Cause of ALS may be found, Northwestern team says… hmmm, keep up the research!

Dr. Teepu Siddique, a neurologist at Northwestern University's Feinberg School of Medicine, is a member of the team that discovered a common possible cause for all forms of ALS.

Drug ResearchScientific ResearchMedical ResearchNorthwestern UniversityAlzheimer's Disease

Researchers at Northwestern University say they have discovered a common cause behind the mysterious and deadly affliction of amyotrophic lateral sclerosis, or Lou Gehrig's disease, that could open the door to an effective treatment.

Dr. Teepu Siddique, a neuroscientist with Northwestern's Feinberg School of Medicine whose pioneering work on ALS over more than a quarter-century fueled the research team's work, said the key to the breakthrough is the discovery of an underlying disease process for all types of ALS.

The discovery provides an opening to finding treatments for ALS and could also pay dividends by showing the way to treatments for other, more common neurodegenerative diseases such as Alzheimer's, dementia and Parkinson's, Siddique said.

The Northwestern team identified the breakdown of cellular recycling systems in the neurons of the spinal cord and brain of ALS patients that results in the nervous system slowly losing its ability to carry brain signals to the body's muscular system.

Without those signals, patients gradually are deprived of the ability to move, talk, swallow and breathe.

"This is the first time we could connect (ALS) to a clear-cut biomedical mechanism," Siddique said. "It has really made the direction we have to take very clear and sharp. We can now test for drugs that would regulate this protein pathway or optimize it, so it functions as it should in a normal state."

The announcement of the breakthrough is in Monday's issue of the research journal Nature. The paper lists 23 contributing scientists, including the lead authors, Northwestern neurological researchers Han-Xiang Deng and Wenjie Chen, and Siddique as senior author.

ALS afflicts about 30,000 Americans. With no known treatment for the paralysis, 50 percent of all ALS patients die within three years.

It is particularly tragic because it often strikes people who are very physically active. In 1941, New York Yankee baseball superstar Lou Gehrig died at 37 of the disease that now carries his name.

Amelie Gubitz, a research program director at the National Institute of Neurological Disorders and Stroke, said the Northwestern research is a big step forward in efforts worldwide to conquer ALS.

"You need to understand at the cellular level what is going wrong," said Gubitz. "Then you can begin to design drugs.

"ALS is a complicated problem, and Dr. Siddique's research adds a big piece to the puzzle that gives us important new insights."

A variety of proteins perform different functions within cells, and Deng and Chen led research that discovered a key protein, ubiquilin2, in the ALS mystery.

Ubiquilin2 in spinal and brain system cells is supposed to repair or dispose of other proteins as they become damaged. The researchers discovered a breakdown of this function in ALS patients.

When Ubiquilin2 is unable to remove or repair damaged proteins, the damaged proteins begin to pile up in the cells, eventually blocking normal transmission of brain signals in the spinal cord and brain, leading to paralysis.

There are three forms of ALS: "familial," which is hereditary and passed through genes; nonhereditary, which is called "sporadic"; and ALS that targets the brain, called "ALS/dementia."

Siddique was part of a study that made a breakthrough in ALS in the early 1990s, discovering the "familial" gene that causes the disease within some families. That breakthrough came after he began an ongoing study 25 years ago of an East Coast family that has lost more than 20 members to ALS.

Joanne Saltzman, a 72-year-old member of that family, recalled last week how she first learned of ALS when she was a small girl and her father, a naval veteran, was dying of the disease. Her grandfather died of it, too, as did four of her father's seven brothers.

Subsequently, one of Saltzman's sisters and many of her cousins died from ALS. It killed her 51-year-old son last October, she said in a phone interview, and in February her 52-year-old niece died of it.

"I am so excited by their new findings," Saltzman said of the Northwestern study. "Dr. Siddique has been studying our family for 25 years, and it is so encouraging for our remaining family."

"I told Dr. Siddique's office, if I could cut off my arm and send it to them I would if it would help them in the research," she said. "I would do anything. It is so important to me to be able to find some kind of cure for this awful disease."

ALSA overwhelmed by Ice Bucket campaign :-)

In the couple of hours it took an official from the ALS Association to return a reporter's call for comment, the group's ubiquitous "Ice Bucket Challenge" had brought in a few million more dollars.

Approaching $110 million, the viral fundraising campaign for the ailment also known as Lou Gehrig's Disease has put the ALS group into the top ranks for medical charity donations. Since the end of July, the money has been sloshing in at a rate of about $9 million a week. Last year, from July 29 to Aug. 26, the group raised just $2.6 million.

It's caught everyone off guard, none more so than the ALS Association folks. But they know this is likely a one-off phenomenon, and the group now faces the task of spending all that money wisely. Research, care and advocacy are the group's three main missions - but officials say they don't know yet exactly how they'll use the astonishing windfall.

"I think even if I or any PR person at either a non-profit or a for-profit company had all of the PR dollars in the world to invest, no one would have come up with this idea," said Carrie Munk, the association's spokeswoman. "We realize there are responsibilities that come with being good stewards of these dollars."

Part of what's surprising is that ALS - or amyotrophic lateral sclerosis - is one of those "orphan" diseases. It is a neurodegenerative disease that causes paralysis and death, and the association estimates that about 5,600 new cases are diagnosed in the U.S. each year.

This campaign hasn't exactly put the charity in the same neighborhood as giants like the American Cancer Society, the American Heart Association or Susan G. Komen for the Cure - which raised $889 million, $529 million and $310 million last year, respectively. But it's moving into the same ZIP code now.

"People who have been in this space for a long period of time feel like it's a dream come true," says Munk.

In case you've been under the proverbial rock, here are the basic rules: Someone issues a challenge - that you allow yourself to be doused with a bucket of ice and water, like winning coaches along the sidelines. Then, the challengee has 24 hours to make a $100 donation to the ALS Association or submit to the water torture.

In the last month, everyone from Microsoft co-founder Bill Gates to former President George W. Bush has been doused. The Internet and airwaves are awash in videos of people taking the challenge - even if they fully intend to write the check.

Jonah Berger, author of the book "Contagious: Why Things Catch On," says it's like a modern-day chain letter - except, in this case, everyone will know if you break the chain.

"It has a lot of the key ingredients that often make people want to share things," said Berger, a marketing professor at the University of Pennsylvania's Wharton School. "It gives people lots of social currency to be part of it. It makes you look good. It makes you look smart and in the know - you know what's going on. And it's always hard to back down from a challenge."

And now others are co-opting the bucket challenge for their own causes.

Actor Matt Damon, for instance, dumped toilet water over his head to call attention to his passion - safe drinking water. Actor Orlando Jones of the television series "Sleepy Hollow" showered himself with bullets in the wake of black teenager Michael Brown's shooting death by a white police officer in Ferguson, Mo.

"I'm challenging myself to listen without prejudice, to love without limits and to reverse the hate," he said. "So that's my challenge - to me. And, hopefully, you'll accept this challenge, too."

The Chronicle of Philanthropy says the ALS Association has, in this short period of time, raised more than many of the charities included on its Philanthropy 400 list.

"Right now, we're really focused on reaching out to and acknowledging and thanking the over 2 million donors that have come to the ALS Association," said Munk, the association spokeswoman. "And also working to put a process in place to make the best decisions to spend these dollars."

The American Institute of Philanthropy's CharityWatch gave the group a B+ rating for spending about 73 percent of its cash budget on programs. Analyst Stephanie Kalivas has no reason to believe that rating will need to be downgraded.

"We will definitely be keeping an eye out for them," she said. "Hopefully, they won't be wasteful with it."

Dr. Richard Bedlack, who runs the ALS clinic at the Duke Institute for Brain Sciences in Durham, N.C., knows how he would allocate the money. While the temptation might be to plow it all into the search for a cure, he says the biggest strides have been made in patient care and quality of life, and that would be his No. 1 priority.

"The chances of one of these research studies really finding meaningful disease-modifying therapy is very small," he says. "We're shooting in the dark. So, of course we've got to keep trying. But the bottom line is we've got to understand this disease better before we're going to be able to fix it in most people."

Researchers discover how ALS spreads

A study led by University of British Columbia and Vancouver Coastal Health Research Institute researchers has revealed how the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is transmitted from cell to cell, and suggests the spread of the disease could be blocked.

"This work identifies an important piece of the puzzle in determining how the disease is transmitted throughout the nervous system," says lead investigator Dr. Neil Cashman, UBC's Canada Research Chair in Neurodegeneration and Protein Misfolding. "By understanding how this occurs, we can devise the best ways to stop the progressive neurological damage seen in ALS."

The research shows that misfolded non-mutant SOD1 can be transmitted from region to region in the nervous system, offering a molecular explanation for the progressive spread of ALS.

Published today in the Proceedings of the National Academy of Sciences, the study also shows the spread can be blocked using antibodies. Antibodies were specifically raised to bind to regions of SOD1 exposed when it is misfolded, and block its spread. If non-mutant SOD1 misfolding is the cause of ALS, as the study suggests, then the antibodies could arrest ALS progression, the researchers say.

This work builds on previous research in Cashman's lab. ALS is associated with the mutant SOD1 protein (superoxide dismutase 1) and earlier investigations found that the disease-associated mutant SOD1 can induce a change in the shape of other proteins at the molecular level by misfolding inside living cells. The affected proteins then accumulate in ways similar to the process underlying prion diseases – rare, fatal, degenerative brain disorders seen in both humans and animals.

ALS is a disease that affects nerve cells in the brain and the spinal cord. Motor neurons progressively degenerate and die so that the brain can no longer initiate and control muscle movement. Patients in the later stages of the disease may become totally paralyzed. There are approximately 140,000 new cases diagnosed worldwide each year.

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Background:

Dr. Neil Cashman is Professor and Canada Research Chair in Neurodegeneration and Protein Misfolding at UBC, and Academic Director of the Vancouver Coastal Health ALS Centre. He is also a member of the Brain Research Centre, a partnership between UBC and Vancouver Coastal Health Research Institute.

Prion disease:

Prion diseases belong to the general category of brain diseases called proteinopathies, which also includes Alzheimer's disease and Parkinson's disease. The most common human form of prion disease is Creutzfeldt-Jakob disease (CJD).

Prion diseases of animals include Bovine Spongiform Encephalopathy (BSE) (mad cow disease) in cattle, scrapie in sheep and goats, and Chronic Wasting Disease (CWD) in deer and elk.

Additional links:

Vancouver Coastal ALS Centre: http://www.vch.ca/403/7676/?program_id=952

Brain Research Centre: http://brain.ubc.ca

FDA okays start of BrainStorm stem cell trial in ALS patients

BrainStorm Cell Therapeutics said the U.S. Food and Drug Administration approved the start of a mid-stage clinical trial of its adult stem cell treatment for patients with amyotrophic lateral sclerosis (ALS).

The Phase II trial will be launched initially at Massachusetts General Hospital in Boston and the University of Massachusetts Memorial Hospital in Worcester.

Dana-Farber Cancer Institute's Connell O'Reilly Cell Manipulation Core Facility will manufacture BrainStorm's NurOwn cells for these two clinical sites. The trial will also be conducted at the Mayo Clinic, the Israel-based company said on Sunday. The trials are expected to start soon.

http://www.brainstorm-cell.com/index.php/science-a-technology/-nurown

"Today's announcement represents the most significant milestone BrainStorm has achieved to date," the company's president, Chaim Lebovits, said.

This trial will be the first Phase II double-blinded stem cell study to be conducted for ALS, he added.

ALS, also known as Lou Gehrig's Disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord.

BrainStorm's Phase II trial is designed to evaluate the safety and efficacy of transplantation of the stem cells in 48 ALS patients. The cells will be administered via intramuscular and intrathecal injection.

Patients will be followed monthly for three months before transplantation and for six months following transplantation.

Earlier clinical trials have shown that treatment with NurOwn cells was well tolerated and safe.

Last week, Cytokinetics Inc said its experimental treatment for Lou Gehrig's Disease failed the main goal in a mid-stage trial.

NEOWISE Finds Its First Comet On February 14

NEOWISE Finds Its First Comet On February 14

March 1, 2014

Image Caption: Comet NEOWISE was first observed by NASA's Near-Earth Object Wide-field Infrared Survey Explorer (NEOWISE) spacecraft on Valentine's Day, 2014. Credit: NASA/JPL-Caltech

NASA’s Near-Earth Object Wide-field Infrared Survey Explorer (NEOWISE) spacecraft has spotted a never-before-seen comet – its first such discovery since coming out of hibernation late last year.

“We are so pleased to have discovered this frozen visitor from the outermost reaches of our solar system,” said Amy Mainzer, the mission’s principal investigator from NASA’s Jet Propulsion Laboratory in Pasadena, Calif. “This comet is a weirdo – it is in a retrograde orbit, meaning that it orbits the sun in the opposite sense from Earth and the other planets.”

Officially named “C/2014 C3 (NEOWISE)”, the first comet discovery of the renewed mission came on Feb. 14 when the comet was about 143 million miles (230 million kilometers) from Earth. Although the comet’s orbit is still a bit uncertain, it appears to have arrived from its most distant point in the region of the outer planets. The mission’s sophisticated software picked out the moving object against a background of stationary stars. As NEOWISE circled Earth, scanning the sky, it observed the comet six times over half a day before the object moved out of its view. The discovery was confirmed by the Minor Planet Center, Cambridge, Mass., when follow-up observations were received three days later from the Near Earth Object Observation project Spacewatch, Tucson, Ariz. Other follow-up observations were then quickly received. While this is the first comet NEOWISE has discovered since coming out of hibernation, the spacecraft is credited with the discovery of 21 other comets during its primary mission.

Originally called the Wide-field Infrared Survey Explorer (WISE), the spacecraft was shut down in 2011 after its primary mission was completed. In September 2013, it was reactivated, renamed NEOWISE and assigned a new mission to assist NASA’s efforts to identify the population of potentially hazardous near-Earth objects. NEOWISE will also characterize previously known asteroids and comets to better understand their sizes and compositions.

JPL manages the NEOWISE mission for NASA’s Science Mission Directorate in Washington. The Space Dynamics Laboratory in Logan, Utah, built the science instrument. Ball Aerospace & Technologies Corp. of Boulder, Colo., built the spacecraft. Science operations and data processing take place at the Infrared Processing and Analysis Center at the California Institute of Technology in Pasadena. Caltech manages JPL for NASA.

More information on NEOWISE is online at: http://www.jpl.nasa.gov/wise/

ALS may be slowed by a diet rich in calories and carbohydrates…

A diet rich in calories and carbohydrates may slow progression of the lethal, degenerative Lou Gehrig's disease, according to a small-scale study reported in The Lancet on Friday.

PARIS: A diet rich in calories and carbohydrates may slow progression of the lethal, degenerative Lou Gehrig's disease, according to a small-scale study reported in The Lancet on Friday.

Formally called amyotrophic lateral sclerosis (ALS) or motor neuron disease, the disorder affects nerve cells that control muscle movement.

Patients become tired and weak and lose the power to move and eventually breathe; they die three years on average after being diagnosed.

The new study follows up on suspicions that ALS patients may be placed at even greater risk if they lose weight. They find it hard to eat and swallow, and eventually have to be fed with a tube directly into the stomach.

Experiments on mice genetically engineered to display ALS symptoms have found that those given a high-calorie diet rich in fat survived longer.

Building on this work, researchers in the United States tested 20 volunteers with advanced ALS who were at the stage of being tube-fed.

The patients were divided into three groups.

One was a "control" group which received a nutritional formula designed to keep their weight stable, while the other two received 125 percent of the calories they needed to maintain their weight.

Of these two groups, one received a high-calorie diet rich in carbohydrates, and the other a high-calorie diet rich in fats.

The diets lasted for four months, and patients were followed for a further five months afterwards.

Patients on the diet that was high in calories and carbs did far better than counterparts in the two other groups, the researchers found.

They experienced fewer "adverse events" -- health problems ranging from pneumonia to muscular pains or rashes.

They also gained more weight, picking up 390g per month on average, compared to a gain of 110g in the control group and a loss of 460g in the high-calorie high-fat diet group.

During the five-month follow-up, no deaths occurred among the high-calorie, high-carbohydrate group, compared with one in the high-fat group and three in the control group, said the study.

The experiment was only conducted on a small scale and its chief goal had been to see whether ALS patients could safely change diet, rather than testing how effective the switch might be.

"This pilot study demonstrates the safety of a novel, simple, low-cost treatment for a devastating disease where currently very few treatment options are available," said lead researcher Anne-Marie Wills at the Massachusetts General Hospital in Boston.

"The adverse outcomes that we feared might result from weight gain, such as diabetes or heart disease, were not observed in our study period."

The team called for larger trials among patients at an earlier stage of ALS, to see whether these optimistic but cautious findings hold true.

My Program from Ball Aerospace is Reignited

WISE reactivated to hunt for asteroids

I worked on this spacecraft during my years at Ball as the Mission Assurance Manager. That’s me with WISE on the right.

The spacecraft will assist in efforts to identify the population of potentially hazardous near-Earth objects, as well as those suitable for asteroid exploration missions.

 

This artist's concept shows the Wide-field Infrared Survey Explorer (WISE) spacecraft in its orbit around Earth. In September of 2013, engineers will attempt to bring the mission out of hibernation to hunt for more asteroids and comets in a project called NEOWISE.

A NASA spacecraft that discovered and characterized tens of thousands of asteroids throughout the solar system before being placed in hibernation will return to service for three more years starting in September, assisting the agency in its effort to identify the population of potentially hazardous near-Earth objects, as well as those suitable for asteroid exploration missions.
The Wide-field Infrared Survey Explorer (WISE) will be revived next month with the goal of discovering and characterizing near-Earth objects (NEOs), space rocks that can be found orbiting within 28 million miles (45 million kilometers) of Earth’s path around the Sun. NASA anticipates WISE will use its 16-inch (40 centimeters) telescope and infrared cameras to discover about 150 previously unknown NEOs and characterize the size, albedo, and thermal properties of about 2,000 others, including some that could be candidates for the agency’s recently announced asteroid initiative.
“The WISE mission achieved its mission’s goals and as NEOWISE extended the science even further in its survey of asteroids. NASA is now extending that record of success, which will enhance our ability to find potentially hazardous asteroids and support the new asteroid initiative,” said John Grunsfeld, NASA’s associate administrator for science in Washington, D.C. “Reactivating WISE is an excellent example of how we are leveraging existing capabilities across the agency to achieve our goal.”
NASA’s asteroid initiative will be the first mission to identify, capture, and relocate an asteroid. It represents an unprecedented technological feat that will lead to new scientific discoveries and technological capabilities that will help protect our home planet. The asteroid initiative brings together the best of NASA’s science, technology, and human exploration efforts to achieve President Obama’s goal of sending humans to an asteroid by 2025.
Launched in December 2009 to look for the glow of celestial heat sources from asteroids, stars, and galaxies, WISE made about 7,500 images every day during its primary mission from January 2010 to February 2011. As part of a project called NEOWISE, the spacecraft made the most accurate survey to date of NEOs. NASA turned most of WISE’s electronics off when it completed its primary mission.
“The data collected by NEOWISE two years ago have proven to be a gold mine for the discovery and characterization of the NEO population,” said Lindley Johnson, NASA’s NEOWISE program executive in Washington, D.C. “It is important that we accumulate as much of this type of data as possible while the WISE spacecraft remains a viable asset.”
Because asteroids reflect but do not emit visible light, infrared sensors are a powerful tool for discovering, cataloging, and understanding the asteroid population. Depending on an object’s reflectivity, or albedo, a small light-colored space rock can look the same as a big dark one. As a result, data collected with optical telescopes using visible light can be deceiving.
During 2010, NEOWISE observed about 158,000 rocky bodies out of approximately 600,000 known objects. Discoveries included 21 comets, more than 34,000 asteroids in the main belt between Mars and Jupiter, and 135 near-Earth objects.
The WISE prime mission was to scan the entire celestial sky in infrared light. It captured more than 2.7 million images in multiple infrared wavelengths and cataloged more than 560 million objects in space, ranging from faraway galaxies to asteroids and comets much closer to Earth.
“The team is ready, and after a quick checkout, we’re going to hit the ground running,” said Amy Mainzer from NASA’s Jet Propulsion Laboratory in Pasadena, California. “NEOWISE not only gives us a better understanding of the asteroids and comets we study directly, but it will help us refine our concepts and mission operation plans for future space-based near-Earth object cataloging missions.”

By Jet Propulsion Laboratory, Pasadena, California, NASA Headquarters, Washington, D.C. — Published: August 22, 2013