lives in their twilight years, an enormous medical cost could be avoided.
Faragher is certainly working toward a future where human health is ubiquitous. Human immortality is another question entirely.
“The longer lifespans become, the more heavily we may need to control birth rates and thus we may have fewer new minds. This could have a heavy ‘opportunity cost’ in terms of progress,” he says.
And does anyone truly want to live forever?
“There have been happy moments in my life but I have also suffered some traumatic disappointments. No [drug] will wash those experiences out of me,” Faragher says. “I no longer view my future with unqualified enthusiasm, and I do not think I am the only middle-aged man to feel that way. I don’t think it is an accident that so many ‘immortalists’ are young.
“They should be careful what they wish for.”
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Pedro Domingos on the Arms Race in Artificial Intelligence
Christoph Scheuermann and Bernhard Zand | Spiegel Online
“AI lowers the cost of knowledge by orders of magnitude. One good, effective machine learning system can do the work of a million people, whether it’s for commercial purposes or for cyberespionage. Imagine a country that produces a thousand times more knowledge than another. This is the challenge we are facing.”
Gene Therapy Could Free Some People From a Lifetime of Blood Transfusions
Emily Mullin | MIT Technology Review
“A one-time, experimental treatment for an inherited blood disorder has shown dramatic results in a small study. …[Lead author Alexis Thompson] says the effect on patients has been remarkable. ‘They have been tied to this ongoing medical therapy that is burdensome and expensive for their whole lives,’ she says. ‘Gene therapy has allowed people to have aspirations and really pursue them.’ ”
The Revolutionary Giant Ocean Cleanup Machine Is About to Set Sail
Adele Peters | Fast Company
“By the end of 2018, the nonprofit says it will bring back its first harvest of ocean plastic from the North Pacific Gyre, along with concrete proof that the design works. The organization expects to bring 5,000 kilograms of plastic ashore per month with its first system. With a full fleet of systems deployed, it believes that it can collect half of the plastic trash in the Great Pacific Garbage Patch—around 40,000 metric tons—within five years.”
Autonomous Boats Will Be on the Market Sooner Than Self-Driving Cars
Tracey Lindeman | Motherboard
“Some unmanned watercraft…may be at sea commercially before 2020. That’s partly because automating all ships could generate a ridiculous amount of revenue. According to the United Nations, 90 percent of the world’s trade is carried by sea and 10.3 billion tons of products were shipped in 2016.”
Style Is an Algorithm
Kyle Chayka | Racked
“Confronting the Echo Look’s opaque statements on my fashion sense, I realize that all of these algorithmic experiences are matters of taste: the question of what we like and why we like it, and what it means that taste is increasingly dictated by black-box robots like the camera on my shelf.”
How Apple Will Use AR to Reinvent the Human-Computer Interface
Tim Bajarin | Fast Company
“It’s in Apple’s DNA to continually deliver the ‘next’ major advancement to the personal computing experience. Its innovation in man-machine interfaces started with the Mac and then extended to the iPod, the iPhone, the iPad, and most recently, the Apple Watch. Now, get ready for the next chapter, as Apple tackles augmented reality, in a way that could fundamentally transform the human-computer interface.”
Advanced Microscope Shows Cells at Work in Incredible Detail
Steve Dent | Engadget
“For the first time, scientists have peered into living cells and created videos showing how they function with unprecedented 3D detail. Using a special microscope and new lighting techniques, a team from Harvard and the Howard Hughes Medical Institute captured zebrafish immune cell interactions with unheard-of 3D detail and resolution.”
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It is one of the top 10 deadliest diseases in the United States, and it cannot be cured or prevented. But new studies are finding ways to diagnose Alzheimer’s disease in its earliest stages, while some of the latest research says technologies like artificial intelligence can detect dementia years before the first symptoms occur.
These advances, in turn, will help bolster clinical trials seeking a cure or therapies to slow or prevent the disease. Catching Alzheimer’s disease or other forms of dementia early in their progression can help ease symptoms in some cases.
“Often neurodegeneration is diagnosed late when massive brain damage has already occurred,” says professor Francis L Martin at the University of Central Lancashire in the UK, in an email to Singularity Hub. “As we know more about the molecular basis of the disease, there is the possibility of clinical interventions that might slow or halt the progress of the disease, i.e., before brain damage. Extending cognitive ability for even a number of years would have huge benefit.”
Martin is the principal investigator on a project that has developed a technique to analyze blood samples to diagnose Alzheimer’s disease and distinguish between other forms of dementia.
The researchers used sensor-based technology with a diamond core to analyze about 550 blood samples. They identified specific chemical bonds within the blood after passing light through the diamond core and recording its interaction with the sample. The results were then compared against blood samples from cases of Alzheimer’s disease and other neurodegenerative diseases, along with those from healthy individuals.
“From a small drop of blood, we derive a fingerprint spectrum. That fingerprint spectrum contains numerical data, which can be inputted into a computational algorithm we have developed,” Martin explains. “This algorithm is validated for prediction of unknown samples. From this we determine sensitivity and specificity. Although not perfect, my clinical colleagues reliably tell me our results are far better than anything else they have seen.”
Martin says the breakthrough is the result of more than 10 years developing sensor-based technologies for routine screening, monitoring, or diagnosing neurodegenerative diseases and cancers.
“My vision was to develop something low-cost that could be readily applied in a typical clinical setting to handle thousands of samples potentially per day or per week,” he says, adding that the technology also has applications in environmental science and food security.
The new test can also distinguish accurately between Alzheimer’s disease and other forms of neurodegeneration, such as Lewy body dementia, which is one of the most common causes of dementia after Alzheimer’s.
“To this point, other than at post-mortem, there has been no single approach towards classifying these pathologies,” Martin notes. “MRI scanning is often used but is labor-intensive, costly, difficult to apply to dementia patients, and not a routine point-of-care test.”
Canadian researchers at McGill University believe they can predict Alzheimer’s disease up to two years before its onset using big data and artificial intelligence. They developed an algorithm capable of recognizing the signatures of dementia using a single amyloid PET scan of the brain of patients at risk of developing the disease.
Alzheimer’s is caused by the accumulation of two proteins—amyloid beta and tau. The latest research suggests that amyloid beta leads to the buildup of tau, which is responsible for damaging nerve cells and connections between cells called synapses.
The work was recently published in the journal Neurobiology of Aging.
“Despite the availability of biomarkers capable of identifying the proteins causative of Alzheimer’s disease in living individuals, the current technologies cannot predict whether carriers of AD pathology in the brain will progress to dementia,” Sulantha Mathotaarachchi, lead author on the paper and an expert in artificial neural networks, tells Singularity Hub by email.
The algorithm, trained on a population with amnestic mild cognitive impairment observed over 24 months, proved accurate 84.5 percent of the time. Mathotaarachchi says the algorithm can be trained on different populations for different observational periods, meaning the system can grow more comprehensive with more data.
“The more biomarkers we incorporate, the more accurate the prediction could be,” Mathotaarachchi adds. “However, right now, acquiring [the] required amount of training data is the biggest challenge. … In Alzheimer’s disease, it is known that the amyloid protein deposition occurs decades before symptoms onset.”
Unfortunately, the same process occurs in normal aging as well. “The challenge is to identify the abnormal patterns of deposition that lead to the disease later on,” he says
One of the key goals of the project is to improve the research in Alzheimer’s disease by ensuring those patients with the highest probability to develop dementia are enrolled in clinical trials. That will increase the efficiency of clinical programs, according to Mathotaarachchi.
“One of the most important outcomes from our study was the pilot, online, real-time prediction tool,” he says. “This can be used as a framework for patient screening before recruiting for clinical trials. … If a disease-modifying therapy becomes available for patients, a predictive tool might have clinical applications as well, by providing to the physician information regarding clinical progression.”
Pixel by Pixel Prediction
Private industry is also working toward improving science’s predictive powers when it comes to detecting dementia early. One startup called Darmiyan out of San Francisco claims its proprietary software can pick up signals before the onset of Alzheimer’s disease by up to 15 years.
Darmiyan didn’t respond to a request for comment for this article. Venture Beat reported that the company’s MRI-analyzing software “detects cell abnormalities at a microscopic level to reveal what a standard MRI scan cannot” and that the “software measures and highlights subtle microscopic changes in the brain tissue represented in every pixel of the MRI image long before any symptoms arise.”
Darmiyan claims to have a 90 percent accuracy rate and says its software has been vetted by top academic institutions like New York University, Rockefeller University, and Stanford, according to Venture Beat. The startup is awaiting FDA approval to proceed further but is reportedly working with pharmaceutical companies like Amgen, Johnson & Johnson, and Pfizer on pilot programs.
“Our technology enables smarter drug selection in preclinical animal studies, better patient selection for clinical trials, and much better drug-effect monitoring,” Darmiyan cofounder and CEO Padideh Kamali-Zare told Venture Beat.
An estimated 5.5 million Americans have Alzheimer’s, and one in 10 people over age 65 have been diagnosed with the disease. By mid-century, the number of Alzheimer’s patients could rise to 16 million. Health care costs in 2017 alone are estimated to be $259 billion, and by 2050 the annual price tag could be more than $1 trillion.
In sum, it’s a disease that cripples people and the economy.
Researchers are always after more data as they look to improve outcomes, with the hope of one day developing a cure or preventing the onset of neurodegeneration altogether. If interested in seeing this medical research progress, you can help by signing up on the Brain Health Registry to improve the quality of clinical trials.
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