We are delighted to share the news that our second grant award of 2020 goes to Dr Karim Hnia at the world renowned French research institute, INSERM, investigating a very promising question – Is the mTORC1 pathway a route to treatment in x-linked myotubular myopathy?
The laboratory of Dr Karim Hnia at INSERM in Toulouse have been investigating this chemical pathway in x-linked myotubular myopathy (XLMTM) and a two year grant of £82,000 from the Myotubular Trust will assist them in furthering this work.
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. The work of Dr Hnia’s laboratory has shown that mTORC1 is ‘overactivated’ when XLMTM is present. What makes this a very exciting project is that through other diseases there are a number of drugs already licensed to regulate mTORC1 levels.
Background
MTM1, the gene mutated in x-linked myotubular myopathy, is responsible for an enzyme that converts specific lipids in the body called phosphoinositides (PIs). The current knowledge about the role of these specialised lipids to cause x-linked myotubular myopathy remains very limited.
However, research over the last few years has shown that they are involved in important processes that both create and renew muscle protein, and in the movement of molecules in and out of muscle cells.
The promising specific discovery made by Dr Hnia’s team is that one of the particular muscle related processes affected by mtm1 is mTORC1 – a master regulator of muscle growth. It would appear that there is an interaction between MTM1 and the lipids that myotubularin should normally work on, that has a negative effect on mTORC1 and essentially causes this pathway in the body to be overactivated. Dr Hnia’s team used mTORC1 inhibition on XLMTM in laboratory experiments, and observed a significant beneficial effect on muscle symptoms and lifespan.
In this project funded by Myotubular Trust, Dr Hnia and his team aim to:-
- Dissect the molecular link between MTM1, the lipids MTM1 normally works on, and discover how they link to mTORC1 activation
- Extend and confirm the physiological benefit of mTORC1 inhibition in XLMTM by testing different drug concentrations in the laboratory.
The ultimate goal of this project is to identify if mTORC1 inhibition could lead to a new strategy for treatment in humans with x linked myotubular myopathy.
Interestingly, mTORC1 has already been proven to be druggable in humans (ie treatable with drugs), and indeed several inhibitors for this already exist (the FDA approved Rapamycin and Rapalog) to inhibit this pathway. They are also currently being tested in many other diseases such as cancers, metabolic diseases and neurological disorders.
Multiple scientific routes to treatment until there are definite treatments for myotubular and centronuclear myopathy
As with all conditions, no one treatment will work for everyone. Therefore it was a founding principle of Myotubular Trust to fund a range of research grants that have the potential to open up as many scientific avenues as possible, until there are treatments in place for all those with myotubular and centronuclear myopathy. Other research grants made by the Trust in the past that are now in human clinical trial, have begun with a project like this. We are delighted to be funding such promising work.
Funding
The grant for this project is 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 its core administration costs separately, by applying to other charities, foundations, and specific sponsors. This enables every single penny that you donate to make a difference to our scientific understanding, and the development of potential therapy routes for our group of conditions. Thank you!
Glossary
Lipids are present in every cell of the human body and are the main part of the membrane of our body’s cells.The body uses lipids as an energy store; as insulation; and to make cell membranes.
Druggable, something that is treatable with drugs.
Physiological, relating to how a bodily part functions.
