Oculopharyngeal muscular dystrophy
Oculopharyngeal muscular dystrophy (OPMD) is a rare type of muscular dystrophy which primarily affects two small muscle groups – the muscles around the eyes (oculo) and the muscles used for swallowing (pharyngeal). Many years after diagnosis some muscle weakness in the limbs may also be noticed. It is a late onset condition with symptoms usually developing when a person is over the age of 50.
OPMD affects about 1 in 100,000 people worldwide but it is more common in some populations such as French Canadians, Bukhara Jews in Israel and Hispanic New Mexicans. For example, it has been reported that 1 in 1000 French-Canadians in Quebec have OPMD.
In this factsheet:
• What are the symptoms of OPMD and how is the condition managed?
• What causes OPMD?
• Is OPMD inherited?
• How is OPMD diagnosed?
• What research is being done?
• Further information
What are the symptoms of OPMD and how is the condition managed?
The first symptom of OPMD to appear is usually drooping of the eyelids due to weakness of the muscle that normally lifts up the eyelid. The medical name for this is “ptosis”. Another symptom that appears early is difficulty swallowing. The medical name for this is “dysphagia”. These problems get worse very slowly over many years.
Sometimes mild ptosis can be managed with glasses fitted with fine metal bars (ptosis props) that lift up the drooping eyelids. However, eyelid surgery is generally recommended when drooping eyelids interfere with vision or when neck pain becomes a problem due to constantly tilting the head up to see below the eyelids. This surgery can be very successful.
People with OPMD initially have problems mainly with swallowing solid and dry foods. A dietician can advise on foods that are easier to swallow and which reduce the risk of choking, and a speech therapist can prescribe exercises to do at home to improve swallowing. Swallowing difficulties progress slowly to a point where swallowing liquids, even saliva may become a problem and there is a danger of inhaling food or drinks into the lungs (aspiration) which can cause chest infections. As swallowing gets more difficult a lot of weight may also be lost and there is a risk of malnutrition. Along with swallowing difficulties, a “breathy” quality of the voice also may occur.
Currently there isn’t a way to increase the strength of the swallowing muscles but it has been found that reducing the resistance in the throat that the food has to push past can help. This involves weakening or stretching the muscle that surrounds the throat just above the esophagus which is known as the “cricopharyngeus” or CP muscle. There are several ways to do this:
• “Cricopharyngeal dilation” – a simple procedure which involves stretching of the CP muscle. This can give improvement which lasts up to a year.
• Injections of botulinum toxin (Botox) into the throat to relax the CP muscle. This can offer improvement which lasts for 3 to 4 months.
• “Cricopharyngeal myotomy” – a minor surgical procedure which involves cutting the CP muscle internally. This is longest lasting, but most invasive option and is known to last about three years on average.
If swallowing can’t be improved to an adequate level and there is a risk of malnutrition or aspiration, a gastrostomy can be performed so that feeding can occur via a tube directly into the stomach. A dietician can advise on supplements if necessary to help maintain adequate nutrition.
After many years some limb weakness may be noticed, first around the shoulders and later around the hips. This weakness is usually relatively mild and doesn’t cause major disability, but can occasionally be severe and disabling. Physiotherapy can help to keep the muscles strong and supple for as long as possible. Equipment such as leg braces, a cane or walker may be helpful and eventually a wheelchair may be required by some people. An occupational therapist can help with techniques to cope with upper arm and shoulder weakness and ways to manage difficult activities like rising out of chairs.
Keeping fit and active is just as important for people with OPMD as the general population, if not more so as it may help to strengthen muscles and possibly slow progression of weakness. Research into the benefits of different types of exercise for OPMD is ongoing, but it is generally recommended to take regular gentle exercise. A physiotherapist should be able to give advice on a suitable exercise program.
What causes OPMD?
OPMD is a genetic condition caused by the presence of a mistake in the DNA (which is often referred to as a ‘mutation’). The mutation is in a gene called ‘polyadenylate binding protein 1’, or PABPN1. This gene contains the instructions for making PABPN1 protein which has an important role in the nucleus or control centre of the cell. In OPMD there is an extra piece of DNA code in the gene and as a result the PABPN1 protein is slightly longer than normal. How this causes the symptoms of OPMD is not fully understood but it is thought that the longer PABPN1 protein folds incorrectly and forms clumps (also known as “aggregates” or “inclusions”) which impair the normal function of muscle cells and leads to the cells dying.
Is OPMD inherited?
Yes, OPMD is inherited in a pattern known as “autosomal dominant”. Autosomal means that it affects males and females equally as the genetic change is not located on one of the sex chromosomes (X and Y). Dominant refers to the fact that just one altered PABPN1 gene, passed from one parent to their offspring, is sufficient to cause disease symptoms. The altered gene over-rides or dominates the normal copy inherited from the other parent. Each affected person usually has one affected parent. The chance of somebody inheriting the condition from a parent with the condition is 50 percent, or 1 in 2.
There have been a few rare cases of OPMD reported that are inherited in an “autosomal recessive” pattern.
How is OPMD diagnosed?
OPMD is suspected based on symptoms – eyelid drooping (ptosis) and swallowing difficulty (dysphagia). Tests known as videoendoscopic and videofluoroscopic swallowing studies may be necessary to detect swallowing problems. There is usually also a family history of the condition. The diagnosis is then confirmed by genetic testing of a blood sample. Muscle biopsies are usually not required.
What research is being done?
The genetic fault that causes OPMD was identified in 1998 and since then a lot of progress has been made in understanding how it causes the symptoms of OPMD. As a result, several potential treatment approaches have emerged, some of which are described below.
Reducing protein aggregation and cell death
Research groups around the world are searching for ways to treat the effects of the genetic change that causes OPMD. They aim to reduce the clumping or aggregation of the abnormal PABPN1 protein and/or prevent muscle cells dying. Encouraging results have been reported from the testing of various drugs and chemicals in human cells grown in a petri dish in the laboratory or in mouse or fruit fly models of OPMD (please see table below).
BioBlast Pharma is currently conducting a phase 2 clinical trial in Israel and Canada of a drug called Cabaletta which is based on trehalose. Initial results released in September 2014 showed that the drug appears to be safe (11 OPMD patients treated intravenously for 7 weeks). The trial aims to test Cabaletta in 60 people with OPMD for 28 weeks in order to determine if it is safe and if there is any indication that it might be able to slow the progression of the condition. More information about the trial is available on www.clinicaltrials.gov
A small clinical trial in France has shown that transplanting cells from unaffected muscles into the throat may help with the swallowing difficulties that affect people with OPMD. Twelve people with OPMD were enrolled into the study and a biopsy was taken either from their neck (sternocleidomastoid muscle) or upper thigh (quadriceps). This muscle sample was sent to a laboratory where cells called myoblasts – which have the ability to develop into muscle fibres – were isolated and grown until there were enough cells for the transplant. The patients then underwent a cricopharyngeal myotomy operation (see above). During this procedure the trial participants also had their own myoblasts injected into the pharynx.
The trial participants were followed up for two years after the transplant and it was found that swallowing improved for all twelve participants and remained stable. Longer term follow-up is also ongoing and the results appear to be positive, whereas people with OPMD who only have the cricopharyngeal myotomy surgery generally initially improve but then deteriorate. The procedure was also well tolerated which is encouraging news for people with OPMD.
However, it must be remembered that this was only a small trial and due to the rarity of the condition it was not feasible to include a placebo group for comparison – that is, patients who did not receive the myoblast injections. Valuable information on the best way to perform the transplant was gained in this study which will be used to plan a larger trial to assess in more detail the benefit of myoblast transplantation for OPMD before it can be brought into clinical practice.
It also must be noted that the transplanted cells contain the genetic mutation that causes OPMD so it is expected that these will also eventually succumb to the condition, but since it is a late onset condition that progresses slowly it is hoped that this might still be a viable treatment option.
You may be interested in registering with the OPMD patient registry, based in New Mexico. Patients outside of the USA can register by downloading the registration form, filling it in and posting it back.
A patient registry is a database that contains information about patients with a particular condition. Clinical trial organisers and other researchers use this (anonymous) information to learn more about the condition and plan clinical trials. If a clinical trial were to start, the registry would be used to contact suitable potential participants and invite them to take part. Patient registries are also a useful source of information for patients and their families as regular newsletters are sent out. You can find out more about patient registries on our website.
NOTE: Research is moving forward at a fast pace, so this research summary may not be up-to-date at the time of reading.
• Read about the research MDA funds which aims to reduce inflammation in the muscles and improve muscle regeneration
• For definitions of any terms that you are not familiar with please take a look at our glossary
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Revised 14 March 2018
Aida Abu-Baker, Guy A. Rouleau. Oculopharyngeal muscular dystrophy: Recent advances in the understanding of the molecular pathogenic mechanisms and treatment strategies. Biochimica et Biophysica Acta 1772 (2007) 173–185
Capucine Trollet et al. Oculopharyngeal Muscular Dystrophy. GeneReviews (internet) Initial Posting: March 8, 2001; Last Update: February 20, 2014.
Sophie Périé et al. Autologous Myoblast Transplantation for Oculopharyngeal Muscular Dystrophy: a Phase I/Iia Clinical Study. Molecular Therapy vol. 22 no. 1, 219–225 Jan. 2014.