Potential Myotonic Dystrophy Drug Fails! – Ionis Myotonic Dystrophy Drug fails to reach minimal therapeutic value

In a instant news email the Myotonic Dystrophy Foundation (MDF) released information that the Ionis Pharmaceutical Drug DMPK-2.5Rx research project has been canceled. The drug DMPK-2.5Rx did not work, and did not get the correct amount of therapeutic drugs into the cells of the patients with myotonic dystrophy. The company may still continue research on a more potent combination but the current trial is halted.

This is hard to hear news for the myotonic community. This is the second drug in development to fail. This new drug is part of a number of new generation of interest drugs  in trying to find a drug to treat the disease. There are still a number of drugs in development but the Ionis one was the most advanced. Perhaps the information in this trial will be of help to the other drugs in development.  For those in the late stages of the disease the length of time to find a treatment that is FDA approved in unlikely now.

There continues to be some “off label” treatments including erythromycin and some NSAIDS as well as Actinomycin-D but none have had any proven human effect.

More information below.

Ionis Pharmaceuticals Reports on
DMPKRx Phase 1/2 Clinical Trial

Ionis Pharmaceuticals recently concluded a Phase 1/2 clinical trial to evaluate IONIS-DMPK-2.5Rx in myotonic dystrophy patients. IONIS-DMPK-2.5Rx was designed to target the toxic DMPK RNA in muscle that is responsible for myotonia or muscle dysfunction in DM1 patients. The clinical trial used dose escalation to assess safety and explore biomarkers for target engagement in muscle biopsies.

Ionis reports that small but encouraging trends in biomarker and splicing changes were observed during the trial, and that this study provided a much better understanding of how future clinical trials and improved clinical endpoints may be used. However, drug levels measured in biopsy tissue from trial participants indicated that the amount of target engagement would not achieve the desired therapeutic benefit to treat this disease.

Without the desired drug levels in muscle, Ionis has decided not to advance IONIS-DMPK-2.5Rx. It will instead pursue the discovery of a more potent drug to target DMPK using new muscle-targeting LICA chemistry made at Ionis.

The company sincerely thanks everyone in the DM community that participated in the study – patients, caregivers and physicians, noting, “we are committed to the DM patient community and we hope to advance a new, more potent drug into development that will benefit people living with DM1.”

Ionis invites DM community members to submit questions regarding the above announcement via this email address. MDF will collect questions through January 12th and then work with Ionis to get answers out to the community as soon as possible.

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 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.


New Company Atricode Formed to Pursue Myotonic Dystrophy Drug Development (MDI16)

A highly promising Compound has formed the basis for a new pharmaceutical company. This company is Called Atricode and is based on compounds that have been researched at University of Southern California to treat and cure Myotonic Dystrophy. Sita Reddy’s Lab has been instrumental in moving these potential treatments (MDI16) for Myotonic Dystrophy. The lab and company has recently been awarded a $90,000 grant through a competitive process. More about the grant:

2012 USC Ideas Empowered Program Grant: $90,000

Atricode is developing treatments for rare diseases. The lead indication, Myotonic Dystrophy Type 1 (DM1,) is a devastating genetic multisystem disorder with no available treatment or cure. This team identified highly potent and selective small molecule leads that rescue DM1 pathology in patient myoblasts and in DM1 mouse models. The team joined forces with experienced entrepreneurs to form a start-up company that moves the drug candidates towards the clinic. The drug candidate could be the first therapy to treat this devastating disorder and the Ideas Empowered funds are critical for the selection of the lead candidate for clinical development and to support fundraising efforts.

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Patient Management



Summary of the lecture by Christine E.M. De Die- Smulders MD  of the University of Maastricht at the yearly meeting organised in October 1996 by the “Werkgroep Dystrophia Myotonica” for patients and other people involved in myotonic dystrophy. This lecture was meant for the new participants of  this annual meeting.




Myotonic Dystrophy (DM) is a  relatively frequently occurring, hereditary muscular disorder. Characteristic symptoms are myotonia (muscle stiffness due to muscles failing to relax properly)  and slowly  progressive muscle weakness, especially of the face-muscles, the throat- and neck-muscles and the muscles in the fore-arm and lower part of the legs. Other organs may also be affected. This manifests itself in  symptoms  as cataract, irregular heart-beat, slowness, loss of initiative and infertility in males. There may be a considerable variation in the severeness among patients. The age at onset of the disorder and the character of the symptoms are highly  depending upon the length of the expansion of the CTG repeat in the DM-gene.


Classification in four types according to age and main symptoms


1              Mild type

2              Adult (= classic) type

3              Childhood type

4              Congenital type  


Adult type (2)

Age at onset: 12 – 50 years


Initial symptoms:

Muscle weakness

 Later symptoms:

Increasing muscle weakness


Slowness, loss of initiative

Defects in several organs


The adult (classic) type is the most frequently occurring type. Myotonia and muscle weakness develop from puberty till the age of 50. Myotonia is a painless muscle stiffness, notably affecting the hands after a firm grip. Complaints are: difficulties with letting loose a door-handle and after shaking hands or cramp when wringing out a cloth, especially in wintertime. The stiffness disappears spontaneously after a short time. Cold can evoke or stimulate this stiffness. Most patients are slightly troubled by myotonia and will not complain spontaneously about it.

The muscle weakness starts gradually and it may last for years before a patient consults a doctor. Weakness of  face-muscles appears at an early stage: The eyelids hang down and when the patient is asleep part of the white of the eye stays visible. It is no longer possible to laugh broadly. Speech gets indistinct and it looks like the patient speaks “through his nose”. The temples shrink by the jaw-muscles getting thinner. The weakness of the bending muscles of the neck is often pronounced. Patients cannot raise their heads when lying down. The loss of power  in the muscles of the fore-arm and hands makes together with the myotonia the hands clumsy. Regarding the muscles the lower part of the legs especially the raising of the feet is reduced: The patients start shuffling, stumble over minor roughness’ and fall more frequently. Sometimes next to these there are less specific complaints such as fatigue, lack of spirit, stomach-complaints or swallowing problems.

In a later stage of the disease the muscle weakness will increase and the muscles of the upper-arm and upper-part of the leg will be affected. Most patients however stay mobile if their radius of action is reduced till in and around their homes. Seldomly patients get bound to a wheelchair.  


Mild type (1)


Age at onset: over 50 years


Initial symptom:


 Later symptoms:

Muscle weakness


The mild type starts after the age of 50. Most patients only get cataract. In a later stage mild muscle weakness and myotonia may appear. If the illness is unknown in the family it is seldom recognised that the cataract is part of a muscle-disease.


Congenital type (4)

During pregnancy:

Much amniotic fluid

Reduced fetal movements


At birth:

Muscle weakness

Problems with breathing and swallowing


Weak  face-muscles


First year of life:

Muscle weakness decreases

Baby learns breathing and drinking by him/herself

Slower development
 After the first year of life:

Learn to walk  (2 – 5 years of age)

Learn to speak (sometimes indistinctly)

Get cleanly

Problems with learning


Inflammation of the ears

Problems with bowels



The congenital type shows severe muscle weakness and decreased muscle strength at birth which leads to problems with breathing and swallowing. During pregnancy there is much amniotic fluid (because the baby does not  swallow) and the mother feels less stirring of the baby. A number of babies die because of breathing problems. If they survive they recover considerably from the muscle weakness during the first years of life, because of growth of the muscles. Indeed these children often have the characteristic tent-shaped mouth. The patients show a retarded motor development, which needs treatment by a physiotherapist. A majority of the children learns to walk between the age of 2 and 5 years. Bowel cramping and constipation often occur, just like inflammation of the inner ears. Besides there are problems with speaking, among others due to weakness of the palate. At adult age muscle stiffness and muscle weakness occur.

The mental retardation with this type is often mild to moderate. The children learn to speak and learn to take care of themselves, but mostly they do not learn to read and write. It is important to test the child in time and to choose the right type of school based on the testresults. Most children need special education. Take care that the child is not underestimated. Factors which may influence underestimation are the facial muscle weakness, the problems with speaking, poor hearing and slowness.

The congenital type is almost always passed on by an affected mother, seldom by an affected father.