Increasing Dok-7 Protein Levels May Improve ALS Patients’ Muscle Function, Study Reports

Increasing Dok-7 Protein Levels May Improve ALS Patients’ Muscle Function, Study Reports

Increasing the production of the muscle protein Dok-7 may be a way to treat the muscle weakness in ALS, a Japanese study reports.

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

A hallmark of amyotrophic lateral sclerosis is loss of neuromuscular junctions, or connections between neurons — or nerve cells — and muscles. This communication is crucial for muscular activity, including walking, jumping, eating, and breathing.

Previous research has shown that Dok-7 is an essential player in the formation of neuromuscular junctions. It has also shown that mutations of the gene that produces the protein lead to DOK7 myasthenia, a disease that affects neuromuscular joint structure.

Yuji Yamanashi’s team demonstrated that increasing the production of the human version of DOK7 stopped the degeneration of motor nerve terminals and slowed muscle atrophy in mice with ALS.

“Our data indicate that DOK7 gene therapy suppressed NMJ [neuromuscular junction] defects and muscle atrophy in ALS mice” at 30 days after treatment, the researchers wrote.

Importantly, the gene therapy not only improved the mice’s ALS symptoms, but also lengthened their lives. Mice that had the therapy lived around 166 days, versus 154 in the untreated mice.

“This therapy also prolonged duration of survival after ALS onset” to about 64 days, compared with 50 for the untreated mice.

Together, the results support the notion of developing DOK7 gene therapies to treat movement neuron loss and muscle weakness associated with ALS.

“This study originates from a finding in basic, biological research, which had no particular disorder as a target,” Yamanashi said in a news release. A number of collaborators in basic and medical research took part in the effort, which was supported with multiple public grants, he said.

“Acknowledging the huge contributions of our collaborators and supporters, we would like to do our best to understand the causes of ALS and other intractable disorders, with the aim of developing effective therapies,” he said.


    • Andrik says:

      It should be mentioned that they used an viral vector to deliver the DOK7 gene to ALS model mice. It is a very preliminary study and requires further stringent tests before we can say its safe for human trials.

  1. Robert says:

    How was the Dok-7 protien increased? Was it oral or some other means. If oral, what was given to the mice? What were side effects? This process appears to increase life span about 10%.

    • Andrik says:

      It was increased through the introduction of a DOK7 transgene through a viral vector. In simpler terms, using a virus to deliver it specifically to muscle cells, they added extra DNA coding for the Dok-7 protein. It’s very likely they just injected the mice with the virus juice.

  2. Dr. D. N. Yadav says:

    It seems stem cell therapy is in clinical testing stage for ALS. How much more time will be needed and finally approved by US FDA? Can anyone suggest on this? What about gene therapy. Pl. pass comments. I have taken Radicava injection for 10 months but no improvemet in my illness.

  3. Aaron Knobloch says:

    This sounds like the Dok-7 is a naturally occurring protein, either produced by the human body or somehow acquired by diet or possibly exposure during some other means, inhalation or contact. If this is true, then there may be some nutrient that spur the body’s manufacture of Dok-7? Pharma probably won’t help. Any naturopaths care to weigh in?

    • Andrik says:

      I feel as if you are oversimplifying the problem… to answer your questions:
      1. Yes Dok-7, like any protein your body produces, is naturally occurring.
      2. You generally don’t acquire a protein by just eating/inhaling/contacting it. You eat a protein, your body breaks it down into amino acids, which your cells use to build your own proteins.
      3. So how do you spur the body’s manufacture of Dok-7? That’s the very question this research group is addressing.

      No naturopath can put together a bunch of ‘natural ingredients’ to get your cells to produce a specific protein. So this research group tried to force the cells to express the protein using gene therapy.

      By the way the reasoning for this gene therapy is:
      1. ALS patients have decreased NMJs (neuromuscular junction) (where your nerves connect to the muscle, you can imagine in ALS the nerves to the muscle don’t work so well and such)
      2. NMJ is formed by another protein called
      MuSK (muscle-specific receptor tyrosine kinase)
      3. Dok-7 is another protein that is required for activating MuSK.
      4. If we somehow can get the body to produce Dok-7, we might be able to treat ALS. Thus we use gene therapy to add some DOK7 genes!

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