Unprecedented Recovery Documented in 10 Early-stage Alzheimer’s Patients
A new method has been shown effective in halting, even reversing Alzheimer’s in 10 early-stage patients.
The human toll is evident. Patients knowing they are going to progressively lose their minds, functionality, and their very lives, must somehow learn to live with the horrifying diagnosis of Alzheimer’s. Meanwhile their families shoulder the burden of care, and the anguish of knowing that someday they will no longer be recognized.
Around 5.4 million Americans currently live with this neurodegenerative disorder. This is the sixth most common cause of death in the U.S. By 2050, 13.8 million are projected to have it. Due to the enormous baby boomer generation aging, scientists are in a race to find better detection and treatment options. If not, the disease is predicted to bankrupt Medicare at some point within the next three decades. So the need for effective management is great. There is no way to predict who will get it, though there is a genetic propensity. It’s progressive, and there is no cure.
Alzheimer’s is caused by the buildup of amyloid beta plaques. With a tar-like consistency, these globules gunk up the brain, choking out neurons and tearing the connections between them apart. These plaques are aided by threats of another protein called tau, which block nutrients from reaching brain cells, starving them. Though today, a diagnosis of this disorder heralds a grim fate, a new study published in the journal Aging has the Alzheimer’s community cautiously optimistic.
Alzheimer’s pathogenesis or development.
Neuroscientists at the Buck Institute on Research and Aging in Novato, California in collaboration with colleagues at UCLA, have successfully halted, and in some cases reversed, the memory loss of 10 early-stage patients. Investigators employed a complete disease management program, involving a combination of therapies and approaches. Dr. Dale Bredesen was a co-author on this study. He called the outcome, “unprecedented.” Landing on the proper management strategy has proven difficult. While lots of treatment options were effective in animal test subjects, few have been successful in human trials. But here, a combined therapy known as The MEND program, has shown remarkable results.
MEND stands for metabolic enhancement for neurodegeneration. This involves a “36-point system” including a certain diet, lots of exercise, medications, vitamins, sleep optimization, and even electrical brain stimulation. Attacking the disease synergistically enhances the drug’s performance, according to Dr. Bredesen. He put it this way, "Imagine having a roof with 36 holes in it, and your drug patched one hole very well - the drug may have worked, a single 'hole' may have been fixed, but you still have 35 other leaks, and so the underlying process may not be affected much."
Instead, with the MEND system, researchers target many holes at once. Each patient in the study suffered from subjective cognitive impairment (SCI), mild cognitive impairment (MCI), and memory loss. In addition, nine of the patients carried a specific gene for Alzheimer’s, ApoE4. Five of the patients carried two copies of the gene. Their likelihood for developing the condition was 10 to 12 times greater.
Each patient took part in the MEND system. Researchers monitored their cases carefully over the course of two years. In the end, all 10 showed significant improvements in memory, and many patients were moved from the “abnormal” category into “normal” cognitive functioning. One 69-year-old man who was about to shut down his business, was instead able to retake the reigns, and even expand, since he showed so much improvement. Before, he had been unable to remember his work schedule, or recall the faces of those he interacted with. At the onset, his long-term memory recall was a scant three percent. He underwent treatment for 22 months. Afterward, he was tested again. His recall was now 84%.
Another patient, a 49-year-old woman who had trouble with facial recognition and verbal memory, found that after a few months on MEND, she was able to regain her ability to not only recall words, but to speak a foreign language. In yet another case, a 66-year-old who experienced MCI showed a 12% increase in hippocampus volume, discovered via MRI at the end of the study. The hippocampus is the region of the brain responsible for learning and memory, and where Alzheimer’s originates.
Researchers say these findings illustrate just how effective the MEND system is in reversing early cognitive decline, even in those who carry genetic markers for the disease. More personalized programs may even enhance the efficacy of Alzheimer’s drugs further, according to Dr. Bredesen. Though heartening, more studies, including those with a larger pool of participants, are needed to confirm these results and learn more about why it is so effective.
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A new method promises to capture an elusive dark world particle.
- Scientists working on the Large Hadron Collider (LHC) devised a method for trapping dark matter particles.
- Dark matter is estimated to take up 26.8% of all matter in the Universe.
- The researchers will be able to try their approach in 2021, when the LHC goes back online.
Researchers hope the technology will further our understanding of the brain, but lawmakers may not be ready for the ethical challenges.
- Researchers at the Yale School of Medicine successfully restored some functions to pig brains that had been dead for hours.
- They hope the technology will advance our understanding of the brain, potentially developing new treatments for debilitating diseases and disorders.
- The research raises many ethical questions and puts to the test our current understanding of death.
The image of an undead brain coming back to live again is the stuff of science fiction. Not just any science fiction, specifically B-grade sci fi. What instantly springs to mind is the black-and-white horrors of films like Fiend Without a Face. Bad acting. Plastic monstrosities. Visible strings. And a spinal cord that, for some reason, is also a tentacle?
But like any good science fiction, it's only a matter of time before some manner of it seeps into our reality. This week's Nature published the findings of researchers who managed to restore function to pigs' brains that were clinically dead. At least, what we once thought of as dead.
What's dead may never die, it seems
The researchers did not hail from House Greyjoy — "What is dead may never die" — but came largely from the Yale School of Medicine. They connected 32 pig brains to a system called BrainEx. BrainEx is an artificial perfusion system — that is, a system that takes over the functions normally regulated by the organ. The pigs had been killed four hours earlier at a U.S. Department of Agriculture slaughterhouse; their brains completely removed from the skulls.
BrainEx pumped an experiment solution into the brain that essentially mimic blood flow. It brought oxygen and nutrients to the tissues, giving brain cells the resources to begin many normal functions. The cells began consuming and metabolizing sugars. The brains' immune systems kicked in. Neuron samples could carry an electrical signal. Some brain cells even responded to drugs.
The researchers have managed to keep some brains alive for up to 36 hours, and currently do not know if BrainEx can have sustained the brains longer. "It is conceivable we are just preventing the inevitable, and the brain won't be able to recover," said Nenad Sestan, Yale neuroscientist and the lead researcher.
As a control, other brains received either a fake solution or no solution at all. None revived brain activity and deteriorated as normal.
The researchers hope the technology can enhance our ability to study the brain and its cellular functions. One of the main avenues of such studies would be brain disorders and diseases. This could point the way to developing new of treatments for the likes of brain injuries, Alzheimer's, Huntington's, and neurodegenerative conditions.
"This is an extraordinary and very promising breakthrough for neuroscience. It immediately offers a much better model for studying the human brain, which is extraordinarily important, given the vast amount of human suffering from diseases of the mind [and] brain," Nita Farahany, the bioethicists at the Duke University School of Law who wrote the study's commentary, told National Geographic.
An ethical gray matter
Before anyone gets an Island of Dr. Moreau vibe, it's worth noting that the brains did not approach neural activity anywhere near consciousness.
The BrainEx solution contained chemicals that prevented neurons from firing. To be extra cautious, the researchers also monitored the brains for any such activity and were prepared to administer an anesthetic should they have seen signs of consciousness.
Even so, the research signals a massive debate to come regarding medical ethics and our definition of death.
Most countries define death, clinically speaking, as the irreversible loss of brain or circulatory function. This definition was already at odds with some folk- and value-centric understandings, but where do we go if it becomes possible to reverse clinical death with artificial perfusion?
"This is wild," Jonathan Moreno, a bioethicist at the University of Pennsylvania, told the New York Times. "If ever there was an issue that merited big public deliberation on the ethics of science and medicine, this is one."
One possible consequence involves organ donations. Some European countries require emergency responders to use a process that preserves organs when they cannot resuscitate a person. They continue to pump blood throughout the body, but use a "thoracic aortic occlusion balloon" to prevent that blood from reaching the brain.
The system is already controversial because it raises concerns about what caused the patient's death. But what happens when brain death becomes readily reversible? Stuart Younger, a bioethicist at Case Western Reserve University, told Nature that if BrainEx were to become widely available, it could shrink the pool of eligible donors.
"There's a potential conflict here between the interests of potential donors — who might not even be donors — and people who are waiting for organs," he said.
It will be a while before such experiments go anywhere near human subjects. A more immediate ethical question relates to how such experiments harm animal subjects.
Ethical review boards evaluate research protocols and can reject any that causes undue pain, suffering, or distress. Since dead animals feel no pain, suffer no trauma, they are typically approved as subjects. But how do such boards make a judgement regarding the suffering of a "cellularly active" brain? The distress of a partially alive brain?
The dilemma is unprecedented.
Setting new boundaries
Another science fiction story that comes to mind when discussing this story is, of course, Frankenstein. As Farahany told National Geographic: "It is definitely has [sic] a good science-fiction element to it, and it is restoring cellular function where we previously thought impossible. But to have Frankenstein, you need some degree of consciousness, some 'there' there. [The researchers] did not recover any form of consciousness in this study, and it is still unclear if we ever could. But we are one step closer to that possibility."
She's right. The researchers undertook their research for the betterment of humanity, and we may one day reap some unimaginable medical benefits from it. The ethical questions, however, remain as unsettling as the stories they remind us of.
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