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Major ALS breakthrough (and Alzheimer's?)
Northwestern University ^ | August 21, 2011 | Unknown

Posted on 08/21/2011 1:27:07 PM PDT by decimon

Researchers discover common cause of all forms of ALS

CHICAGO --- The underlying disease process of amyotrophic lateral sclerosis (ALS and Lou Gehrig's disease), a fatal neurodegenerative disease that paralyzes its victims, has long eluded scientists and prevented development of effective therapies. Scientists weren't even sure all its forms actually converged into a common disease process.

But a new Northwestern Medicine study for the first time has identified a common cause of all forms of ALS.

The basis of the disorder is a broken down protein recycling system in the neurons of the spinal cord and the brain. Optimal functioning of the neurons relies on efficient recycling of the protein building blocks in the cells. In ALS, that recycling system is broken. The cell can't repair or maintain itself and becomes severely damaged.

The discovery by Northwestern University Feinberg School of Medicine researchers, published in the journal Nature, provides a common target for drug therapy and shows that all types of ALS are, indeed, tributaries, pouring into a common river of cellular incompetence.

"This opens up a whole new field for finding an effective treatment for ALS," said senior author Teepu Siddique, M.D., the Les Turner ALS Foundation/Herbert C. Wenske Professor of the Davee Department of Neurology and Clinical Neurosciences at Northwestern's Feinberg School and a neurologist at Northwestern Memorial Hospital. "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 discovery of the breakdown in protein recycling may also have a wider role in other neurodegenerative diseases, specifically the dementias. These include Alzheimer's disease and frontotemporal dementia as well as Parkinson's disease, all of which are characterized by aggregations of proteins, Siddique said. The removal of damaged or misfolded proteins is critical for optimal cell functioning, he noted.

This breakdown occurs in all three forms of ALS: hereditary, which is called familial; ALS that is not hereditary, called sporadic; and ALS that targets the brain, ALS/dementia.

In related research, Feinberg School researchers also discovered a new gene mutation present in familial ALS and ALS/dementia, linking these two forms of the disease.

Siddique has been searching for the causes and underlying mechanism of ALS for more than a quarter century. He said he was initially drawn to it because, "It was one of the most difficult problems in neurology and the most devastating, a disease without any treatment or known cause."

Siddique's efforts first showed in 1989 that molecular genetics techniques were applicable to ALS, then described the first ALS gene locus in 1991, which led to the discovery of SOD1 and engineering of the first genetic animal model for ALS.

ALS affects an estimated 350,000 people worldwide, including children and adults, with about 50 percent of people dying within three years of its onset. In the motor disease, people progressively lose muscle strength until they become paralyzed and can no longer move, speak, swallow and breathe. ALS/dementia targets the frontal and temporal lobes of the brain, affecting patients' judgment, the ability to understand language and to perform basic tasks like planning what to wear or organizing their day.

"These people in the prime of their lives and the peak of their productivity get this devastating illness that kills them," Siddique said. "The people who get ALS/dementia, an even more vicious disease, have a double whammy."


Feinberg School scientists found the cause of ALS by discovering a protein, ubiquilin2, whose critical job is to recycle damaged or misfolded proteins in motor and cortical neurons and shuttle them off to be reprocessed.

In people with ALS, Feinberg researchers found ubiquilin2 isn't doing its job. As a result, the damaged proteins and ubiquilin2 loiter and accumulate in the motor neurons in the spinal cord and cortical and hippocampal neurons in the brain. The protein accumulations resemble twisted skeins of yarn -- characteristic of ALS -- and cause the degeneration of the neurons.

Researchers found ubiquilin2 in these skein-like accumulations in the spinal cords of ALS cases and in the brains of ALS/dementia cases.

The scientists also discovered mutations in ubiquilin2 in patients with familial ALS and familial ALS/dementia. But the skein-like accumulations were present in people's brains and spinal cords in all forms of ALS and ALS/dementia, whether or not they had the gene mutation.

"This study provides robust evidence showing a defect in the protein degradation pathway causes neurodegenerative disease," said Han-Xiang Deng, M.D., lead author of the paper and associate professor of neurology at the Feinberg School. "Abnormality in protein degradation has been suspected, but there was little direct evidence before this study." The other lead author is Wenjie Chen, senior research technologist in neurology.


About 90 percent of ALS is sporadic, without any known cause, until this study. The remaining 10 percent is familial. To date, mutations in about 10 genes, several of which were discovered at Northwestern, including SOD1 and ALSIN, account for about 30 percent of classic familial ALS, noted Faisal Fecto, M.D., study co-author and a graduate student in neuroscience at Feinberg.

TOPICS: Health/Medicine; Science
KEYWORDS: als; alzheimers; amyotrophic; dementia; lateral; sclerosis

1 posted on 08/21/2011 1:27:13 PM PDT by decimon
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To: neverdem; DvdMom; grey_whiskers; Ladysmith; Roos_Girl; Silentgypsy; conservative cat; ...


2 posted on 08/21/2011 1:28:21 PM PDT by decimon
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To: decimon

Hopefully, this potential cure won’t result in the apes (or other mutants) taking over the planet.

3 posted on 08/21/2011 1:34:20 PM PDT by rbg81
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To: decimon

Prayers this is the beginning of the end of ALS sufferings. Had a lovely Aunt, and of course the entire family suffer her slow, and excrutiating demise due ALS. It was terrible.

4 posted on 08/21/2011 1:46:31 PM PDT by rockinqsranch (Dems, Libs, Socialists, call 'em what you will, they ALL have fairies livin' in their trees.)
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To: decimon

I have a very close friend who is dying of ALS. It is a horrible way to die. I hope this really leads to a treatment, as there is nothing now.

5 posted on 08/21/2011 1:47:27 PM PDT by KYGrandma (The sun shines bright on my old Kentucky home......)
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To: KYGrandma


6 posted on 08/21/2011 1:58:02 PM PDT by ballplayer
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To: decimon
misfolded proteins in motor and cortical neurons

I wonder if Alzheimer's might be a disease similar to Mad Cow, in that people might be infected by eating the infected neural tissue of infected animals?

7 posted on 08/21/2011 2:00:16 PM PDT by Age of Reason
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To: decimon
researchers found ubiquilin2 isn't doing its job

So, how does one prevent this?

8 posted on 08/21/2011 2:09:23 PM PDT by bgill (just getting tagline ready for 6 months after you vote in Perry - Tried to warn you he's a RINO.)
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To: KYGrandma

I’m sorry to hear that.

My mother also died of this. It is truly horrible.

9 posted on 08/21/2011 3:09:15 PM PDT by justsaynomore (Herman Cain 2012 -
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To: KYGrandma

Prayers up for your friend. I also recently had a friend go through this.

I have become aware of some information that could be of interest to you and your friend.

Dr Mary Newport, whose husband was diagnosed with early Alzheimers, found a researcher at the NIH who has discovered that there is a problem with the breakdown of glucose metabolism mechanism in alzheimers. Apparently the medium chain triglycerides of organic coconut oil can give the brain and nervous tissue an alternative fuel. It literally can (at least in many who are responsive to it)halt the degeneration spiral. It is also my understanding that Dr. Oz made mention of this on a recent program, but I did not see it.

The good news is that the doc at NIH seems to indicate that Parkinsons, ALS, and other neurological-involved diseases can also be helped.

Follows is some information I prepared as a handout to a lecture I gave recently on the subject.


Dr. Mary Newport’s husband was diagnosed with Alzheimer’s. He was terribly frayed around the edges. He was quite unable to draw a clock face, which you may know, is one of the cognitive tests they give. She started researching what could be done. She ran across information on medium chain triglycerides (MCTs).

Apparently the brain has two mechanisms for feeding the brain cells. The first, of course, is the normal glucose metabolism. The other has to do with Ketone Bodies. Ketone bodies are the end product of the metabolism of MCTs.

There is developing a school of thought that Alzheimer’s is actually a Type III diabetes. Something has caused the usual insulin/glucose mechanism to go awry and the brain literally starves. If the person is given a source of MCTs, the brain can sustain the viability of the brain cells. They haven’t completely put their finger on what exactly is happening with the problems of the glucose metabolism mechanism, but the link between Alzheimer’s and diabetes and blood sugar issues is becoming unmistakeable.

Coconut oil is an excellent source of MCTs. Dr. Newport figured out that about 4 tbsp a day will provide enough of the ketone bodies to make a difference to the brain. She started feeding him coconut oil, and soon thereafter, his clock face drawings improved. She says to take it with food, and space the doses out; 2 tbsp in the morning, and 2 in the evening. It is a good idea to gradually increase the doses, because a large unaccustomed dose can cause an upset tummy. She suggests starting with a teaspoon with food once a day and go from there.

Based on her understanding of brain chemistry and the chemistry of the MCTs, (she is a pediatrician) Dr. Newport is pointing to the possibility that coconut oil could be helpful in other brain/nervous system disorders such as Parkinson’s,Lou Gherig’s (ALS), MS, muscular dystrophy, some forms of autism, macular degeneration, and others. Apparently, it is also helpful in smoothing out blood sugar issues in diabetics. Viruses, candida, and other fungal disorders can also be treated with coconut oil.

There are those (Bruce Fife, N.D., among them, ) who advocate coconut oil and flour for the treatment of weight control and gluten digestive disorder issues.

For a good summary/introductory article on this by Dr. Mary Newport, see “What if There Was a Cure for Alzheimer’s Disease and No One Knew?”

For a page of links to other articles on Dr. Newport’s web site, see this:

For use as a cooking oil:

For Bruce Fife’s website:

Dr. Newport states,”I have also heard from some people with diseases other than Alzheimer’s who believe they have seen some improvements, including other forms of dementia (FTD, CBD), Parkinson’s, ALS (Lou Gehrig’s), Huntington’s, MS, bipolar disease, even glaucoma and macular degeneration (which affect neurons).
That statement can be found on this document on her website:
By Mary Newport, M.D.

10 posted on 08/21/2011 8:29:42 PM PDT by TEXOKIE (Anarchy IS the strategy of the forces of darkness!)
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Coconut bump

11 posted on 08/22/2011 6:15:57 AM PDT by petercooper (2012 - Purge more RINO's.)
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Thanks for the info, but I am afraid it is much too late for my friend. He is completely paralized and cannot eat. We are probably talking days not weeks. I sure hope this info gets to those who need it.

12 posted on 08/22/2011 10:36:46 AM PDT by KYGrandma (The sun shines bright on my old Kentucky home......)
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To: KYGrandma

I’m so very sorry. I understand how that is. God bless.

13 posted on 08/22/2011 11:49:10 AM PDT by TEXOKIE (Anarchy IS the strategy of the forces of darkness!)
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To: decimon
Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia

The presser is too PC to mention that's X-linked.

14 posted on 08/22/2011 9:34:48 PM PDT by neverdem (Xin loi minh oi)
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To: decimon

Thanks for posting this.
I wanted to let you know I have forwarded the information to medical people in Canada who work with ALS patients that are very excited to get this information. They have had to write up an information sheet because they have received so many requests asking about this information from patient families.
Concerning ALS-related press releases of 21-22 August 2011
On 21 August 2011, the journal Nature posted the online publication of the following paper:
Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia
Han-Xiang Deng, Wenjie Chen, Seong-Tshool Hong, Kym M. Boycott, George H. Gorrie, Nailah Siddique, Yi Yang, Faisal Fecto, Yong Shi, Hong Zhai, Hujun Jiang, Makito Hirano, Evadnie Rampersaud, Gerard H. Jansen, Sandra Donkervoort, Eileen H. Bigio, Benjamin R. Brooks, Kaouther Ajroud, Robert L. Sufit, Jonathan L. Haines, Enrico Mugnaini, Margaret A. Pericak-Vance & Teepu Siddique
The authors represent five academic institutions, with the lead investigators based at Northwestern University in Chicago.
Synopsis: The underlying causes of most forms of ALS have not been identified. This new study has confirmed a mechanism common to all forms of ALS, reinforcing the need to continue developing therapies related to that mechanism. The problem is a breakdown in the recycling system for damaged proteins in specific neurons in the spinal cord and brain that results in severely damaged cells. Problems with this mechanism also likely play a role in other neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease.
This study is a validation of much research currently being conducted in Canada. It is a new piece of the puzzle that will help us find a treatment/cure for ALS. Why is the study of interest?
One, it confirms that pathways and mechanisms we have been focusing on as a research community for the past 15 years are important since the protein (ubiquilin2) which they report in this paper (part of the natural intracellular mechanisms for processing & degrading) has mutations in human ALS patients. However, it is important to note that this study does not identify any brand new mechanisms or pathway.
Two, the results in human patients validate the cellular and animal experimental models of ALS which have been used for the past 15 years, as those models already led to the study of this particular intracellular mechanism. In addition, the person who led the way into this line of study was ALS Society of Canada board member and Research Committee chair Heather Durham, PhD (Montreal Neurological Institute) who began studies of the proteasome and of chaperone molecule functions in the late 1990s.
Three, it should be noted that the presence of neuronal protein accumulations/aggregates/inclusions in a number of adult-onset neurodegenerative disorders — such as Alzheimer’s and Parkinson’s as well as ALS — has already been the impetus behind the development of treatments to counteract the formation of such inclusions. This new study provides additional motivation to pursue preclinical studies and clinical trials to develop and test such therapies.
In summary
A solid and interesting new finding. Hopefully it will attract additional basic scientists to study these mechanisms in ALS, and garner support to develop and test new therapies related to those mechanisms.
Scientific Explanation
There has been considerable publicity surrounding this study with coverage by major news sources.
The authors identify mutations in the gene “UBQLN2”, which codes for the ubiquilin 2 protein, in a large family with ALS (FALS). Additional mutations in the same gene were found in four other unrelated FALS families. It is of interest that dementia was a feature of a number of UBQLN2-linked patients. Ubiquilin2 is one protein component of a complex system found in all cells which repairs or disposes of proteins as they become damaged. When this protein processing system is unable to remove or repair damaged proteins, the damaged proteins begin to accumulate in the cells. Study of postmortem spinal cord and brain samples from affected UBQLN2-family members, and postmortem spinal cord samples from a number of other ALS patients (including both familial and non-familial) demonstrated the accumulation of UBQLN2 in “skein-like inclusions” in all cases examined.
There is a significant body of published work by a number of investigators in the field which has established that proteins which have been implicated in the pathogenesis of ALS as a result of mutations found in FALS (ie., SOD-1, TDP-43, FUS, and optineurin) clump together inside of motor neurons, forming aggregates or inclusions. The formation of clumped or aggregated proteins in specific subsets of nerve cells has long been identified as a hallmark of other neurodegenerative disorders including Huntington’s, Parkinson’s and Alzheimer’s. Thus, interest in how these aggregates/inclusions arise and how nerve cells normally prevent the process led to investigation of intracellular protein processing and degradation. In the ALS field, studies using cellular and animal models to understand why naturally programmed mechanisms to degrade problem proteins do not work in motor neurons began in the late 1990s. These natural mechanisms are complex and involve a number of protein components which work in several locations inside the cell, and communicate with each other by systems that escort damaged or mutant proteins to the appropriate location. The newly identified FALS protein, UBQLN2, is one of the components of this complex mechanism.
This new publication confirms that this well established and significant area of basic science research does have direct relevance to ALS, as mutations in the UBQLN2 protein found in the five FALS families lead to impairment of the protein degrading mechanisms. Further, the study reinforces the validity of the cellular and animal models being used to identify important mechanistic pathways of direct relevance to ALS.
Finally, while confirmation of disruption of intracellular protein processing as a common pathway in ALS is important, it is also important to put the results in context. The results do not explain fully what happens “upstream” which leads to these problems in most cases of ALS. Although there are still further questions to be answered, it is encouraging to know that researchers are indeed on the right track.

15 posted on 08/24/2011 8:35:21 PM PDT by Freeper Fanatic
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To: Freeper Fanatic
Thanks for posting this.

You're welcome.

I wanted to let you know I have forwarded the information to medical people in Canada who work with ALS patients that are very excited to get this information.

I guess that no one can keep on top of things.

16 posted on 08/24/2011 8:41:46 PM PDT by decimon
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To: decimon

It’s very true. So many pieces of the puzzle are published but never connect with the right people who can actually use it to assemble the information and form it into the big picture.

17 posted on 08/24/2011 9:25:34 PM PDT by Freeper Fanatic
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