You can now watch the TAM4MTM Webinar recording

On 3rd December 2024, the Myotubular Trust hosted a webinar following the news that the TAM4MTM trial had been stopped due to the impact the drug tamoxifen had on the liver function of two trial participants. The webinar not only provided an opportunity for our community of patients and their families to ask questions about the TAM4MTM trial, but also to find out what new work is being done to investigate the liver more closely in patients with xlmtm (X-linked myotubular myopathy). The full recording of this webinar can be found below (or by this YouTube link). Please scroll down to find a full transcript of the webinar and the Q&As, together with an outline background on the TAM4MTM trial. You can also read the letter to the patient community here about the stopping of the trial.

Background on the TAM4MTM trial

It was believed that the drug, tamoxifen was promising as a potential therapy for patients with xlmtm (X-linked myotubular myopathy), based on some of the pre clinical work* by Dr James Dowling at Sick Kids Hospital Toronto, as well as from independent research* in the laboratory of Dr Oliver Dorchies. It is a drug with quite a bit of experience already in patients because tamoxifen is already being used as a chemotherapeutic drug for treating oestrogen responsive breast cancer. It was based on this, that Dr Dowling’s research laboratory considered doing a human clinical trial. This subsequently took place in both Canada and UK, to evaluate the effectiveness and safety of repurposing tamoxifen to help treat patients with xlmtm – and was called TAM4MTM, or tamoxifen for myotubular myopathy. Please watch the webinar, or read the full transcript for more background information about how the trial was organised to meet its objectives, and why it needed to be stopped. Data analysis on the seven clinical trial participants is still ongoing and is expected to be available in Spring 2025.

Download the Transcript of TAM4MTM Webinar, 3rd December 2024 (pdf).

Download the Questions and answers from the TAM4MTM Webinar (pdf)

Myotubular Trust’s investment in XLMTM and the liver is still ongoing

Due to the generosity of all of those who fundraise for us, the Myotubular Trust has been able to respond quickly to clinical developments over the last few years and invest in three preclinical research grants studying the liver in XLMTM:

• In 2022, we awarded a grant of £135,000 to Dr Ana Buj Bello to assess what happens to liver cells after gene therapy treatment so better gene therapies can be developed.
• In 2023, in partnership with Muscular Dystrophy UK, we awarded a grant of £300,000 to Prof Jim Dowling to study mouse and human liver cell models of XLMTM to see how the liver works and responds to stress.
• In 2024, in partnership with Great Ormond Street Children’s Charity, we awarded a grant of £249,000 to Prof Francesco Saverio Tedesco to develop 3D ‘mini-muscles and livers’ with the XLMTM genetic change that can be used as preclinical models to test potential treatments.

The important role the MTM & CNM Patient Registry is playing to investigate liver function

The MTM & CNM Patient Registry is also actively collecting liver data through the Liver Health Questionnaire. This was developed by the MTM-CNM Liver Collaborative with help from a broad range of community experts. Data is welcomed from all patients in the community, whether or not liver symptoms have been experienced. Please consider joining the Registry, or updating your registration.

The MTM-CNM Liver Collaborative has also been instrumental in creating the leaflet, “Liver Considerations for Myotubular and Centronuclear Myopathy”, for patients to share with their medical teams.

It is our hope that understanding the role of the liver in XLMTM will mean safer and potentially more successful clinical trials in future, and improved standards of care in the present.