Dynacure news 2020

Clinical trial recruitment

Unite-CNM, the Dynacure sponsored clinical trial of their antisense product, DYN101, began recruiting in early 2020 at sites in the UK, Belgium and Netherlands, with an additional five European sites to follow.

Pre-clinical studies have shown that ‘turning down’ Dynamin 2 can reduce the symptoms of centronuclear myopathy, so the clinical trial will evaluate DYN101 for safety, tolerability, pharmacokinetics (how the drug works around the body) and preliminary efficacy (the effect on symptoms). It will include approximately 18 patients, who are over 16 years of age and have XLMTM or DNM2 mutations.

Further information about the trial, including inclusion and exclusion criteria, site location, recruitment status and contact details can be found below.

March 2020

Dynacure announces first patient dosed in phase 1 / 2 ‘UNITE-CNM’ Study of DYN101 for the treatment of centronuclear myopathies 

In March, Dynacure announced that a patient had been dosed with DYN101. This milestone marks the first time any company has dosed a CNM patient with an antisense medicine.  For further information view the press release below.

April 2020

Dynacure Announces €50M ($55M) Series C Financing

In March, Dynacure announced €50M ($55M) Series C Financing. The funding will support ongoing Phase 1 /2 ‘Unite-CNM’ study of DYN101 in patients with centronuclear and myotubular myopathy.

May 2020

Dynacure announce that circulating myostatin levels are altered in centronuclear myopathy mice and patients and myostatin levels respond directly to DNM2-therapy in mice. Myostatin is now currently being explored as a biomarker in our Unite-CNM clinical trial.

July 2020

In July the first two patients were dosed with investigational drug DYN101 in UNITE-CNM trial and Dynacure CSO Belinda Cowling was also named a finalist for the EU Prize for Women Innovators 2020.

Dynacure also received rare pediatric disease designation from the US Food and Drug Administation for DYN101 for myotubular and centronuclear myopathies.

Dynacure logo.

Dynacure news 2019

April 2019

Clinical trial application (CTA) for DYN101 approved

In April the UK regulatory authority – the Medicines and Healthcare products Regulatory Agency (MHRA) – approved the Clinical Trial Application (CTA) for DYN101 – Dynacure’s antisense product in development for centronuclear myopathy. This antisense drug has been developed in collaboration with Ionis Pharmaceuticals who have an excellent track record in creating these drugs and is built on the DNM2 work of Jocelyn Laporte and his team at IGBMC in Strasbourg.

Dynacure receives research grant

Also in April, Dynacure announced they had been awarded €450,000 research grant funding from a French organisation, Bpifrance, to help them speed up current development plans for their lead project (an antisense compound/drug named DYN101). The funds will be used to see if it will help improve muscle strength in patients with centronuclear myopathy; support them to find out if they can potentially expand the application of DYN101 antisense therapy to help treat other human diseases and help them discover new measurements (known as biomarkers) which can prove the effectiveness of using this drug to treat patient symptoms.

July 2019

Dynacure receives orphan drug designation in the EU for DYN101

In July, Dynacure announced that the European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP) had granted Orphan Drug Designation to DYN101 for the treatment of centronuclear myopathies (CNM). DYN101, an antisense medicine.

The European Commission grants Orphan Drug Designation in the EU to products that treat a life-threatening or chronically debilitating condition affecting no more than five in 10,000 people in the European Union (EU) and where no satisfactory treatment is available.

“With Orphan Drug Designation in the EU, we have achieved a significant regulatory milestone in our development plans for DYN101 and we look forward to working with the EMA as we progress,” said Stephane van Rooijen (M.D. MBA), Chief Executive Officer of Dynacure.

Leen Thielemans, Chief Development Officer of Dynacure, added, “Orphan drug status is granted to investigational therapies that are expected to make a significant impact on patient care and we believe DYN101 holds great promise to treat a broad range of centronuclear and myotubular myopathies. The formal designation has been granted based on compelling preclinical data in several forms of CNM. As we prepare to initiate the UNITE-CNM clinical study, we also intend to expand the use of DYN101 to explore additional indications where the overexpression of DNM2 is a disease-driving factor.”

September 2019

Phase 1/2 clinical trial pipeline for DNM2 and MTM1, plus patient questions answered

In September 2019 at the request of CNM patient organisations, Dynacure provided  information on their ongoing work to bring their investigational product DYN101 through clinical development and approval for use in the treatment of CNM patients with MTM-1 or DNM2 mutations.

Please be aware that as the company are still in the phase of developing DYN101, they are limited as to what they can present according to regulations around the world. The scientific background is complex – it has been simplified as much as possible to be understandable and there is a glossary at the end that tries to explain some of the terms used.

Belinda Cowling awarded Prix Scientifiques 2019 (Scientific Prize) from the University of Strasbourg. 

Also in September Dynacure CSO Belinda Cowling was recently received the Prix scientifiques 2019 (Scientific Prize) from the University of Strasbourg. Belinda was recognized for her research publications and success in academic/industrial partnerships.

Belinda Cowling

Belinda Cowling receiving Prix Scientifiques 2019 (Scientific Prize).

October 2019

Dynacure presents new preclinical results on muscle targeting with antisense oligonucleotides

In October Dynacure, presented New Preclinical Results on Muscle Targeting with Antisense Oligonucleotides at the 24th Annual International Congress of the World Muscle Society (WMS).

Preclinical mouse work has shown ASO-mediated DNM2 knockdown can efficiently correct skeletal muscle defects due to loss of MTM1, providing an attractive therapeutic strategy for this disease. Dynacure scientists presented new preclinical data investigating skeletal muscle targeting of DNM2 reduction in mice with new palmitate-conjugated antisense. Effective muscle targeting will be an important step in translation of this approach to the clinic for patients.

“We are pleased to present new preclinical results at World Muscle Society that support our clinical approach of modulating DNM2 to treat CNM as well as data from a natural history study,” said Belinda Cowling, Chief Scientific Officer of Dynacure.  “In preclinical models, we’ve demonstrated that antisense oligonucleotide knockdown can efficiently correct muscle defects in certain genetic forms, XLCNM and ADCNM, which represent a large portion of the treatable patient population.  This provides an effective therapeutic strategy to treat several forms of centronuclear myopathies due to the mutations in different genes.  In addition, the data measuring clinical changes over time collected from patients enrolled in the ongoing European natural history study will continue to inform our clinical plans.  We look forward to evaluating our lead therapeutic candidate DYN101 in patients with the initiation of our Phase 1 / 2 UNITE-CNM study.”

Dynacure logo.

Research news 2017

During 2017 The Information Point reported on a number of research stories and these can be found below.

Characterisation of a new class of congenital myopathies

With the support of funding from the Myotubular Trust, the team of Jocelyn Laporte, have identified a novel gene, named CACNA1S, implicated in centronuclear myopathy. This is a very important breakthrough as it highlights potential new avenues for research.

High-throughput sequencing of the DNA of 11 patients who did not have a genetic diagnosis for their centronuclear myopathy, revealed to researchers that all of the patients had mutations in the CACNA1S gene. Surprisingly, these mutations are widespread in the gene and are either from recessive or dominant transmission.

The gene CACNA1S was already well studied because of its implication in other diseases but this is the first time the gene has been associated with a myopathy and will give hope to families who currently do not have a genetic diagnosis.

Centronuclear myopathy: towards the development of a therapy 

After identifying Dynamin 2 as a potential therapeutic target in congenital myopathies, the team of Jocelyn Laporte at the IGBMC has managed to specifically modulate the level of this molecule and to cure almost all signs of disease. These results published on 7 June 2017 in the journal Nature Communications provide excellent perspectives for therapeutic development.

The centronuclear myopathies, which include centronuclear myopathy (CNM) and myotubular myopathy (MTM), are rare genetic diseases characterised by a very disabling muscular weakness and early death. There are several genetic causes of CNM, in particular mutations of genes coding for myotubularin (MTM1) or dynamin2 (DNM2), proteins that regulate the organisation of muscle fibres.

Three years ago, researchers from Jocelyn Laporte’s team demonstrated in myopathic mice lacking MTM1 that decreasing the level of DNM2 by genetic cross improved the clinical signs of the disease (Cowling et al., 2014). Animals that previously died of the myopathy by two months of age, instead survived two years, a normal lifetime for mice. This proof-of-concept published in 2014 identified DNM2 as a new therapeutic target, generating a large interest for therapeutic development. This required however that an injectable compound targeting DNM2 could be developed for clinical use.

Hichem Tasfaout, Belinda Cowling and Jocelyn Laporte at the IGBMC have collaborated with Ionis Pharmaceuticals, a world leader in antisense oligonucleotides (ASO) technology. ASOs are synthetic RNA fragments that can bind very specifically to target messenger RNAs to promote their degradation.

These researchers have demonstrated that injections of ASOs targeting DNM2 messenger RNA in myopathic mice effectively reduced the level of DNM2 and restore muscle function, either to prevent development of the disease (injection before onset of symptoms) or to revert the signs of the myopathy (injections in a severely affected animal). Treatment resulted in improved muscle function and increased lifespan, using a chemistry and dose that can be translated to patients.

These very promising results contributed to the creation of the start-up company Dynacure, which aims to transform this approach into clinical trials. This study was financed by SATT Conectus and the National Research Agency (ANR).

Myotubular Trust 2017 research grant award

In October 2017 the Myotubular Trust announced its 2017 grant award to Dr James Dowling of Sick Kids Toronto. The grant will allow Dr Dowling and his team to investigate the effectiveness in myotubular myopathy of two existing drugs currently licensed for use in children who have other conditions which have been identified by Dr Dowling’s team as showing encouraging signs of improving the symptoms of myotubular myopathy.

This three year grant from Myotubular Trust and supported by our friends at ZNM – Zusammen Stark! will allow Dr Dowling and his team to investigate the effectiveness of these drugs, either alone or to complement other therapies. Repurposing medicines that are safe and have been used and studied in children is a very exciting goal for rare diseases. We are delighted to be making our 2017 grant of £216,000 to Dr Dowling to pursue this promising project.

“Because these drugs have previously been used in children, we feel that the pathway for clinical development and testing of them can be feasibly accomplished in a timely and cost effective manner” – Dr Dowling.

Continuation of previous grant – PI(3)P levels

During the course of this grant, Dr Dowling’s laboratory will also continue to develop on previous awards by the Myotubular Trust. Loss of MTM1 results in the accumulation of a lipid called PI(3)P in someone with myotubular myopathy. This project will continue to develop inhibitors of PI(3)P that work well in humans and can be translated to clinical use.

“Furthermore, we believe these therapeutic strategies may be applicable to the broader range of patients with centronuclear and myotubular myopathy” – Dr Dowling.

Further information

To read more about this research see below.

Researchers in the Dowling laboratory


How I Met Your Father

This article first appeared in The Information Point newsletter Our World in 2016 when Aminah Hart told us about her book How I Met Your Father. Aminah, the mother of three children, sons Marlon and Louis who had myotubular myopathy and daughter Leila, then three years old, born after Aminah underwent IVF using anonymous donor sperm. Aminah told the Information Point about her life, her boys and the unconventional way she came to have her daughter and fall in love with Leila’s father Scott. 

Book launch

What made you decide to tell your story

The ABC’s Australian Story did a documentary about my life in 2014. After it aired, three different publishers approached me asking if I’d like to write a memoir and I thought it would be a lovely way to pay tribute to my deceased sons, Marlon and Louis and create a lasting record for my daughter Leila to read when she’s old enough given that she has quite a big back-story to her life and came into the world in quite an unconventional way.

Aminah and Marlon.

Did you have any goals for the book when you began writing it

I was very fortunate to be approached by publishers rather than the other way around. Initially I was offered a ghost writer but I am very protective of the story of my childrens lives and so I very much wanted to tell the story in my own voice and my own way although I’d never written for public consumption before. Ultimately I was offered an advance to write my story and the publisher I chose, Louise Thurtell at Allen and Unwin, was very supportive in her encouragement at the times when I worried I couldn’t do it. She assured me I’d find my voice and once I did the story would flow. This turned out to be true although it took a month of procrastination and avoidance before I got started in earnest.

Aminah and Louis.

How long did the book take to write

I signed the contract with Allen and Unwin in December of 2014 with a manuscript deadline of July 31st. I procrastinated for all of January 2015 then finally started writing on February 1st. I delivered the last section of the manuscript on July 30th, one day early!

Aminah and Leila.

Did you have a particular time of day you wrote, a number of words or chapters you wrote each day, a place you liked to write

Once I got going, I treated it like my full time job and wrote every day, sometimes for up to ten hours in a day. Sometimes the words wouldn’t come and I’d give myself a break then come back to it when I felt able.

Daddy and daughter.

How did you go about putting the book together

Thankfully I had kept fairly detailed diaries since I’d left home in Australia, for London in 1995. I also kept complete journals during both of my sons lives that chronicled every detail of our days as I never wanted to forget. I have a good memory but I would never have remembered the finer details without those records, especially the more traumatic times as they had been tucked firmly away in my emotional archive in order to cope and move forward. It was incredibly emotionally gruelling revisiting some of those tragic and painful times in my life.

Aminah, Scott and Leila.

The book is very honest and there are parts which must have been hard to write – how did you deal with writing the hard parts

It was a very steep learning curve. My mind works in a linear and methodical way having spent so many years in advertising agencies managing deadline driven projects, so I expected to start the book at the beginning and work my way through it chronologically. However the part before I was born relied on my mother’s diaries and I discovered they were written in shorthand which I can’t read so she had to transcribe those first meaning I couldn’t start where I had hoped. So I tried moving on the period of my life where I first got married and had my first son Marlon but the story wouldn’t come out. This was when I realised how I had wrapped up the saddest parts of my life tightly in little boxes and put them away in the recesses of my mind. At first I wasn’t ready to access those memories at all. Eventually I thought to myself, start with the happy part, the part where I had my healthy daughter Leila and then met her dad and fell in love. So I basically started at the end and wrote the whole thing back to front.

Once I’d had the reassurance from my publisher Louise that the quality of my writing was good, that gave me the confidence to delve into the sadder parts of my life story and put them on the page for public consumption. As you can imagine there were lots of tears and snot at times and I simply had to down tools, take myself for a long walk and let the memories filter back through my mind, as painful as that was. Hopefully it helped make the story authentic for readers as the emotions on the page are very real.

The media have focused on the back to front nature of your relationship with Scott and it is a lovely way to start, knowing the happy ending and working back, however, the book covers much more than that – how would you describe the book and what would you like readers to take from the book after they have read it

For me, it’s primarily a story of motherhood. Both my mother’s and my own. Our journeys to and of motherhood, the challenges, the potholes along the way but overwhelmingly of maternal love and lengths we will go to to protect and nurture our children who can bring the greatest of joy and deepest of sorrow to our lives. It is also the story of me. The racism I faced as a child and the strong and determined black woman I became despite it, nurtured by and within a loving family who gave me the tools I would need to face the unimaginable challenges ahead when it came to creating my own family.

Do you read yourself and if so, what do you like to read

Funnily enough I’ve always enjoyed tales of goodness and positivity coming out of difficult or challenging circumstances. The God of Small Things is an all time favourite. I also like reading stories that make me cry because invariably they make me think and look for the reasons for the tears which is where you so often find meaning. Tuesdays with Morrie is a good example.

What are you currently reading

I’m embarrassed to say I haven’t read a book since before I started writing my own. There was no spare time during the writing and there has been even less time since its release as I’ve been promoting it. The last book I read was Wild by Cheryl Strayed suggested to me by my publisher as a great example of how to write a memoir. I enjoyed it immensely and obviously it’s been a huge success.

What are the best things that have happened as a result of writing your book

The best thing that has happened has been the feedback from other people who have sent me messages from literally all over the world from India to Africa to the Americas and Asia, telling me how much my story has moved them, made them appreciate their lives and families all the more and given them hope, especially women who want to become mums but are still childless by chance and considering their options to create a family outside the box. I have replied to each and every message and each of them makes me believe that it was the right thing to do putting myself out there so personally by telling my life story.

The other thing has been getting the chance to read my story as a ‘reader’. Of course I still think of ways I could have bettered it but I sat on a plane to Japan and read my story for the first time. Whereas before it had just been the life I had lived, but in reading I understood why others see it as an exceptional life and exclaim my strength in not only surviving but being happy. These are the good things. The rest is just media!

Family of seven.

There has been a lot written about the ‘happy ending’ to your story – you are now married, mum to a happy and healthy daughter and part of a large family but how would you describe your life right now

I like to think of this phase of my life since meeting Scott as a happy new beginning rather than a happy ending as the media have positioned it. It’s the start of a family life I never thought I’d have. There was a time when I didn’t think marriage and family were possible for me and my wildest dreams never envisaged me as a stepmother to four other kids. Now we are a big family in a busy and chaotic household of seven plus the boys’ girlfriends and I couldn’t be happier. But, I am taking nothing for granted and still living in the moment as my sons taught me to and appreciating each and every happy day.

How I Met Your Father book cover.

Aminah’s memoir can be purchased at
Book Depository, iBooks or Amazon for the Kindle version.

Australian Story: view the documentary that started it all


This article first appeared in the Information Point newsletter in 2016 when Toni Abram who is diagnosed with dominant centronuclear myopathy wrote about taking part in a Spaceathlon Challenge to raise funds for the Neuromuscular Centre, where she attends for physiotheraphy treatment with her father Mike.

Toni and Mike

During May my dad and I took part in a Spaceathlon Challenge to raise funds for the Neuromuscular Centre (NMC) in Cheshire, where we both attend for physiotherapy treatment. The NMC is a national Centre of Excellence for adults with muscular dystrophy, providing ongoing, specialist physiotherapy, employment and training, advice and support to 1,000 individuals (and their friends, families, and carers) affected by neuromuscular conditions.

The centre is also a charity and 60% of the running costs of the centre come from fundraising but its services are free for its service users, many of whom travel from across the country and further afield to access the knowledge and expertise available.

Neuromuscular conditions affect over 70,000 individuals in the UK and range in severity, onset and presentation. Some conditions are diagnosed at birth, while others do not become apparent until later in life, as was the case with dad and me. However, all conditions present challenges and affect independence, mobility and quality of life and all share one unifying feature, muscle weakness, which is often progressive and can lead to changes in the ability to walk, climb stairs, washing and dressing. Individuals affected by neuromuscular conditions are often less mobile, less able to access active exercise and therefore more at risk of secondary health problems in the future.

You can learn more about the NMC and neuromuscular conditions in the short film below.

Toni and Mike

Dad and I began attending the NMC shortly after getting our diagnosis of centronuclear myopathy and are incredibly fortunate that it is almost on our doorstep. Finding the NMC was a godsend, for on getting our diagnosis, we were told there were very few others in the world with the illness, that there was no treatment and that no long term prognosis could be provided. In addition no counselling was given to help us come to terms with what our futures held and to enable us to deal with our diagnosis emotionally.

For a while previously, I had attended a physiotherapy clinic at my local hospital – the physio who was not trained to understand muscle diseases would spend considerable time twisting and moulding my body and placing my feet and arms in a particular way, only for me to immediately ‘flop’ the moment she left me to stand alone because my muscles are simply not strong enough and therefore totally resisted this regularly prescribed type of physio treatment. Attending for physio at the NMC however is a different matter entirely. My treatment is designed for me and rather than trying to make my body work normally or trying to cure me, the focus is on maintaining the movement and flexibility that I currently have for as long as possible. My physio’s understand muscle disease and always take the time to ask about recurring problems or whether there are any new issues since my last visit and are able to offer a number of ‘on site’ solutions for regular or one off aches and pains, such as an infra red heat lamp, ultrasound and ‘wellies’ which help with circulation problems.

Attending the centre has also connected my father and I to others with muscle diseases and although they have different conditions to us (there are 60 to 70 types of MD), they understand what we are going through, as we all experience similar physical problems. The NMC also provides other types of support, for instance they were able to advise me on an Access to Work scheme and provide me with a letter of support to give to my employer and I know that should I require any other assistance in the future, they would be there for me.

Without the NMC my father and I would still be living with the knowledge that we have a chronic health condition but feeling very isolated and not knowing where to turn for help and support and although we are both aware that our condition is progressing and that there is no cure for us, attending the NMC has enabled us to re-gain some control in the battle against our disease. We are grateful to have found a sort of home inside the walls of the NMC and taking part in the Spaceathlon, is an opportunity for dad and I to give something back by taking part in a fundraising activity for the centre. Also to raise awareness of the work of the centre and the benefits of exercise for people with muscle conditions, as well as improving our own fitness.

The challenge

Inspired by British Astronaut Tim Peake, the effects of zero gravity during space flights which cause astronauts to experience loss of muscle tissue and bone density and the Space to Earth Challenge set by Tim to get fit with him, the aim of the Spaceathlon is simple, to encourage the whole NMC community to contribute to a cumulative distance of 460km (the maximum distance between the earth and the ISS) by taking part in physical activities and to raise funds for the centre in the process. Based on a triathlon, participants could walk using a cross trainer, cycle using pedals or assisted arm pedals, swim in the hydro pool or row using the rowing machine.

Research indicates that exercise (at an appropriate intensity and frequency) is beneficial for individuals with muscle conditions, not only in providing a stimulus to maintain muscle strength but also improving whole body fitness and reducing soft tissue tightness and pain. So the NMC has asked their clients to think about their own levels of activity and to set themselves a challenge. This could take the form of a specific time or distance or simply doing a little more active exercise than usual (as is the case with dad and I), with some clients aiming to cover a half marathon distance on the centres bespoke, wheelchair accessible arm and leg pedals, swimming the length of the ISS in the hydrotherapy pool or rowing to the stratosphere. While some are incorporating three elements to their Spaceathlon challenge, linking it with the triathlon theme.

The science bit

So how does Tim Peake and the Space to Earth Challenge relate to neuromuscular conditions? The progressive nature of muscle conditions is similar to observations made of astronauts in space. After five months in orbit above the earth an astronaut would typically lose as much as 40% of muscle and 12% of bone mass. Therefore astronauts have to undergo daily rigorous exercise to try to help counteract the loss of bone and muscle fibre, together with other risks such as shrinking legs due to fluid redistribution, deterioration of weight baring bonus and muscles and forgetting how to walk, that come with living in microgravity. And just like like an astronaut, if people with neuromuscular conditions don’t exercise, their muscles will waste away faster still, so some physical activity, despite what people might think, is really important. It is not at all easy but helps with cardiorespiratory fitness, energy efficiency, weight management and muscle performance – exercising muscles maintains flexibility, length and strength and helps maintain better function for longer.

Similar to a thermostat that only maintains a temperature when it is needed, bodies only maintain or build muscle when muscles are used repeatly. This is why body builders are able to gain muscle bulk by repeated weight lifting and also the reason why astronauts need to do so much exercise when in space – where the lack of gravity reduces the stimulation the body would normally receive from physical activity, taking away muscle tissue and bone it believes to be unnecessary. This mechanism is reproduced in neuromuscular conditions, where reduced activity and reliance upon powered mobility aids such as wheelchairs, leads to a reduction in muscle mass.

And finally

35 participants took part in the Spaceathlon raising around £4,000. The Space Crew covered the 460km to the International Space Station and made it back to earth too, a total of 920km but the actual total reached was 1,000+ km and all this without adding on the distances covered by people who did their challenge outside of the centre (which included three triathlons, 1,000 lengths of swimming and walking.

Donate and get involved

If after reading this, you would like to make a donation or get involved with the work of the centre, you can do so below.

* Make a donation
* Get involved

Further information

* Exercising with a muscle condition
* What happens to muscles in space
* Space to Earth Challenge


Spaceathlon flyer  space-flyer-3

Titin mutations cause centronuclear myopathy

This story first appeared in the Information Point newsletter Our World in 2013, when Sarah Foye, Lindsay Swanson, MS, CGC and Elizabeth Torosian told the The Information Point about the discovery that mutations in the Titin (TTN) gene can cause centronuclear myopathy.

As you may know, the congenital myopathies are a group of inherited disorders (passed down from parent to child) that affect the structure of muscles. The class of myopathies known as centronuclear myopathy (CNM) have historically been named due to the muscle cells appearance under the microscope. The nuclei of muscle cells affected by CNM tend to be found in the center of the cell, unlike in healthy muscles where the nucleus is found on the edge of the cell. These internalized nuclei are what give CNM it’s name, but there are several genes known to cause various forms of CNM. These genes are MTM1, DNM2, RYR1, BIN1 and TTN however some genes still remain unknown.

New gene discoveries are taking place as muscle disorder researchers learn more about CNM and more technologies become available. One new technology being utilized in the research lab of Dr Alan Beggs includes whole exome sequencing (WES) and whole genome sequencing (WGS). These new technologies, which can be less expensive than traditional genetic sequencing, allow researchers to look at larger chunks of the human genetic code.

Using this technology, the Beggs Lab, along with a group of collaborators, discovered that mutations in the Titin (TTN) gene can cause CNM. Titin, the largest known protein in the human body, is coded by the TTN gene. It is a structural protein that acts as a molecular spring within the muscle cell, as seen in the drawing to the right. Although Titin has long been known to be a structural protein within the muscle cell, examination of the gene TTN has been limited due to it’s gigantic size. However, the use of new genetic testing methods like WES and WGS have allowed researchers to understand more about Titin and the TTN gene. You can read more about this in the article below.

Beggs et al, used the new genetic testing methods to screen a group of subjects who were diagnosed with CNM by muscle biopsy but tested negative for mutations in all genes known to cause CNM. Through this process, they identified that TTN mutations were likely the genetic cause in five individuals with CNM. You can read more about this in the article below:

However, there still remains a large category of people diagnosed with CNM whose genetic cause remains unknown. With new gene discoveries and new technologies, it can be expected that people can jump from the ‘unknown’ category into a category with a known gene. New clinical testing can help ease the diagnosis by testing for many genes simultaneously. The University of Chicago Genetic Services Laboratories is now offering a state of the art test in which multiple congenital myopathy genes can all be tested at once. Known as next generation sequence genetic testing. This type of testing is faster and cheaper than prior testing methods. This panel includes the TTN gene. If you or a family member have been diagnosed with MTM or CNM but never had a genetic mutation identified or confirmed through a clinical lab, please consider discussing this with your doctor or a genetic counselor.

One final point to note is that TTN mutations are known to cause a heart problem known as adult onset dilated cardiomyopathy. This can have important clinical implications for people who may have CNM caused by a TTN mutation and may be another important reason to have the genetic testing done. Additionally, any person with heart problems and a congenital myopathy may strongly consider TTN as a possibly cause.

International collaboration

Since 2011 the Myotubular Trust has been funding a grant to Dr Jocelyn Laporte at IGBMC in France to use next generation gene sequencing technology to find some of the other genes that cause myotubular and centronuclear myopathy. Jocelyn Laporte says ‘The team in Strasbourg is supported by Myotubular Trust to identify genes linked to myotubular and centronuclear myopathies using the novel genome sequencing approach. Due to this support the lab were able to participate to an international collaborative study that culminated in the identification of mutations in Titin in patients presenting with centronuclear myopathy. Titin is the largest protein of the human body and acts as a molecular spring during muscle contraction and relaxation. Other families with centronuclear myopathy that have previously eluded genetic diagnosis may turn out to be linked to this same gene. Researchers can now use this finding to better establish diagnosis and understand how these myopathies occur’.

The discovery of the Titin protein’s role in this condition is a great example of the power of international collaboration between leading neuromuscular research teams. This is really good news for our community

Genetic testing

If you have been diagnosed with myotubular myopathy but have never had your MTM1 mutation identified of confirmed in a clinical laboratory, you may want to consider enrolling in the MTM Genetic Testing study.

For European patients, where the culprit gene has not been identified via genetic testing, retesting can be requested via a clinician, as most diagnostic laboratories in Europe are currently validating these novel sequencing technologies. In Europe, such a request for re-testing must be made via a clinician, rather than directly to a laboratory and testing is free in some countries.