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We have been asked to share this letter from Dr Baranello and Dr Dowling, the prinicipal investigators on the tamoxifen trial for x-linked myotubular myopathy.

In partnership with Great Ormond Street Hospital (GOSH) Charity, we are delighted to announce a new 3 year grant award to Professor Francesco Saverio Tedesco at University College London (UCL).

What are the researchers planning to do?
The research team at UCL will make patient-specific 3D ‘mini-muscles and livers’ in the laboratory using cells called induced pluripotent stem (iPS) cells. iPS cells are made by taking cells from the body, such as skin cells, and genetically ‘reprogramming’ them so that they can be developed into any type of cell in the body. In this project, the cells will have come from patients with XLMTM, so the resulting 3D mini-muscles and livers will be human models of XLMTM.
The researchers will then test different gene therapies in the mini-muscle and liver models and measure what effect they have. For example, they will measure whether there is an increase in the muscle fibre size and/or a reduction in liver side effects. 
 
Why is this research important?
In recent years, it has become clear that some people with X-linked myotubular myopathy (XLMTM) can have problems with their liver. Unfortunately, two clinical trials – one of which was testing gene therapy - were stopped due to unexpected side effects in the liver, which sadly were fatal for four patients on the gene therapy trial. 
 
To better predict potential side effects of treatments in clinical trials, we need preclinical models of XLMTM that are more like humans with the condition. This research project aims to develop human muscle and liver models of XLMTM and then test potential gene therapies in these models. This work will not only be valuable for future preclinical studies testing potential treatments but may also help to give a better understanding of how the XLMTM genetic change can affect how the liver works and responds to stress.
 
Who is doing the research?
Prof Tedesco will be overseeing the research project. He has pioneered the development of mini-muscle models based on human stem cells and is an expert in neuromuscular conditions and muscle regeneration.
 
The research will mainly be carried out by Dr Valentina Maria Lionello, a postdoctoral researcher in Prof Tedesco’s lab. She received her PhD training under Dr Jocelyn Laporte at the University of Strasbourg, France, who is an expert in centronuclear myopathies including XLMTM. Dr Lionello’s PhD was partly funded by the Myotubular Trust, so we are truly delighted to be supporting her once again with this important research.

Thank you!
This grant is only possible because of you, our supporters.
Since founding in 2006, every penny you've raised has been invested in research as we have succeeded year on year to raise our running costs separately. This means that each and every donation makes a difference to our scientific understanding, and to the development of potential therapy routes for our group of conditions.

Dear Melanie,

In earlier work by Dr Jim Dowling at Sick Kids, Toronto, and funded by Myotubular Trust grants, it was discovered that tamoxifen, the well known breast cancer drug, could significantly improve the symptoms of x-linked myotubular myopathy. In 2018 we were able to make another 3 year grant of £216,000 to Dr Dowling to pursue this promising work.

The second avenue of research was to use broad based drug screening to find new potential therapies. To do this, we used our novel zebrafish model of the disease. We performed a screen of 1500 “clinically ready” drugs, testing to see which drugs can improve the changes seen in our zebrafish model. We found 4 “hits”; i.e. drugs that reproducibly improved the fish. We focused on one of these hits, an anti-seizure drug commonly used in clinical practice. We tested this drug plus another that is biosimiliar. Lastly, we performed additional work to identify how the drug is working, and through this found a new pathway regulated by MTM1 and abnormal in models of XLMTM and in patients. We will continue to study this novel pathway, and work to translate this drug target to patients."
Dr Jim Dowling, 2021

Great Ormond Street Hospital Charity (GOSH) and Sparks have announced a national funding call in child health research. Under this funding call up to £2M is available to support project grants from researchers across the UK. This year they have again partnered with a small number of rare disease charities, and we are delighted that again they have chosen to work with Myotubular Trust - with a request for applications that further the search for a cure or treatment for any of the genetic forms of myotubular and centronuclear myopathy.

We are proud to be part of a partnership with these two organisations who have done so much to further the health of children, and we thank all our donors and fundraisers who make it possible for us to be part of such a partnership.

Essentially, mTORC1 is a master regulator of muscle growth – from early steps of muscle differentiation in the womb, to the work of muscles in adult life. Dr Hnia’s laboratory has been investigating this chemical pathway in x-linked myotubular myopathy (XLMTM) and they have shown that mTORC1 is ‘overactivated’ when XLMTM is present. A two year grant of £82,000 from the Myotubular Trust will assist them in furthering this work.

What makes this a very exciting project is that, through other diseases, there are a number of drugs already licensed that regulate mTORC1 levels. The ultimate goal of this research is to identify if mTORC1 inhibition could lead to a new strategy for treatment in humans with x linked myotubular myopathy. Read more here

Funding

These grants from Myotubular Trust are only possible because of the fundraising of our families and supporters. Since founding in 2006, 100% of your fundraising goes into promising research projects such as Dr Hnia's 2020 grant.

Myotubular Trust has raised all administration costs separately, by applying to other charities, foundations, and specific sponsors. This enables every single penny you donate to make a difference to our scientific understanding, and the development of potential therapy routes for our group of conditions. Thank you! 

If, like us, you are having a lockdown clear out and have any unwanted items, they can be sold on eBay to help raise funds for the Myotubular Trust.  You decide exactly what percentage of your final selling price you’d like to donate and what percentage you’d like for yourself.  You can donate anything from 10-100% of the final selling price with a minimum donation of £1 per item.  
If you know of any other no-cost ways in which we can continue to raise funds during this time please do let us know -  we would really love to hear from you.

We hope that our Calendar of Events and previous fundraising stories will help to inspire you, and give you some ideas.  There are no rules when it comes to arranging your own event – it can be as simple as a sponsored silence, as extravagant as a fundraising ball, and on as large or as small a scale as you like,  Every penny you raise will be used to fund further research.  More information on designing your own event can be found here.

We hope you enjoy being creative and If you do need some help or ideas, please don’t hesitate to contact us.  We would love to hear from you!

• This first study is primarily concerned with safety and tolerability of the drug, as well as the best way to administer the drug;
• The trial will be conducted in patients aged 16 and over;
• Studies in younger patients are planned later in the development and will be based on data emerging from this first study.