New study suggests gout drug, colchcine, may help treat Myotonic Dystrophy DM1 in future

A new study by several major researchers in the myotonic dystrophy field had a very interesting study that identified a FDA approved drug that may help with myotonic dystrophy.  However, as usual, more research is needed to validate the approach. The study identified and validated a cell based assay screening tool that enabled the researchers to look at a number of drugs. The most promising drugs were colchicine, thiocolchcine,suprafenacine, amsacrine, azathioprine, The researchers decided to concentrate on was Colchicine an already approved FDA drug for gout and familial Mediterranean fever (FMF), 

We primarily focused on colchicine because it is an inexpensive, FDA-approved, natural therapeutic that is generally well tolerated and is currently used in the clinic to treat gout and familial mediterranean fever (FMF)“‘

The next step the researchers took was to use colchicine in mice that had been altered to have myotonic dystrophy. The drug was injected into these mice. The researchers found that the amount of mutant RNA was decreased in  the muscle cells.

“Collectively, these data demonstrate that microtuble inhibition in vivo leads to a selective reduction in expanded CUG RNA levels without broadly affecting the transcriptome”

Next the researchers tested colchicine in patient cells with myotonic dystrophy. They selected patients cells with a repeat count of 1900-3000 repeats. The results were positive

“we observed significant rescue of missplicing”


The researchers established a cell line that enabled them to screen a large number of compounds that might help to reduce DM1 in theory. They found a list of candidates and then selected colchicine as a drug to model

“We then validated the use of a microtubule inhibitor in the HSA DM1 mouse model and in DM1 patient cells with colchicine an FDA approve natural microtubule inhibitor currently used in the clinic. Our results provide proof of principle for the identification of compounds and cellular targets selectively modulater r(CUG)exp levels in DM1 using cell-based screening.

Our Observation of a partial rescue in DM1 relevant missplicing in multiple models warrants further evaluation of colchicine. The study is NOT sufficient to address the therapeutic efficacy of colchicine or of general microtuble inhibition in the treatment of DM1, It is important to determine if there is a positive trade off between the therapeutic efficacy in reducing DM1 symptoms in  relation to known toxicity from microtuble inhibition. As an example, and although very rare, myopathy has been reported in some individuals with compromised renal function who had been treated chronically with colchicine for gout. Future Long term treatment in DM1 animal models such as HSA at clinical doses to evaluate the reversal of DM1 phenotypes are a [prerequisite to determine if any clinical studies are warranted”

Overall this is a promising approach that needs more study. However, for those in the end stages of Myotonic dytrophy disease this may be something to discuss with your medical staff.




NOTE:  Transcriptome definition – Wikipedia

The transcriptome can be seen as a subset of the proteome, that is, the entire set of proteins expressed by a genome.. However, the analysis of relative mRNA expression levels can be complicated by the fact that relatively small changes in mRNA expression can produce large changes in the total amount of the corresponding protein present in the cell.




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New Drug Approach Validated

This info is from 2018 but still very valid for today….. From Med Express

Researchers complete myotonic dystrophy treatment research

Translational Genomics group. Credit: Asociación RUVID

Researchers at the Translational Genomics laboratory of Valencia University and the INCLIVA health research institute have just discovered a new approach for the treatment of myotonic dystrophy, a rare and incurable neuromuscular disease which does not have specific treatment. Their work has been published in Nature Communications.

Their research has discovered molecules that are able to increase the expression of MBNL proteins, which are crucial for the , and that way prevent many of the alterations present in the murine and cellular models of the disease.

The uncovered molecules are known as antagomiRs. An antagomiR is a small oligonucleotide which has been noticeably modified to improve its pharmaceutical characteristics. It is added to specific regulatory RNA, in this case miR-23b and miR-218, which naturally suppress the expression of MBNL proteins. By degrading the suppressors, they increase endogenous expression, which is a therapeutic target for the disease. Oligonucleotides are a new type of innovative medicines which, according to Beatriz Llamusi, co-author of the project, “are quickly reaching clinical practice and could provide medium-term solutions for numerous diseases which are intractable today.”

Myotonic dystrophy originates due to expansions of the CTG triplet of the DMPK gene which, through a well documented process, abduct MBNL proteins and prevent them from carrying out their normal functions within the cell. Estefanía Cerro Herreros, first signer of the article, graphically describes this process: “It is as if we gathered all our teachers in a park instead of in a classroom: we would paralyse education.” She adds that “the treatment we have discovered consists of increasing the endogenous expression of said genes. As if, following the previous example, we hired more teachers.”

A crucial aspect of the research is the team’s interest on collaborating with the pharmaceutical industry to transform these discoveries into real medicine. Rubén Artero, head of the research, believes it is necessary to create an environment around research centres “which favours the continuity of scientific discoveries until they develop into solutions that are requested by society.” In this sense, the Translational Genomics group of Valencia University has previous experience with public-private collaborations focused on these developments and, in this specific case, is negotiating the creation of a spin-off company to progress in the development of these composites as potential therapies for . The research team recently organised the first Spanish convention on the use of oligonucleotides in human therapies (SMOT1) with broad participation of companies in the sector.

New Drug Combo Study Helps Push back Myotonic Dystrophy in Mice

A recently published article used a combination of erythromycin and the prodrug of furamidine (pafuramidine) orally administed to mice that had Myotonic Dystrophy. This combination help with the problems that DM causes in the cells. A promising potential therapy however with some limitations.

Already a study back in 2014 showed that Erythromycin an FDA approved drug can help with a therapeutic approach to the disease in Mice. Many individuals have also taken this FDA approved drug to help with the myotonic dystrophy disease.

The new combination involves combination of erythromycin and the prodrug of furamidine (pafuramidine), The second drug pafuramidine is not available yet. It was studied in a phase III study for African sleeping sickness but not easily commercially available. The drug was found effective for African Sleeping sickenss. It looked very promising with a phase 3 study in many countries in Africa.  However, the phase I testing in healthy volunteers there was a possible adverse reaction to pafuramidine casing renal issues in 2 of 175 healthy volunteers (1.1%) . Looking more deeply into the adverse reaction there were 2 individuals with serious reactions including one that required dialysis as a probably result of the drug pafuramidine.  As such the drug was not further pursed. In the study in Mice with myotonic dystrophy the amount of pafuramidine was 5X lower than what was used in humans for African sleeping sickness so potentially much safer. There is some research into other analogs (Variations) of pafuramidine for future studies.

Th study still shows that erythromycin can be potentiated (enhanced) by other drugs but this combo seems to dangerous to use in humans due to the kidney reactions in a small group. Its small but the drug seemed to seriously degrade the urinary system

Here is some information on the study:

In DM1 patient-derived myotubes, the rescue of mis-splicing was observed with little to no celltoxicity. In a DM1 mouse model, a combination of erythromycin and the prodrug of furamidine (pafuramidine), administered orally, displayed both additive and synergistic mis-splicing rescue. Gene expression was only modestly affected, and over 40% of
the genes showing significant expression changes were rescued back toward WT expression levels. Further, the combination treatment partially rescued the myotonia phenotype in the DM1 mouse. This combination treatment showed a high degree of
mis-splicing rescue coupled with low off-target gene expression changes. These results indicate that combination therapies are a promising therapeutic approach for DM1. But the exact Drug pafuraminde has a severe adverse reaction so it can not be used now. Perhaps other drugs that potentiate erythromycin can be used in the future.



Below is the supporting information including the instructions for making the second drug pafurmidine


Combination Drugs May be More Effective in Treating Myotonic Dystrophy

A recent review study suggested that combination therapies may be the most optimal pathway to treat myotonic dystrophy. A few years ago when the defective pathway for myotonic dystrophy was identified it was proposed that treatment would be easy to find as it was proposed that the clumping would be easy to defeat. This has proven not to be the case. Here is a summary from the study:

One potential strategy is a combination approach (e.g., di erent small molecule
combinations, small molecules plus ASOs, transcription inhibition plus RAN protein ablation, etc.)targeting multiple processes and allowing synergy in disease modulation. As proof of concept, a recent study reported that two previously characterized compounds that separately displayed ecacyin DM1 models, furamidine and erythromycin, displayed an even greater rescue of mis-splicing in
combination than expected from a mere additive e ect [110]. Importantly, this combination treatment yielded lower toxicity and fewer o -target e ects than when either drug was administered alone inDM1 patient and mouse models [110]. Hence, if combination treatments are a viable therapeutic strategy for treating DM, there are already many unexplored therapeutic avenues that could potentially hold promise. Given the number of small molecule therapies for DM on the horizon, it will be exciting
to follow their development. These studies will lay the groundwork for the eventual therapies for treating DM and will likely illuminate disease biology and treatment avenues for other microsatellite expansion disorders involving toxic RNA mechanisms.



Exercise May help Strengthen Muscles in Myotonic Dystrophy

A new study ( But only of two people) shows that it is possible to increase muscle strength in Myotonic Dsytrophy. This study seemed to show that the exercise program needs to be adopted to the individual so that they maintain the exercise program. The Muscle strength increase seems to be linked to how diligent the person followed the training regime. From the Study:

Our results suggest that muscular adaptations linked to muscle growth can occur in DM1 as demonstrated by the CSA increase of type I and type II myofibers. Training might also influence the distribution of myofibers, in favour of type II. The myogenic and inflammatory markers evaluated do not seem to be modulated by the training stimulus in our participants. Compliance to the program seems to be an important factor to consider. Patient’s preferences regarding training regimen should be considered in the perspective of personalized training/precision medicine. It should be noted that beyond the positive impact of training on muscle adaptations, it could also bring positive changes in other organ systems. Further studies comprising a higher number of participants and controls are needed to validate our findings and determine to which extent and how skeletal muscles of DM1 patients adapt to strength training.