Gene Therapy to Strengthen Nerve-Muscle Connection Prevents ALS Progression in Mice

Gene Therapy to Strengthen Nerve-Muscle Connection Prevents ALS Progression in Mice

A gene therapy aimed at strengthening the connection between motor neurons and muscle prevented nerve degeneration and increased the life span of mice with amyotrophic lateral sclerosis (ALS), a study showed.

Since researchers believe that neurodegeneration in ALS starts at the junction between nerves and muscle, the findings suggest that preventing the connection from breaking down could be a good way to stop the disease from progressing.

The study, “DOK7 gene therapy enhances motor activity and life span in ALS model mice,” was published in the journal EMBO Molecular Medicine.

Interestingly, the University of Tokyo researchers did not develop the gene therapy with ALS in mind. They were trying to prevent a disease called DOK7 myasthenia that is caused by mutations of the DOK7 gene.

The gene encodes a protein that is a key component of the neuromuscular junction. Without it, the connection does not form properly, and patients with DOK7 myasthenia develop severe muscle weakness.

When the team used gene therapy to try to restore DOK7 expression, they discovered that it not only prevented deterioration of the nerve-muscle connection, but it also improved movement and increased survival in mouse models with the muscle condition. The researchers saw the same thing in a type of muscular dystrophy.

Since scientists believe that the neuromuscular junction is the starting point for the nerve deterioration in ALS, the Tokyo researchers decided to try DOK7 gene therapy to treat ALS.

Using it in an ALS mouse model prevented degeneration of the nerve-muscle connection, as in the earlier experiments. This, in turn, prevented muscles from breaking down, while having no effect on the number of spinal motor neurons.

The therapy not only strengthened the mice’s neuromuscular junctions but also increased their life span, the team said.

DOK7 is a protein found on the muscle side of the neuromuscular junction. It activates a protein called MuSK, or muscle-specific kinase, which the body needs to maintain nerve-muscle connections.

Earlier studies in animal models of ALS suggested that loss of the nerve-muscle connection occurs independently from the death of motor neurons. That prompted the Tokyo research team to argue that gene therapies targeting the neuromuscular junction in ALS might be even more effective when used in combination with treatments capable of boosting motor-neuron survival.

13 comments

    • Magdalena Kegel says:

      Hi Karen,

      It is difficult to say something about the timeline for us at ALS News Today. Researchers need to perform plenty of studies to show the safety of a treatment in animals before advancing to human trials, and the speed depends on the resources—human and financial—of the research team.

  1. Charlie says:

    For such an interesting and promising treatment method funding may be quickly forthcoming. We could look for Phase 3 Clinical Trials being completed in about 5 years time so this is quite a fast progression.

  2. larry marshall says:

    my wife has ALS, i wish they would give people access to experimental drugs, they have nothing to loose!

    • Tim Bossie says:

      Hi Larry, we are sorry to hear about your wife. ALS is a terribly devastating disease on everyone in the family. When a drug gets through its initial research and study, then they will take into a clinical trial. This is where the human tests begin in a controlled environment.

  3. Kenneth C. Lewis, MD says:

    As a physician and a scientist I understand the need for controlled trials. However, with this devastating disease, compassionate use should be made available to those not involved in trials. They would have to accept the unproven experimental stage of the treatment and possible adverse side effects to be allowed to use these treatments before trials are concluded. Most ALS patients no that the “side effect” of no treatment is imminent death. ANY possible side effect pales in comparison to the known effect outcome. Coherent patients should be given this option quicker and with less hassle. I am a little suspicious of drug companies who may have some incentive to “control” documentation of side effects to increase marketability of the drug when finally approved and ready to produce profit. of course profit drives research and the availability of new treatments, but OUR tax dollars have facilitated much of that research and WE should be allowed to “take a chance” in a setting where not doing so has a pretty bad “side effect”. Americans frequently have to travel outside this country to get access to cutting edge treatments. Is the FDA working for the patients best outcome or the drug companies “best case marketability” outcome.

    • jason says:

      Totally agree, I know my brother would be willing to take in experimental trials if only he had an option to do so.

      It is a pandora’s box situation however, what about all the other terminal illnesses that people have, they would want the same…

      Ultimately, I think easier access to those with terminal illnesses to experimental treatment would be much welcomed.

  4. Karen says:

    Agreed I am desperate and all I get is the run around. It takes forever to even get into a pulmonary doctor or a neurologist for diagnosis.

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