Compound Called MITO-PIP May Have Potential as Gene Therapy for Mitochondrial Diseases

Compound Called MITO-PIP May Have Potential as Gene Therapy for Mitochondrial Diseases

A compound that can silence a gene in a very specific manner was adapted by researchers to be used inside mitochondria — opening the possibility of manipulating genes linked to mitochondrial diseases.

MITO-PIP, as the scientists call the compound, binds to a stretch of mitochondrial DNA that is involved in several disorders, including Leber’s hereditary optic neuropathy and mitochondrial myopathy.

While their study “Creation of a Synthetic Ligand for Mitochondrial DNA Sequence Recognition and Promoter-Specific Transcription Suppression,” published in the Journal of the American Chemical Society, provided a proof-of-concept that it is possible to manipulate mitochondrial genes in this way, the researchers are intent on continuing to refine the compound.

They are now aiming to improve MITO-PIP so that it only enters mitochondria that are faulty, leaving the healthy ones to do their work, Ganesh Pandian Namasivayam, who led the research team with Kyoto University in Japan, said in a press release.

PIPs (Pyrrole-imidazole polyamides) have been used to target disease-causing genes in normal cell DNA. They act by binding to their target stretch to prevent so-called transcription factors from initiating the process of making a protein from a gene.

Transcription factors are molecules that control gene activity by directly interacting with DNA and the protein-making machinery.

But PIPs lacked the ability to penetrate the membranes surrounding mitochondria. To solve this, the team linked a PIP to a protein fragment that possessed the specific ability to cross mitochondrial membranes.

The team developed a MITO-PIP that bound to a DNA stretch normally occupied by a factor called TFAM. TFAM controls genes crucial for energy production. One of them is ND6 — a gene that contributes to Leber’s, a disease marked by vision loss, and mitochondrial myopathy, in which patients develop muscle weakness, seizures, and learning difficulties.

First, the researchers conducted experiments to make sure that MITO-PIP really ended up inside the mitochondria. Using a fluorescent dye, they traced the factor, and confirmed that it was, indeed, inside mitochondria, with no evidence of it in the cells’ nuclei.

Further experiments confirmed that the compound lowered the amount of ND6 by 60% to 90%, depending on the dose the team used.

“Our proof-of-concept study provides a fresh platform that opens new avenues for DNA-based functional ligands that are capable of altering the mitochondrial genome in a sequence-specific manner,” said Hiroshi Sugiyama, the study’s senior author.

The study was performed in lab-grown cells, and human tests are not even in the planning stage. Nevertheless, the findings show that the treatment has the potential to benefit people with a variety of mitochondrial diseases.

Next, “we plan to develop an advanced version of MITO-PIPs that can identify and localize only inside diseased mitochondria,” Ganesh said.


  1. deborah hollen says:

    please call or email me.. I had a biopsy and geno syquencing deletion assay test.. and have whorled blue mito fibers..they said they don’t know what it is.. or why.. but my body is stiff all over.. my mom and son’s too.. as I believe its a maternal mito condition.. please help me..I just have Obama care and they are limited on the testing that is required.. call me 619 888 0132

    • Magdalena Kegel says:

      Dear Deborah,
      I am truly sorry to hear out yours and your family’s condition.

      We at Mitochondrial Disease News did not perform the research described in the article. We merely report on research and drug development advances within the field.

      The study was performed by a group of researchers in Japan. But unfortunately, the research is in its very earliest stage and is nowhere near being tested in humans.

      The only thing that I can advise you is to search for a clinical trial to attend. We frequently include information about clinical trials in our new newsletter.

      I am sorry I am not able to be of more help. I sincerely hope you find the help you need.

    • Shasha says:

      HI, This is what helps my mitochondria
      and more. Carnitine/acetylcarnitine/coenzyme Q10/detoxing heavy metals by Far Infrared Sauna/Mg/Zn/fish oil/evening primrose oil/lecithin/low sugar/Cr/alpha lipoic acid/VitC/Vit E/coenzymated B vitamins and more help me, but still not enough. PQQ may help make more mitochondria and exercise. Some people use D ribose. Carnosine/Benofotiamine(fat soluble Vit B1)/Vit A/Fe/Mn/luteolin/NADH/Krill oil/phosphaditylserine/DMAE help me. I have not tried the R version of alpha lipoic acid yet. No gluten/dairy/soy/sugar/GMO/food with a label/heated oils/saturated/monounsaturated fat…taking vitamins/minerals/good oils/strong probiotic/LDN (helps block hidden gluten)…detoxing helps me.

  2. Shasha says:

    If they get rid of the bad mitochondria and all mitochondria are hurt then no mitochondria would be left? I would like to know how to heal the DNA in the mitochondria. Antibiotics/heavy metals/antifreeze in poison ivy cream hurt my mitochondria and I was born with hurt mitochondria from my mom.

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