View Full Version : Nanotechnology and Immune-related Diseases

11-18-2012, 11:05 PM
Breakthrough Nanoparticle Halts Multiple Sclerosis in Mice, Offers Hope for Other Immune-Related Diseases

ScienceDaily (Nov. 18, 2012) — In a breakthrough for nanotechnology and multiple sclerosis, a biodegradable nanoparticle turns out to be the perfect vehicle to stealthily deliver an antigen that tricks the immune system into stopping its attack on myelin and halt a model of relapsing remitting multiple sclerosis (MS) in mice, according to new Northwestern Medicine research.

The new nanotechnology also can be applied to a variety of immune-mediated diseases including Type 1 diabetes, food allergies and airway allergies such as asthma.

In MS, the immune system attacks the myelin membrane that insulates nerves cells in the brain, spinal cord and optic nerve. When the insulation is destroyed, electrical signals can't be effectively conducted, resulting in symptoms that range from mild limb numbness to paralysis or blindness. About 80 percent of MS patients are diagnosed with the relapsing remitting form of the disease.

Nanoparticles Fool Immune System
In the study, researchers attached myelin antigens to the nanoparticles and injected them intravenously into the mice. The particles entered the spleen, which filters the blood and helps the body dispose of aging and dying blood cells. There, the particles were engulfed by macrophages, a type of immune cell, which then displayed the antigens on their cell surface. The immune system viewed the nanoparticles as ordinary dying blood cells and nothing to be concerned about. This created immune tolerance to the antigen by directly inhibiting the activity of myelin responsive T cells and by increasing the numbers of regulatory T cells which further calmed the autoimmune response.

Breakthrough nanoparticle halts multiple sclerosis in mice (http://www.sciencedaily.com/releases/2012/11/121118141516.htm)

Seriously cool stuff.

06-10-2016, 05:00 AM
Canadian doctors reverse severe MS using stem cells...
This isn’t hype: Canadian doctors just reversed severe MS using stem cells
June 9, 2016 - The multiple lives of MS patient Jennifer Molson — after her chemotherapy treatment

Jennifer Molson was 21, juggling a day job and night school to pursue her dream of becoming a cop, when she was diagnosed with multiple sclerosis. She woke up one morning with pins and needles in her hand, and within a week she couldn't move her left arm. By 2001, five years later, she was living in the Ottawa Hospital under 24-hour care, getting around using a cane, walker, or wheelchair. When she was discharged on weekends, to spend time with her then-boyfriend Aaron, she had to rely on him for her every need. He'd cut her food into bite-size pieces, and bathe and dress her. When she lost control of her bladder or bowel, he'd help her go to the bathroom. "I had no feeling from the chest down," Molson says. "I could touch something boiling on the stove and burn myself. I could touch fabric without knowing whether it's sandpaper." For patients like Molson, with a severe form of MS and no response to the available medications, there’s little hope.


Two years later, her life had taken an abrupt turn. "I walked down the aisle and danced at my wedding, something I had always dreamed of doing," she said of her marriage to Aaron in 2003. Now, 15 years later, Molson is still skiing and kayaking on the weekends. She works as a research assistant at Ottawa Hospital. What happened is something even esteemed medical specialists are venturing to call a "miracle": The particularly aggressive MS that was on track to disable Molson entirely — and potentially kill her — is now virtually eliminated from her body. The game changer for Molson was a chemotherapy and stem cell bone marrow transplant she got in 2002 as part of a study in Canada. Molson was one of a small cohort of 24 people with MS who received the high-risk, experimental therapy. Of the 24 patients, 70 percent saw the progression of their disease halted or reversed.


Their experience, documented in a paper published today in the Lancet, is the first to describe any MS treatment that fully stops the disease over the long term without MS medication. "Everyone is hesitating to use the 'c word,' but these patients are cured," says Michael Rudnicki, director of the Regenerative Medicine Program and the Sprott Centre for Stem Cell Research at the Ottawa Health Research Institute, who was not involved with the research. "Jennifer Molson was in a wheelchair in a rehab center unable to work. And now she's skiing, she's working, she got married, got her driver's license. I think this is going to be the new standard of care for progressive MS."

MORE (http://www.vox.com/2016/6/9/11898512/multiple-sclerosis-stem-cell-chemo)

08-18-2016, 06:54 PM
Finding the roots of disease...
DNA catalogue helping find roots of disease
Fri, Aug 19, 2016 - ADVANTAGES: A genetics expert not involved in the new work said there is little doubt it will help accelerate and refine the search for the causes of many diseases

A huge catalogue of human DNA is helping researchers find tiny glitches that cause disease, in part by pointing out some false leads. The database, with genetic codes from more than 60,000 people, is aimed at researching rare diseases that are generally caused by a single malfunctioning gene. Most of these diseases are so uncommon that the general public has never heard of them, but there are thousands of such conditions, and as a group they affect about 1 percent of births. Better accuracy in identifying the genetic cause of a person’s disease provides a “clear and direct benefit to patients,” said Daniel MacArthur of the Broad Institute in Cambridge, Massachusetts, and Massachusetts General Hospital in Boston.

He is senior author of an analysis published on Wednesday in the journal Nature by researchers who compiled the database, which draws on DNA data from more than two dozen disease studies. It went online in 2014 and has since been consulted more than 5 million times, he said. For rare diseases, doctors try to find the genetic cause by analyzing the patient’s DNA. However, everybody carries tens of thousands of minute differences from the standard DNA code, and the goal is to find which one or two of them is making the person sick. Researchers frequently do that through guilt by association. If a variation shows up in a patient, but it is never seen or extremely rare in others, it might be fingered as the cause of disease.

The challenge is getting enough DNA from the general public. If the sampling is too small or not comprehensive enough for diverse populations, a variant might be wrongly blamed as the cause of the patient’s problems. A better sampling might show the variant actually appears in healthy people often enough that it is clearly not making anybody sick. False leads can harm patient care, including in some cases missing out on treatments, MacArthur said. An example of such a “genetic misdiagnosis” was presented on Wednesday in an unrelated study in the New England Journal of Medicine. It focused on an inherited disease called hypertrophic cardiomyopathy, which thickens the heart muscle and can interfere with pumping blood.

Examining three years of records from a testing lab, it found that seven patients were told they carried one of two DNA variants that had been linked to the heart disease. Both variants were later reclassified as benign. At least five of the patients were of African ancestry. If the original studies of those variants had included enough black Americans in their samples, they probably would not have reached the wrong conclusion, the Harvard researchers said. They said the new DNA catalogue, dubbed ExAC, is well-equipped to avoid such errors. It provides a far more comprehensive collection of DNA variations than has been available in the past. The roughly 10 million tiny variations listed are from people of European, African, South Asian, East Asian and Latino ancestry.

MORE (http://www.taipeitimes.com/News/world/archives/2016/08/19/2003653443)

08-25-2016, 10:35 PM
Speeding blood clotting with nanoparticles...
Newly Developed Nanoparticles Speed Blood Clotting
August 24, 2016 - Researchers are working to develop nanoparticles that could speed blood clotting and potentially save lives.

Blunt force trauma, stab wounds and gunshot wounds can all cause life-threatening internal bleeding. And for soldiers in wartime, more and more are returning with internal bleeding linked to traumatic brain injuries, or TBIs, caused by roadside bombs, according to Erin Lavik, a researcher at the University of Maryland in Baltimore. Surgery is the most common method used to stop hemorrhaging and prevent death. "One of the things about hemorrhaging is you can bleed a lot and be fine,” Lavik said, “but then there's a tipping point where, if you bleed past a certain point, it's suddenly lethal."

A number of research teams are working to develop agents that can help speed blood clotting. Lavik and his colleagues are using nanoparticles — microscopic particles that are part of a protein complex in the body — that act as bridges to platelets, which are blood fragments that rush to the site of an injury to stop bleeding. The nanoparticles, which are delivered intravenously, stick to the platelets, activating them quickly so they join together to hasten the formation of clots. After the bleeding has stopped, the particles clear the system.

An Afghan soldier and a U.S. soldier were injured by a roadside bomb blast, Sept. 18, 2010. Such blasts can cause to traumatic brain injuries and internal bleeding. Researchers are looking at ways to better treat such injuries.

The researchers tested the nanoparticles in rats. One test simulated bleeding from a blast shock that often causes injuries in hollow internal organs, such as the lungs. A test on the liver, a blood-rich organ that can be ruptured by a blow to the abdomen, showed that nanoparticles look promising in stanching the bleeding. The researchers are also looking at nanoparticles as a way to minimize bleeding in brain and spinal cord injuries, as well. Lavik presented the work at the annual meeting of the American Chemical Society.

Human trials will be conducted to make sure the nanoparticles don't trigger a harmful immune response. Another concern is that the nanoparticles could worsen clotting in the legs or lungs, which can be deadly. Lavik estimates it could take five to ten years for a nanoparticle treatment to be ready to administer in hospital emergency rooms or combat zones.


04-18-2017, 12:43 AM
Macrophages apparently can harbor HIV...

Second Immune Cell Found to Harbor HIV During Treatment
April 17, 2017 - The challenge of finding a cure for AIDS may have gotten harder. Scientists have discovered another cell in the body where HIV — the virus that causes AIDS — hides from therapy designed to suppress it to undetectable levels in the blood.

The cells — called macrophages — are part of the immune system and are found throughout the body, including in the liver, lungs, bone marrow and brain. After other immune cells have done their job of destroying foreign invaders, these large white blood cells act as the cleanup crew. They surround and clean up cellular debris, foreign substances, cancer cells and anything else that is not essential to the functioning of healthy cells. In addition, they apparently can harbor HIV.

A new target

While antiretroviral drugs can drive the AIDS virus down to virtually undetectable levels, scientists know if therapy is interrupted, an HIV infection can come roaring back. That's because of a viral reservoir that until now has been thought only to inhabit immune system T-cells — the cells that are attacked and destroyed by the AIDS virus. Much research is dedicated to trying to find ways to eradicate the T-cell reservoir. This may mean researchers must find ways to eliminate HIV from macrophages, as well. The finding was published in Nature Medicine by researchers in the Division of Infectious Diseases at the University of North Carolina School of Medicine.

A Cambodian health agent pricks the finger of a woman who sought an HIV blood test service in Peam village, Muk Kompoul district, Kandal province,

Investigators demonstrated in a mouse model that in the absence of humanized T-cells, antiretroviral drugs could strongly suppress HIV in macrophages. However, when the therapy was interrupted, the virus rebounded in one-third of the mice. This, say researchers, is consistent with persistent infection in the face of drug therapy. Researchers say their work demonstrates that any possible therapies must address macrophages in addition to T-cells to eradicate viral reservoirs. Investigators say they now have more information pointing to the complexity of the virus, and that targeting the viral reservoir in T-cells in the blood will not necessarily work with tackling HIV persistence in macrophages, which reside in tissues and are harder to observe.

Senior author Victor Garcia said it’s possible there are other HIV reservoirs still to be discovered. The lead author of the study, Jenna Honeycutt, called the discovery "paradigm changing" in the way scientists must now try to eliminate persistent infection in HIV-positive individuals. Investigators say their next step is to figure out what regulates HIV persistence in infected macrophages. They are also interested in finding HIV interventions that completely eradicate the AIDS virus from the body.

Second Immune Cell Found to Harbor HIV During Treatment (http://www.voanews.com/a/second-immune-cell-harbor-hiv-during-treatment/3813340.html)

See also:

Scientists Tout Possible Cure for HIV Infection
April 12, 2017 - Scientists are touting a discovery that they think might cure HIV infection. They’ve engineered an antibody that blocks the virus from entering and infecting key immune system cells.

The process, developed at the Scripps Researcher Institute in California, involves tethering an antibody, which fights infection, directly onto T cells, the immune system cells that are targeted by the AIDS virus. Eventually, if enough immune cells become infected and destroyed by HIV, the disease progresses to AIDS, which leads to certain death. The antibodies, however, block the receptor on the T cells that HIV uses to enter and destroy them. It’s what immunochemist Richard Lerner called a form of "cellular vaccination." He said the genetic alteration of the T cells with tethered antibodies does not interfere with the immune cells' ability to fight other pathogens.

Lerner is the senior author of a study describing the work in Proceedings of the National Academy of Sciences. Experimental HIV vaccines attempt to stimulate an immune response, creating HIV-specific antibodies to attack and destroy infected cells. But Lerner says the concentration of antibodies flowing freely in the bloodstream is too low to reach every infected T cell.

‘Survival of the fittest’

This approach is different, protecting only some healthy T cells. "You don’t really care about the rest of the body," Lerner explained. "You would just like to shield those cells from viruses and a virus attack. So that’s the chemical principle. Never mind immunizing the whole body. Just immunize the cells that are the real victims." His team added a gene to T cells which instructed them to synthesize antibodies that would bind with the cellular receptor called CD4. That is the doorway to the cell for HIV. Having antibodies hanging on to the cell surface blocks that doorway. It's hoped that eventually in humans, these HIV-resistant cells will multiply into the millions, passing on the protective gene, as the unprotected, infected cells die off, eradicating the AIDS virus from the body and affording a long-lasting cure.

A scientist works with a laboratory petri dish. Scientists have engineered an antibody that blocks the HIV virus from entering and infecting key immune system cells.

At least that’s what experiments in the laboratory suggested when both genetically engineered and unprotected human T cells were exposed to HIV. Lerner said the engineered T cells would be introduced into a patient’s bone marrow, which would produce protective cells en masse. "We hope to, after securing their safety and so on and so forth, in a patient with HIV, [the engineered cells] can harm their [infected] cells with [the] resistance of ours, and ... hopefully the good cells will be selected over the bad cells. And that will be the end of HIV in that patient," Lerner said.

It's an approach that Lerner calls a Darwinian "survival of the fittest." Scripps investigators are working with City of Hope, an independent research and comprehensive cancer treatment center in Duarte, California, that has a lot of experience with bone marrow transplantation. The center will carry out clinical trials of the engineered, HIV-resistant T cells with an eye toward advancing what scientists hope will be a cure for AIDS.