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

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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.

 

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Study of Childhood and Congenital Myotonic Dystrophy

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Here is a recent study of issues with congenital and childhood myotonic dystrophy. It seems pretty comprehensive and has a lot of good information. The summary is below followed by the link to the full study. The study does not also provide information on the link to autism or autism spectrum disorders that many of the children have. The study does not go into depth on the adult form of the disease that follows as the children age and go through puberty. But a good basic review.

“In neonates and children, DM1 predominantly affects muscle strength, cognition, respiratory, central nervous and gastrointestinal systems. Sleep disorders are often under recognized yet a significant morbidity. No effective disease modifying treatment is currently available and neonates and children with DM1 may experience severe physical and intellectual disability, which may be life limiting in the most severe forms. Management is currently supportive, incorporating regular surveillance and treatment of manifestations. Novel therapies, which target the gene and the pathogenic mechanism of abnormal splicing are emerging. Genetic counseling is critical in this autosomal dominant genetic disease with variable penetrance and potential maternal anticipation,as is assisting with family planning and undertakingcascade testing to instigate health surveillance in affected family members.”

BELOW click on hyperlink for full study in PDF form.

Childhood Myotonic dystrophy 2015

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

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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

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Erythromycin Use in Myotonic Dystrophy Patients – Reduces diarrhea and more

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In 2002 a study in Sweden was conducted to see if a drug, Erythromycin would help improve the stomach emptying rate in patients with Myotonic Dystrophy. This study looked at 10 patients… here are a few key details:

“Gastrointestinal symptoms are
common among affected individuals and they may be of
considerable clinical relevance, e.g. abdominal pain, diarrhoea,
or anal incontinence. In a recent study we have found
that one-quarter of the patients considered their gastrointestinal
symptoms to be the most troublesome consequence
of the disease [3].”

The study showed that the drug erythromycin did not improve stomach emptying time but did help the majority of patients with diarrhea. In general the patients thought this drug improved their condition.

“Nevertheless, in general the patients
considered the treatment effective. This could be explained
by possible effects of the drugs on parts of the gastrointestinal
tract other than the stomach [15,16] due to the widespread
involvement of the gastrointestinal tract in MD
[9,17]. This assumption gains support in our study from the
fact that six out of 10 patients experienced reduced
symptoms of diarrhoea.”

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Watch your Weight!!! – It may affect your breathing!

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A recently published article has great information about weight and breathing. Simple conclusion: is that being overweight with Myotonic Dystrophy can affect your breathing and respiratory function. Since respiratory failure and pneumonia are big issue with Myotonic Dystrophy pay special attention to your weight!!! It also showed that a great majority of people with DM have an abnormal body composition. ITs important to keep the weight off but you also must see a nutritionist to insure that you are getting proper nutrition and to look at your body weight/mass/BMI. Here is the summary

InDM1 patients, overweight is an independent factor for predicting TLC, and contributes independently of FIV1. Because overweight isr elated to increased work of breathing and inspiratory muscle strength is reduced inDM1, the fatigue threshold will be reached sooner. Therefore, muscle fatigue and the onset of respiratory failure will develop at an earlier stage in overweight patients, especially during increased ventilator demand. Moreover, over half of DM1patients are overweight, and nearly all patients have an abnormal body composition. To develop interventional strategies for weight loss, it will be important to categorize the individual type of body composition. Hence, preventing the development of overweight inDM1 patients may result in delaying respiratory failure and mortality in DM1.

Click below on the link for the full study

Overweight Myotonic Dystrophy

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