The virus that could cure parkinson’s, alzheimer’s, and more — nova next _ pbs

In 2004, the British chemist Chris Dobson speculated that there might be a universal elixir out there that could combat not just alpha-synuclein for Parkinson’s but the amyloids caused by many protein-misfolding diseases at once. What are the symptoms of alzheimer’s disease Remarkably, in that same year an Israeli scientist named Beka Solomon discovered an unlikely candidate for this elixir, a naturally occurring microorganism called a phage.

Solomon, a professor at Tel Aviv University, made a serendipitous discovery one day when she was testing a new class of agents against Alzheimer’s disease. Sign of alzheimer’s disease If it pans out, it might mark the beginning of the end of Alzheimer’s, Parkinson’s, and many other neurodegenerative diseases.

Protein involved in alzheimer’s disease It’s a remarkable story, and the main character isn’t Solomon or any other scientist but a humble virus that scientists refer to as M13.

Among the many varieties of viruses, there is a kind that only infects bacteria. Alzheimer disease definition psychology Known as bacteriophages, or just phages, these microbes are ancient (over three billion years old) and ubiquitous: they’re found everywhere from the ocean floor to human stomachs. How do you get alzheimer’s disease The phage M13’s goal is to infect just one type of bacteria, Escherichia coli, or E. Alzheimer’s disease information coli, which can be found in copious amounts in the intestines of mammals. History of alzheimer’s disease Like other microorganisms, phages such as M13 have only one purpose: to pass on their genes. Stages of alzheimer disease pdf In order to do this, they have developed weapons to enable them to invade, take over, and even kill their bacterial hosts. Characteristics of alzheimer’s disease Before the advent of antibiotics, in fact, doctors occasionally used phages to fight otherwise incurable bacterial infections.

To understand Solomon’s interest in M13 requires a little background about her research. Prognosis of alzheimer’s disease Solomon is a leading Alzheimer’s researcher, renowned for pioneering so-called immunotherapy treatments for the disease. Alzheimer’s disease definition Immunotherapy employs specially made antibodies, rather than small molecule drugs, to target the disease’s plaques and tangles. Alzheimer’s disease is caused by As high school students learn in biology class, antibodies are Y-shaped proteins that are part of the body’s natural defense against infection. Diagnosis of alzheimer’s disease These proteins are designed to latch onto invaders and hold them so that they can be destroyed by the immune system. The stages of alzheimer’s disease But since the 1970s, molecular biologists have been able to genetically engineer human-made antibodies, fashioned to attack undesirable interlopers like cancer cells. Alzheimer’s disease diagnosis In the 1990s, Solomon set out to prove that such engineered antibodies could be effective in attacking amyloid-beta plaques in Alzheimer’s as well.

In 2004, she was running an experiment on a group of mice that had been genetically engineered to develop Alzheimer’s disease plaques in their brains. Alzheimer’s disease wiki She wanted to see if human-made antibodies delivered through the animals’ nasal passages would penetrate the blood-brain barrier and dissolve the amyloid-beta plaques in their brains. Alzheimer’s disease pictures Seeking a way to get more antibodies into the brain, she decided to attach them to M13 phages in the hope that the two acting in concert would better penetrate the blood-brain barrier, dissolve more of the plaques, and improve the symptoms in the mice—as measured by their ability to run mazes and perform similar tasks. How do you test for alzheimer disease At the time, Solomon had no clear idea how a simple phage could dissolve Alzheimer’s plaques.

Solomon divided the rodents into three groups. Early onset alzheimer’s disease She gave the antibody to one group. What causes alzheimer’s disease The second group got the phage-antibody combination, which she hoped would have an enhanced effect in dissolving the plaques. What are the major symptoms of alzheimer’s disease And as a scientific control, the third group received the plain phage M13.

Because M13 cannot infect any organism except E. Medical definition of alzheimer’s disease coli, she expected that the control group of mice would get absolutely no benefit from the phage. What is alzheimer’s disease But, surprisingly, the phage by itself proved highly effective at dissolving amyloid-beta plaques and in laboratory tests improved the cognition and sense of smell of the mice. Alzheimer’s disease symptoms She repeated the experiment again and again, and the same thing happened. What age can you get alzheimer’s disease “The mice showed very nice recovery of their cognitive function,” Solomon says. Cause of alzheimer’s disease And when Solomon and her team examined the brains of the mice, the plaques had been largely dissolved. What are the treatment of alzheimer disease She ran the experiment for a year and found that the phage-treated mice had 80% fewer plaques than untreated ones. Familial alzheimer’s disease Solomon had no clear idea how a simple phage could dissolve Alzheimer’s plaques, but given even a remote chance that she had stumbled across something important, she decided to patent M13’s therapeutic properties for the University of Tel Aviv. Alzheimer’s disease treatment options According to her son Jonathan, she even “joked about launching a new company around the phage called NeuroPhage. Alzheimer’s disease pdf But she wasn’t really serious about it.”

The following year, Jonathan Solomon—who’d just completed more than a decade in Israel’s special forces, during which time he got a BS in physics and an MS in electrical engineering—traveled to Boston to enroll at the Harvard Business School. About alzheimer’s disease While he studied for his MBA, Jonathan kept thinking about the phage his mother had investigated and its potential to treat terrible diseases like Alzheimer’s. Alzheimer disease test peanut butter At Harvard, he met many brilliant would-be entrepreneurs, including the Swiss-educated Hampus Hillerstrom, who, after studying at the University of St. Gallen near Zurich, had worked for a European biotech venture capital firm called HealthCap.

Following the first year of business school, both students won summer internships: Solomon at the medical device manufacturer Medtronic and Hillerstrom at the pharmaceutical giant AstraZeneca. Pathophysiology of alzheimer disease pdf But as Hillerstrom recalls, they returned to Harvard wanting more: “We had both spent…I would call them ‘weird summers’ in large companies, and we said to each other, ‘Well, we have to do something more dynamic and more interesting.’ ”

In their second year of the MBA, Solomon and Hillerstrom took a class together in which students were tasked with creating a new company on paper. How early can you get alzheimer’s disease The class, Solomon says, “was called a field study, and the idea was you explore a technology or a new business idea by yourself while being mentored by a Harvard Business School professor. Signs and symptoms of alzheimer’s disease So, I raised the idea with Hampus of starting a new company around the M13 phage as a class project. Alzheimer’s disease test At the end of that semester, we developed a mini business plan. Can you die from alzheimer’s disease And we got on so well that we decided that it was worth a shot to do this for real.”

In 2007, with $150,000 in seed money contributed by family members, a new venture, NeuroPhage Pharmaceuticals, was born. What are the causes and symptoms of alzheimer disease After negotiating a license with the University of Tel Aviv to explore M13’s therapeutic properties, Solomon and Hillerstrom reached out to investors willing to bet on M13’s potential therapeutic powers. Types of alzheimer’s disease By January 2008, they had raised over $7 million and started hiring staff.

Their first employee—NeuroPhage’s chief scientific officer—was Richard Fisher, a veteran of five biotech start-ups. Alzheimer’s disease meaning Fisher recalls feeling unconvinced when he first heard about the miraculous phage. Is there treatment for alzheimer’s disease “But the way it’s been in my life is that it’s really all about the people, and so first I met Jonathan and Hampus and I really liked them. Stages of dementia alzheimer’s disease And I thought that within a year or so we could probably figure out if it was an artifact or whether there was something really to it, but I was extremely skeptical.” “Why would a phage do this to amyloid fibers?”

Fisher set out to repeat Beka Solomon’s mouse experiments and found that with some difficulty he was able to show the M13 phage dissolved amyloid-beta plaques when the phage was delivered through the rodents’ nasal passages. Alzheimer’s disease history Over the next two years, Fisher and his colleagues then discovered something totally unexpected: that the humble M13 virus could also dissolve other amyloid aggregates—the tau tangles found in Alzheimer’s and also the amyloid plaques associated with other diseases, including alpha-synuclein (Parkinson’s), huntingtin (Huntington’s disease), and superoxide dismutase (amyotrophic lateral sclerosis). Facts about alzheimer’s disease The phage even worked against the amyloids in prion diseases (a class that includes Creutzfeldt-Jakob disease). Test for alzheimer’s disease Fisher and his colleagues demonstrated this first in test tubes and then in a series of animal experiments. What causes alzheimer disease yahoo Astonishingly, the simple M13 virus appeared in principle to possess the properties of a “pan therapy,” a universal elixir of the kind the chemist Chris Dobson had imagined.

This phage’s unique capacity to attack multiple targets attracted new investors in a second round of financing in 2010. Signs and symptoms of alzheimer disease pdf Solomon recalls feeling a mix of exuberance and doubt: “We had something interesting that attacks multiple targets, and that was exciting. Alzheimer disease caused by virus On the other hand, we had no idea how the phage worked.” The Key

That wasn’t their only problem. How can you die from alzheimer’s disease Their therapeutic product, a live virus, it turned out, was very difficult to manufacture. Causes of alzheimer’s disease It was also not clear how sufficient quantities of viral particles could be delivered to human beings. Signs of alzheimer’s disease The methods used in animal experiments—inhaled through the nose or injected directly into the brain—were unacceptable, so the best option available appeared to be a so-called intrathecal injection into the spinal canal. Alzheimer’s disease treatment guidelines As Hillerstrom says, “It was similar to an epidural; this was the route we had decided to deliver our virus with.”

While Solomon and Hillerstrom worried about finding an acceptable route of administration, Fisher spent long hours trying to figure out the phage’s underlying mechanism of action. Alzheimer disease drugs list “Why would a phage do this to amyloid fibers? And we really didn’t have a very good idea, except that under an electron microscope the phage looked a lot like an amyloid fiber; it had the same dimensions.”

Boston is a town with enormous scientific resources. Definition of alzheimer’s disease Less than a mile away from NeuroPhage’s offices was MIT, a world center of science and technology. Alzheimer’s disease prevalence In 2010, Fisher recruited Rajaraman Krishnan—an Indian postdoctoral student working in an MIT laboratory devoted to protein misfolding—to investigate the M13 puzzle. How do you die from alzheimer’s disease Krishnan says he was immediately intrigued. Family alzheimer’s disease The young scientist set about developing some new biochemical tools to investigate how the virus worked and also devoured the scientific literature about phages. How to treat alzheimer’s disease It turned out that scientists knew quite a lot about the lowly M13 phage. Symptoms of alzheimer’s disease Virologists had even created libraries of mutant forms of M13. Etiology of alzheimer’s disease By running a series of experiments to test which mutants bound to the amyloid and which ones didn’t, Krishnan was able to figure out that the phage’s special abilities involved a set of proteins displayed on the tip of the virus, called GP3. What are early signs of alzheimer’s disease “We tested the different variants for examples of phages with or without tip proteins, and we found that every time we messed around with the tip proteins, it lowered the phage’s ability to attach to amyloids,” Krishnan says.

Virologists, it turned out, had also visualized the phage’s structure using X-ray crystallography and nuclear magnetic resonance imaging. Mental effects of alzheimer disease Based on this analysis, those microbiologists had predicted that the phage’s normal mode of operation in nature was to deploy the tip proteins as molecular keys; the keys in effect enabled the parasite to “unlock” E. Alzheimer’s disease research paper coli bacteria and inject its DNA. Prognosis of alzheimer disease today Sometime in 2011, Krishnan became convinced that the phage was doing something similar when it bound to toxic amyloid aggregates. Disease alzheimer’s The secret of the phage’s extraordinary powers, he surmised, lay entirely in the GP3 protein.

As Fisher notes, this is serendipitous. Alzheimer’s disease stages Just by “sheer luck, M13’s keys not only unlock E. Alzheimer disease is caused by lack of which neurotransmitter coli; they also work on clumps of misfolded proteins.” The odds of this happening by chance, Fisher says, are very small. Definition alzheimer’s disease “Viruses have exquisite specificity in their molecular mechanisms, because they’re competing with each other…and you need to have everything right, and the two locks need to work exactly the way they are designed. Diagnosis and treatment of alzheimer’s disease And this one way of getting into bacteria also works for binding to the amyloid plaques that cause many chronic diseases of our day.”

Having proved the virus’s secret lay in a few proteins at the tip, Fisher, Krishnan, and their colleagues wondered if they could capture the phage’s amyloid-busting power in a more patient friendly medicine that did not have to be delivered by epidural. First sign of alzheimer’s disease So over the next two years, NeuroPhage’s scientists engineered a new antibody (a so-called fusion protein because it is made up of genetic material from different sources) that displayed the critical GP3 protein on its surface so that, like the phage, it could dissolve amyloid plaques. Alzheimer’s disease treatment Fisher hoped this novel manufactured product would stick to toxic aggregates just like the phage.

By 2013, NeuroPhage’s researchers had tested the new compound, which they called NPT088, in test tubes and in animals, including nonhuman primates. How to diagnose alzheimer’s disease It performed spectacularly, simultaneously targeting multiple misfolded proteins such as amyloid beta, tau, and alpha-synuclein at various stages of amyloid assembly. Alzheimer disease international wikipedia According to Fisher, NPT088 didn’t stick to normally folded individual proteins; it left normal alpha-synuclein alone. Define alzheimer’s disease It stuck only to misfolded proteins, not just dissolving them directly, but also blocking their prion-like transmission from cell to cell: “It targets small aggregates, those oligomers, which some scientists consider to be toxic. Alzheimer’s disease international And it targets amyloid fibers that form aggregates. Symptoms alzheimer’s disease But it doesn’t stick to normally folded individual proteins.” And as a bonus, it could be delivered by intravenous infusion. Treatment of alzheimer’s disease The Trials

There was a buzz of excitement in the air when I visited NeuroPhage’s offices in Cambridge, Massachusetts, in the summer of 2014. Meaning alzheimer disease The 18 staff, including Solomon, Hillerstrom, Fisher, and Krishnan, were hopeful that their new discovery, which they called the general amyloid interaction motif, or GAIM, platform, might change history. Information about alzheimer’s disease A decade after his mother had made her serendipitous discovery, Jonathan Solomon was finalizing a plan to get the product into the clinic. Symptoms of early onset alzheimer’s disease As Solomon says, “We now potentially have a drug that does everything that the phage could do, which can be delivered systemically and is easy to manufacture.”

Will it work in humans? While NPT088, being made up of large molecules, is relatively poor at penetrating the blood-brain barrier, the medicine persists in the body for several weeks, and so Fisher estimates that over time enough gets into the brain to effectively take out plaques. 10 early signs and symptoms of alzheimer disease The concept is that this antibody could be administered to patients once or twice a month by intravenous infusion for as long as necessary. Effects of alzheimer disease on the family “If our drug works, we will see it working in this trial.”

NeuroPhage must now navigate the FDA’s regulatory system and demonstrate that its product is safe and effective. Alzheimer disease and dementia journal impact factor So far, NPT088 has proved safe in nonhuman primates. Alzheimer’s disease cure But the big test will be the phase 1A trial expected to be under way this year. Medical definition alzheimer disease This first human study proposed is a single-dose trial to look for any adverse effects in healthy volunteers. Alzheimer’s disease define If all goes well, NeuroPhage will launch a phase 1B study involving some 50 patients with Alzheimer’s to demonstrate proof of the drug’s activity. Alzheimer’s disease society Patients will have their brains imaged at the start to determine the amount of amyloid-beta and tau. Cure for alzheimer’s disease Then, after taking the drug for six months, they will be reimaged to see if the drug has reduced the aggregates below the baseline.