Status
Not open for further replies.

stu2742

New member
Joined
Apr 23, 2009
Messages
9
Reason
Learn about ALS
Country
uk
State
london
City
london
There seems to be a lot of encouraging news about research at the moment..here's another article I came across this morning....cheers stu

Science News Share Blog Cite Print Email BookmarkCompound Shows Potential For Slowing Progression Of Lou Gehrig's Disease

ScienceDaily (Oct. 20, 2009) — A chemical cousin of a drug currently used to treat sepsis dramatically slows the progression of amyotrophic lateral sclerosis, better known as ALS or Lou Gehrig's disease, in mice. The results offer a bit of good news in efforts to develop a therapy to stop or slow the progression of a disease that generally kills its victims within just a few years.
Science News Share Blog Cite Print Email BookmarkCompound Shows Potential For Slowing Progression Of Lou Gehrig's Disease
ScienceDaily (Oct. 20, 2009) — A chemical cousin of a drug currently used to treat sepsis dramatically slows the progression of amyotrophic lateral sclerosis, better known as ALS or Lou Gehrig's disease, in mice. The results offer a bit of good news in efforts to develop a therapy to stop or slow the progression of a disease that generally kills its victims within just a few years.

In a paper published online Oct. 19 in the Journal of Clinical Investigation, scientists studied the use of a form of an enzyme known as activated protein C, or APC, to slow the cell death that occurs in ALS. They were able to extend the lifespan of mice with an aggressive form of the disease significantly, by about 25 percent. The compound also extended the length of time that the mice were able to function well despite showing some symptoms of the disease, and it reduced the pace of muscle wasting that is a hallmark of ALS.

While the investigators say that more research must be done before the enzyme is tested in people with the disease, they are encouraged that the work involves a compound that has already been proven to be safe and is currently given to patients via a common injection for another condition. The team hopes to test a treatment in patients within five years.

The work was done by investigators from the University of Rochester Medical Center, the University of California, San Diego School of Medicine, The Scripps Research Institute in La Jolla, University of Notre Dame, and a Rochester-based start-up biotech company, Socratech.

Corresponding author of the study is neuroscientist Berislav Zlokovic, M.D., Ph.D., of the University of Rochester Medical Center, whose group collaborated with laboratories led by Don Cleveland, Ph.D., a widely recognized ALS expert at UC San Diego, and John Griffin, Ph.D., an APC expert at Scripps. First authors of the paper were Instructor Zhihui Zhong of Rochester and post-doctoral associate Hristelina Ilieva of UC San Diego.

The research involved mice with a mutation in a gene known as superoxide dismutase 1 (SOD1), which plays an important role keeping cells safe from damaging molecules known as free radicals. While the cause of most cases of ALS is unknown, scientists do know that SOD1 plays a role in approximately 3 or 4 percent of cases – providing an opportunity to study the disease's initial steps, which occur long before key nerve cells appear sick or die. In addition, recent studies have suggested that the accumulation of mutant forms of SOD1 is linked to most sporadic cases of ALS.

Cell death is central to the symptoms of ALS, a chronic disorder of motor neurons in the brain, brainstem and spinal cord which results in a progressive paralysis that generally kills individuals within five years of onset. Currently there is no cure or even a treatment that can effectively slow disease progression.

In a surprising finding last year, a team led by Zlokovic and Cleveland found that SOD1 mutations weaken the crucial natural barrier between blood and the spinal cord. In effect, blood vessels in the spinal cord become leaky, allowing toxic substances to flood into the spinal cord. Because of the defect, motor neurons are exposed directly to biochemical byproducts of hemoglobin such as iron, which forms reactive oxygen molecules that injure or kill neurons.

Now, the team has shown that APC dramatically lessens the activity of the SOD1 mutation. This protects neurons that are under assault by blocking the synthesis of aberrant forms of the molecule in motor neurons and other cells in the spinal
cord. These include microglia cells, which the Cleveland laboratory has shown play a key role in the inflammatory response and progression of ALS. In addition to reduced SOD1 activity, the flow of dangerous byproducts of hemoglobin into the spinal cord was eliminated by APC, saving neurons.

Currently the group is studying alternate forms of APC, in an effort to create the form that best quells the symptoms of ALS while causing few unwanted side effects, such as bleeding. Zlokovic says the form of APC currently used to treat sepsis carries an increased risk of bleeding and likely will not be appropriate for treating ALS in humans.

While other researchers are exploring the possibility of silencing SOD1 to treat ALS, Zlokovic notes that most approaches would require invasive surgery and delivery by direct infusion into the spinal cord. APC, in contrast, is already approved as an injection.

"The success of this research project has been very gratifying, and we are hopeful that a form of APC will ultimately be useful as a treatment for this disease," said Zlokovic, who is professor of Neurosurgery and Neurology and director of the Center for Neurodegenerative and Vascular Brain Disorders at Rochester.

"I began this line of research at the request of an old friend – a childhood pal with whom I was friends my whole life, until he got ALS and died just a few years later. It was very sad. Clearly, something has to be done – new treatments are needed," added Zlokovic.

Zlokovic and Griffin are named as inventors on several patents and applications related to APC, and Zlokovic is the founder of ZZ Biotech, a company developing new treatments for stroke and Alzheimer's disease. Zlokovic and the University both hold a stake in ZZ Biotech and Socratech.

Other authors include Lee Hallagan, Robert Bell, Itender Singh, Nicole Paquette, Meenakshisundaram Thiyagarajan, Rashid Deane, Steven Lane, Anna Zlokovic, Todd Liu and Konstantin Stojanovic of the University of Rochester; Jose Fernandez of Scripps; Nienwen Chow of Socratech; and Francis Castellino of Notre Dame. The work was funded in part by the National Institutes of Health.
 
Good news indeed. Thank you Stu.We need a hurry up break through to stop this disease.We are fortunate to have dedicated people working hard to find us help.Yahoo
 
That is very interesting about the blood vessels leaking into the spinal cord with ALS. That is not something you hear much about. I wonder if it applies to sporadic (non familial) ALS as well. I have continued to take fish oil because I always took it before and it's supposed to be good for you, but they say it thins your blood and now I wonder if it would make this leakage problem worse.
 
Its really too bad they wont let people be the "mice" I know my husband would have done anything to be in a undetermined trial as well as most ALS patients. Really, how bad would the outcome be?
 
  • Like
Reactions: Hal
I'm still wrestling with the whole placebo thing in clinical trials. Correct me if I'm wrong here, but the placebo is the fake drug given to participants that don't know they're getting it. Oh, I know they are aware that the chance exists but for all they know, they could be getting the actual drug.

It is obvious to me that the placebo is meant to not work. I'd hate to spend my time taking something to help that is designed to be ineffective. I just don't get it.

In my mind, enlist 100 people (or however many) in the trial and give them all the drug in design. If it doesn't work on any of them, its a flop. If it works on all of them, jump for joy! If it works on half of them, maybe the dosage could be adjusted to make it more effective.

Placebos (as you can tell) bother me.

Zaphoon - just some thoughts...
 
They both me too! They claim they are needed to monitor difference in progression between the ones that get the real thing. As if there aren't enough of us around they could gauge against. Stupid! Now you know how I feel about them too. LOL.
 
i agree as there is no cure or stopping progression (3 months ) anyone who gets better it is surely not in their mind
 
I agree in cases where they use objective tests like FVC or total survival time. But sometimes they use the ALSFRS or similar ratings, and these tend to be subjective. How much trouble are you having using silverware, or walking, or swallowing. It is easy to shade the score one way or the other depending on how optimistically you view your symptoms. I've read many stories of people having stem cell or other questionable treatments and they say they feel stronger, they feel better, at least for a while. But their survival isn't actually any better in the end. Did they really get stronger, or were they just more optimistic? If they're walking more than before, is it because they are truly stronger, or maybe just working harder?

There can be real placebo effects even with a disease like ALS, especially because there don't seem to be good objective measurements of progression. I think that is one area of research, looking for "biomarkers" so they could take a blood sample and measure how fast your nerve cells are dying. This would help with drug evaluation and probably allow for more reliable testing in smaller groups. But there doesn't seem to be any such measure now. Probably FVC is best but that only measures one part of the body.
 
Status
Not open for further replies.
Back
Top