Case study report of experimental use of approved FDA drugs to reverse myotonic dystrophy symtoms (DM1)

Encinitas, CA Two recent published studies reviewed the use of FDA approved drugs in Mice that reversed some myotonic dystrophy symptoms.  The mice showed improvement in muscle strength after a regime of using these approved rugs in appropriate dosages.

My son Chris has Congential Myotonic Dystrophy with a repeat count of about 1700. He is severely affected being non-verbal, cognitive delays, autistic spectrum disorder, and some muscle involvement. Chris also has the adult form of the disease as he reached puberty and has a level 1 heartblock, excessive sleepiness and other adult symptoms.

He has had 3 bouts of respiratory collapse. This initially involved a Hospital Stay, MSRA pneumonia. Within a very short period of time of initial symptoms he was in the ICU on a respirator and full dosages of heavy antibiotics including vancomycin. Recovery was uncertain and very slow. Tracheotomy was performed as weaning from the respiratory was difficult and dangerous. Full recovery was accomplished at 120 days. USA Hospital costs was approximately $750,000 for this. Two other bouts of respiratory collapse related to pneumonia occurred with similar outcomes.

We decided to pursue an experimental course of treatment with these FDA approved drugs due to concerns that he might not survive another bout of respiratory collapse.

In April 2016  we initiated a course of treatment on Erythromycin after consultation with pneumologist, cardiologist, cardiology expert in DM, and primary care Physician. The Primary care physician wrote the script for erythromycin. The cardiology team was involved as there is a contraindication for erythromycin with cardiac arrhythmia’s. The course was 2X daily 125mg of Erythromycin orally.

In May 2016 we added a daily dose of 80 Mg of Ketoprophen as this drug was found to have a positive effect on mice as well in ameliorating the myotonic dystrophy symptoms.

Results: We did not use any formal metrics in evaluating the results of the trials. The main reporting point was discussions with caregivers to see if there was any improvement in cognitive or strength related improvement in the patient. These conversations were all convergent in :

Overall Muscle strength               NOT IMPROVED
Overall Cognitive Abilities             NOT IMPROVED
Chest Congestion                        DECREASED SOUNDS
OF SECRETION CLEARING

# of Pneumonia Infections           IMPROVED

Overall the results of this 8 month trial did not replicated the information in the two mice studies. There was no increased muscle strength noted by caregivers. There did seem to be a significant improvement in clearing secretions in the lungs which is a critical factor in this patients Quality of Life (QOL). No Pneumonia infections were reported. this is a significant improvement over the last 12 months.

Discussion: Overall it appears that this therapy may have had an positive  impact on the patient. Overall the results of this one case did not replicate the studies that used mice in terms of improvements in muscle strength. this may be due to a number of reasons including dosing strength. It could also be that the mice that are created to have myotonic dystrophy are not the ideal method to test drugs the the DM in these mice may be more susceptible to disruption that the actual DM gene in human patients.

Patients with Congenital Myotonic Dystrophy and certain other patients (older than 57) are currently excluded from clinical new drug trials. Myotonic Dystrophy is slowly progressive until an exponential event occurs. Because of the risk of sudden death and pneumonia with these cases is ongoing looking for alternatives to reduce risk of death may be warranted by patients health care team.

 

Phenylbutazone & NSAIDS – Another potential treatment(s) for Myotonic Dystrophy

Orudis KT

Another paper has been published and revealed another potential treatment for myotonic dystrophy, Phenylbutazone PBZ.. Interestingly this study was also done in Japan………… now a hotbed of repositioning drugs for treatment of myotonic dystrophy.   some info from the study

“Using the drug repositioning strategy, we found that PBZ markedly elevated MBNL1 expression in myogenic cells(Fig. 1 and Supplementary Fig. S1) as well as in skeletal muscles in HSALR mice model (Fig. 2 and Supplementary Fig. S2). PBZ mitigated muscle pathology (Fig. 2d,e) and improved the running wheel activity and grip strength
in HSALR mice (Fig. 2c and Supplementary Fig. S2d).”

This summary above  showed that in mice this drug helped mice with myotonic dystrophy run on the wheel better and had better grip strength. More info below

PBZ is an NSAID with anti-inflammatory, antipyretic, and analgesic activities. PBZ was approved in humans for rheumatoid arthritis and gout in 1949. Although incidental adverse effects of fatal liver disease and aplastic anemia markedly lowered the use of PBZ, PBZ is still used as an alternative drug for ankylosing spondylitis32,33.
Interestingly, another NSAID, ketoprofen has been reported to suppress CUG-induced lethality in Drosophila34, and we also found that 50 μ M ketoprofen upregulated the expression of Mbnl1 mRNA 1.2-fold in C2C12 cells, which was lower than the 1.3-fold increase of Mbnl1 mRNA by 50 μ M PBZ (Supplementary Fig. S6). Ketoprofen
and some other NSAIDs may have beneficial effects on a mouse model of DM1, as well as on DM1 patients.

Editors Note: This drug (PBZ) approval was removed for humans in 2003 in the USA and Canada. It is available for use in animals only. The drug Ketoprofen was not studied in depth but is an approved NSAZID drug in the USA. We have choosen the image of Ketoprofen as this is an approved drug in the USA.

Full study is Here.. Phenylbutazone Treatment DM1 mice

FDA approved Chemotherapy Drug Might Treat Myotonic Dystrophy

In a stunning development The Berglund lab in Gainsville, FL has identified a potential treatment of myotonic dystrophy of a Chemotherapy drug Actinomycin D. In Both Cells and mice that were created to have myotonic dystrophy the drug used at or below levels that are used in human chemotherapy pushed back the Foci that are associated with the disease.

In theory this might be a treatment for myotonic dystrophy. This has not been tried in humans and would be highly risky but for people near end of life this may be a vector for them and their doctors to consider.

Researchers have previously identified what they think is the cause of the disease.In Myotonic Dystrophy the repeat expansion mutation is made into RNA but it does not get out into the cytoplasm. It remains trapped in the nucleus where it sticks to various proteins and appears as spots or foci that can be observed down the microscope. Because these proteins are stuck to the repeat RNA they cannot perform their normal functions correctly within the cell.

Researchers have found that to make progress with this disease, they need to “unstick” the proteins. This drug appears to do this in mice and cells.

Previously to the publication of this article there was no even theoretical treatment available. There are several drugs in development but this takes years of development. For those near end of life with this disease there is now a potential treatment. A copy of the article is here. This is something you may want to discuss with your medical team. Its untried and potentially risky with side effects. More information will be available shortly.

Myotonic Dystrophy Treatment

Please note the study is very technical. We are not recommending this to anyone but bringing all the current information to your attention

Full Phase I Drug Trial Recruiting for Myotonic Dystrophy (DM1)

This week ISIS pharmaceuticals announced the commencement of recruiting for Phase I of the Myotonic Dystrophy Drug Trial. This is tremendous news for the myotonic dystrophy community. The promise of scientific research to define the DNA site, identify the cause of the disease,  then begin to develop treatments that would reverse the problems in the cell are culminating  to the promise of hope for all that suffer from this horrible affliction.

If you want to participate in this study you must act quickly and contact the centers that are conducting the research. Find the closest location and contact the person via email or phone. You must meet all (meaning all) the qualifications for the trial. The full information is on CLINICALTRIALS

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ISIS Announces Phase I trials For Myotonic Dystrophy Type 1 Drug

Happy Days! A clinical Trial is going to start on Phase one of Myotonic Dystrophy Drug. That means that a small number of patients in the US usually under 50 will get a chance to try the drug. The purpose of the Phase I trial is to

Try out the drug
Find an optimum dose
Assess Safety of Drug

More on what a phases of clinical testing mean  (From MD Anderson site)

What are Phase 1 Clinical Trials?

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