ALS Researchers Uncover New Insights Into Motor Neuron Death in Lou Gehrig’s Disease

ALS Researchers Uncover New Insights Into Motor Neuron Death in Lou Gehrig’s Disease
Posted by: Susan Ardizzoni March 31, 2014

Current research at The Institute at Nationwide Children’s Hospital has revealed information about a key player in motor neuron death in Amyotrophic lateral sclerosis (ALS) otherwise known as Lou Gehrig’s disease. The researchers believe this to be a key step in developing a treatment.

ALS involves a cascade of cellular and inflammatory events that weakens and kill motor neurons in the brain and spinal column. The motor neuron destruction is a complex process that involves cells that normally protect neurons from harm. These motor neurons control the function of muscles throughout the body. As the motor neurons die, muscles begin to weaken. Individuals with ALS eventually lose their ability to move, and with further progression they are unable to breathe on their own. Within 3 to 5 years of onset, most ALS patients die from respiratory failure.

Researchers took a look at a protein that is involved in transcriptional regulation known as nuclear factor-kappa B (NF-κB). This protein is involved with the neuro-inflammatory response that is common in ALS, and it has also been linked to cancer and a number of other inflammatory and autoimmune diseases.

The study examined ALS progression in mice where NF-κB was inhibited in astrocytes and microglia. These two cell types are the first and main form of defense against pathogens in the brain and spinal column. According to Brian Kaspar, MD, a principal investigator in the Center for Gene Therapy at Nationwide Children’s and senior author of the new study, inhibiting NF-κB in microglia decreased ALS progression by 47 percent. “ The field has identified different cell types in addition to motor neurons involved in this disease, so one of our approaches was to find out what weapons these cells might be using to kill motor neurons. And our findings suggest that the microglia utilize an NF-κB-mediated inflammatory response as one of its weapons.”

Researchers report that inhibiting NF-κB in astrocytes had no effect on ALS progression so the search for weapons that astrocytes use against motor neurons still continues. How or why NF-κB causes microglia to turn into neuron-killing agents still remains a mystery, however the current study moves researchers closer to finding therapy for ALS.

Current research at The Institute at Nationwide Children’s Hospital has revealed information about a key player in motor neuron death in Amyotrophic lateral sclerosis (ALS) otherwise known as Lou Gehrig’s disease. The researchers believe this to be a key step in developing a treatment.

ALS involves a cascade of cellular and inflammatory events that weakens and kill motor neurons in the brain and spinal column. The motor neuron destruction is a complex process that involves cells that normally protect neurons from harm. These motor neurons control the function of muscles throughout the body. As the motor neurons die, muscles begin to weaken. Individuals with ALS eventually lose their ability to move, and with further progression they are unable to breathe on their own. Within 3 to 5 years of onset, most ALS patients die from respiratory failure.

Researchers took a look at a protein that is involved in transcriptional regulation known as nuclear factor-kappa B (NF-κB). This protein is involved with the neuro-inflammatory response that is common in ALS, and it has also been linked to cancer and a number of other inflammatory and autoimmune diseases.

The study examined ALS progression in mice where NF-κB was inhibited in astrocytes and microglia. These two cell types are the first and main form of defense against pathogens in the brain and spinal column. According to Brian Kaspar, MD, a principal investigator in the Center for Gene Therapy at Nationwide Children’s and senior author of the new study, inhibiting NF-κB in microglia decreased ALS progression by 47 percent. “ The field has identified different cell types in addition to motor neurons involved in this disease, so one of our approaches was to find out what weapons these cells might be using to kill motor neurons. And our findings suggest that the microglia utilize an NF-κB-mediated inflammatory response as one of its weapons.”

Researchers report that inhibiting NF-κB in astrocytes had no effect on ALS progression so the search for weapons that astrocytes use against motor neurons still continues. How or why NF-κB causes microglia to turn into neuron-killing agents still remains a mystery, however the current study moves researchers closer to finding therapy for ALS.

Current ALS research is focused in two directions. One path is trying to determine the trigger that leads to ALS onset. The other path is trying to understand the process that leads to ALS progression. It is known that changes in motor neurons leads to ALS onset, however disease progression appears to be determined by alterations to astrocytes, microglia and oligodendrocytes. Most cases of ALS have no family ties to the disease, however some cases are hereditary. Due to the complexity of ALS and the lack of familiar tie, screening before onset is practically impossible.

According to Kaspar, “Focusing on stopping the changes that occur in astrocytes and microglia has clinical relevance because most people don’t know they’re getting ALS. We have identified a pathway in microglia that may be targeted to ultimately slow disease progression in ALS and are exploring potential therapeutic strategies and may have broader implications for diseases such as Alzheimer’s and Parkinson’s Disease amongst others.”

New Technique Generates ALS-Derived Muscle for study…

New Technique Generates ALS-Derived Muscle for Study

Washington, D.C. (March 25, 2014) — In work supported by The ALS Association, scientists have developed a new method for generating muscle cells from skin tissue of people with ALS, which will be valuable for research. The study was published in the journal Stem Cells Translational Medicine.
ALS (amyotrophic lateral sclerosis), also known as Lou Gehrig’s Disease, is a progressive neurodegenerative disease that affects neurons (nerve cells) in the brain and the spinal cord. Eventually, people with ALS lose the ability to initiate and control muscle movement, which often leads to total paralysis and death within two to five years of diagnosis. There is no cure and no life-prolonging treatments for the disease.

The scientific team was led by Masatoshi Suzuki, Ph.D., D.V.M., of the University of Wisconsin at Madison, and included Allison Ebert, Ph.D., of the Medical College of Wisconsin. Their work was supported by the Wisconsin Chapter of The ALS Association.

The researchers showed that muscle progenitor cells could be efficiently produced from stem cells in cell culture, using a new combination of growth factors. The method works with either human embryonic stem cells or induced pluripotent stem cells (iPS cells), which are derived from skin cells. In the study, the researchers transformed iPS cells from two different people with familial forms of ALS, one caused by mutations in the SOD1 gene and the other by mutations in the VAPB gene.
“The ability to generate muscle cells from ALS-related tissue is important, because we need to understand more about the role of muscle in the disease process,” said Lucie Bruijn, Ph.D., MBA, Chief Scientist for The Association. “We know an early step in ALS is loss of contact between muscle and motor neuron. This system should allow us to determine more about that important step and determine whether, if we can delay it, we can prolong both neuron health and muscle function.”

About The ALS Association
The ALS Association is the only national non-profit organization fighting Lou Gehrig’s Disease on every front. By leading the way in global research, providing assistance for people with ALS through a nationwide network of chapters, coordinating multidisciplinary care through certified clinical care centers, and fostering government partnerships, The Association builds hope and enhances quality of life while aggressively searching for new treatments and a cure. For more information about The ALS Association, visit our website at http://www.alsa.org.

Wishing you all love, light, and blessings…

Hi Everyone,

We wanted to reach out and say a quick hello to all. We appreciate all of your continued support as crusaders of ALS regarding research, getting the word out about ALS, and ultimately helping us raise awareness and funds to find a cure for ALS once and for all! We will be continuing our Steffen Crusade in honor of my father Don Steffen and will keep you all up to speed with the different things we are doing.

Stay tuned in! We are already in planning stages for the next Don Steffen Annual Charity Golf Tournament for ALS.

All the best,

The Steffens

The ALS Association Announces $4.3 Million in Research Grants for Global Fight Against ALS

The ALS Association Announces $4.3 Million in Research Grants for Global Fight Against ALS
August 13, 2013

The ALS Association announced today that it has awarded $4.3 million in new research grants. These awards are part of its Translational Research Advancing Therapy (TREAT ALS ™) program, through which The Association funds a diverse portfolio of amyotrophic lateral sclerosis (ALS) research to find treatments and a cure for the disease.

“These awards will drive research on several emerging fronts in the quest to understand and find treatments for ALS,” said Lucie Bruijn, Ph.D., Chief Scientist for The ALS Association. “The generosity of our donors and supporters makes these grants possible. We are very grateful for that generosity and the opportunity it provides to make these awards for this important research.”

The awards will go to scientists in laboratories in 14 states in the United States as well as in the United Kingdom, Ireland, Belgium, Canada, Argentina, France and Italy. These awards will support 35 new research projects.

Financial support from the following organizations and individuals enabled The ALS Association to fund these new research grants: Greater Philadelphia Chapter; Greater New York Chapter; The Jeff Kaufman Fund of the Wisconsin Chapter; Greater Chicago Chapter; Texas Chapter; Golden West Chapter; Greater Sacramento Chapter; Orange County Chapter; Greater San Diego Chapter; The Motor Neuron Disease Association of the United Kingdom; and Jay and Toshiko Tompkins.

The ALS Association funds both Investigator-Initiated Awards, for research proposed by investigators and Association-Initiated Awards, for research proposals in areas identified by The Association and its scientific advisors as key targets for new research.

The Association also offers The Milton Safenowitz Postdoctoral Fellowship for ALS Research Award. Founded by the Safenowitz family through the Greater New York Chapter of The ALS Association and in memory of Mr. Safenowitz, who died of ALS in 1998, these awards are to encourage and facilitate promising young scientists to enter the ALS field.

The Association is also continuing major support for the Northeast ALS Consortium (NEALS), to support the TREAT ALS NEALS Clinical Trials Network.

All of these new grants will support research to understand the causes of ALS, to develop new treatments, and to create tools that will help improve clinical trials of new therapies. More specifically, the research will include animal model systems, genetics, stem cells, and work directly with people with ALS.

Thank you for your support at the Don’s Steffen Charity ALS Golf Tournament

Hi Everyone,

I wanted to take a moment to thank all of you that attended or showed your support in one way or the other in memory or as I like to say in “HONOR” of my dad Don Steffen. This tournament is important to my family and has been promised by us, to my father, to continue his legacy to help asssist in finding a cure for ALS through awareness and raising funds. If we can help one person, we have done our job, if we can help assist in putting ALS out of business, we have won the battle by helping to find a cure!

The tournament allows all of us to celebrate my dad and help those in need that are going through any stage of ALS for the patient, the caregivers, and the family and friends of those affected in any way shape or form by ALS.

We are in the process of tallying the funds raised at the Don Steffen Charity ALS Tournamanet and will have news to share soon!

Love, light, and blessings to you all!

Angela and the Steffen family!

National ALS Advocacy Days in Washington DC

National ALS Advocacy Days in Washington DC

If you have a few minutes today, call or email your Senators and Congressmen and let them know you support continued funding of the National ALS Registry at $10 million, and the Department of Defense’s ALS Research Program at $10 million. These are important programs that will help us understand and find better treatments for this dreaded disease and they are constantly in jeopardy of being cut in these difficult financial times.

ALS Untangled No. 20: The Deanna Protocol

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