Improving Oxygen Supply to the Spinal Cord May Help Prevent ALS Progression, Mouse Study Suggests

Improving Oxygen Supply to the Spinal Cord May Help Prevent ALS Progression, Mouse Study Suggests

Increasing blood flow in the spinal cord by injecting a long-acting vasodilator can help prevent the progression of amyotrophic lateral sclerosis (ALS) in mice, a study shows.

The study, “Single injection of sustained-release prostacyclin analog ONO-1301-MS ameliorates hypoxic toxicity in the murine model of amyotrophic lateral sclerosis,” was published at the journal Scientific Reports.

Hypoxia (low oxygen level) has been found to contribute to the development and progression of several human diseases, including cancer and neurodegenerative disorders.

Studies have shown that in both ALS patients and mice with the disease, hypoxia signals are increased compared to healthy controls. Moreover, the blood-spinal cord barrier, which is composed of blood vessels and controls oxygen and nutrient supplies to the central nervous system, often is damaged in ALS.

These findings suggest that impaired oxygen supply to motor nerve cells of the spinal cord may have a role in ALS progression.

Researchers from Osaka University in Japan evaluated levels of the well-known biomarker of hypoxia, HIF-1alpha, in the spinal cord of ALS patients and genetically engineered mice carrying the mutated SOD1 gene, which is linked to familial ALS.

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In accordance with previous data, the team found that in spinal cord samples taken from both patients and mice, the levels of HIF-1alpha were increased significantly compared to healthy controls. This finding further suggests that nerves cells in the spinal cord of ALS patients are in an environment with low oxygen levels.

Based on these results, researchers decided to explore the potential of an experimental vasodilator compound, ONO-1301-MS, to reverse this hypoxic effect.

ONO-1301 is a synthetic prostacyclin agonist that was designed to have a strong and longer-lasting blood vessel dilation effect compared to other similar available compounds. In previous studies, it decreased vascular tone and increased blood flow, improving the neurological function in rats with cerebral infarction (brain tissue dying due to lack of oxygen).

The team administrated a single subcutaneous (under-the-skin) injection of ONO-1301-MS, a sustained-release form of ONO-1301, in mice with mutated SOD1. These mice showed significantly improved motor function and increased body weight compared to placebo-treated mice.

Further analysis of mice’s spinal cord showed that those treated with ONO-1301-MS had significantly more live motor nerve cells. However, the treatment had no effect on inflammatory markers or mice survival rate, most likely due to ONO-1301-MS’ inability to fully alleviate the hypoxic stress induced by ALS.

A new analysis of HIF-1alpha levels confirmed that treatment with ONO-1301-MS reduced hypoxia in the spinal cord of mice with ALS.

Moreover, it could increase by approximately 2.5-fold the levels of brain-derived neurotrophic factor (BDNF), which is an important mediator of nerve cells’ survival, compared to placebo.

The team also found that the levels of mitochondria ATP (the energy source of cells) in the spinal cord of mice were partially restored upon treatment with ONO-1301-MS. This suggests that the treatment improved ATP production and blood supply in the spinal cord of mice with ALS.

Supported by these results, the team concluded that “increasing blood flow in hypoxic regions of the spinal cord might play an important role in protecting against neurodegeneration.”

Additional studies are warranted to clarify the potential role of hypoxia in ALS. Still, “a treatment modality that inhibits hypoxia holds great therapeutic promise for treating ALS patients,” they wrote.

5 comments

  1. Hi all of you with ALS. There is a simple treatment that does something like the drug mentioned in this article and that is EWOT.
    Exercise with Oxygen Therapy. Simple, you need a source of oxygen like an H cylinder or a top end oxygen compressor either of which needs to deliver 10 liters of oxygen a minute. Once you get that then you just need to put your oxygen mask on your face and start to exercise as much as you can for 1-15 minutes every 4 to 8 hours. For those who are too gone for exercise then you can do the same thing with functional electrical stimulation. These are inexpensive muscle stimulators that come with pads that are attached to your muscles. Your primary caretaker should be able to put these on and to turn on the machine to the level you can stand. This will increase your oxygen to the spinal cord and to your muscles and you should be doing better within a day or two! Good luck! For more info on ALS go to youtube and put my name steenblock and the letters ALS in to get some more info. This though is old info and there is lots more now known since then. One of the things is the loss of pericytes in the spinal cord blood vessels and the dysfunction of these is what is causing this lack of oxygen. They would appear to be replaceable by a special kind of stem cell and I am in the process of testing this stem cell to see if it is the true answer (along with removing all the bad things that are causing ALS- like endotoxins, CD8 T-lymphoctyes, monocytes, nanoparticles, Lyme, H.pylori, etc.)

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