Early Career member Dr. Jean-Philippe Leduc-Gaudet identifies gene involved in regulating autophagy and skeletal muscle integrity

We are excited to share the publication of a ground-breaking new study from NMD4C early career member Dr. Jean-Philippe Leduc-Gaudet in the journal Nature Communications. NMD4C investigators Drs. Elise Duchesne and Hanns Lochmüller are also co-authors on the study “MYTHO is a novel regulator of skeletal muscle autophagy and integrity“, which identifies a previously unknown gene involved in regulating autophagy and skeletal muscle integrity.

 

Mytho gene identified as regulator of autophagy and skeletal muscle health

Autophagy is a cellular process that plays a critical role in maintaining cellular homoeostasis by eliminating damaged or unnecessary components, such as misfolded proteins and organelles, and is a critical process in the regulation of muscle mass, function, and integrity, but the molecular mechanisms behind it are complex and not yet fully understood. Through a series of innovative experiments and analyses, the team of scientists was able to identify and characterize a novel FoxO-dependent gene, d230025d16rik, which they named Mytho (Macroautophagy and YouTH Optimizer), as a regulator of autophagy and skeletal muscle integrity in vivo.

 

This discovery is a significant breakthrough in our understanding of the regulation of autophagy and skeletal muscle integrity. The gene we have identified plays a crucial role in skeletal muscle atrophy and could provide a new target for the development of therapies for muscle-related diseases.” Explain lead authors Drs. Jean-Philippe Leduc-Gaudet and Anais Franco-Romero.

 

In this study, the team of scientists found that Mytho is significantly up-regulated in various mouse models of skeletal muscle atrophy. The researchers then showed that short-term depletion of MYTHO in mice attenuates muscle atrophy caused by fasting, denervation, cancer cachexia, and sepsis.

 

In a series of experiments, researchers also found that prolonged Mytho depletion is associated with severe myopathic features, including impaired autophagy, muscle weakness, myofiber degeneration, and extensive ultrastructural defects. The researchers then found that inhibition of the mTORC1 signaling pathway in mice using rapamycin treatment attenuates the myopathic phenotype triggered by prolonged MYTHO knockdown. In other experiments, the researchers found that human patients diagnosed with myotonic dystrophy type 1 (DM1) display reduced Mytho expression, activation of the mTORC1 signaling pathway and impaired autophagy. This suggests that dysregulation of Mytho expression may also contribute to human muscular diseases.

 

The study, conducted by a team of local and international scientists led by Drs. Sabah Hussain (IR-MUHC), Gilles Gouspillou (UQAM), and Marco Sandri (UPadova), was funded by the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC), the Fonds de recherche du Québec-Santé (FRQS) and supported by the AFM-Téléthon.

 

The publication can be found at the following link: https://www.nature.com/articles/s41467-023-36817-1?fbclid=IwAR0QMdRnjf_6IbAcvOUTvCryhmqa6k-Efu5uK4nBFG2DiZEfrxZUcSddK7M

 

JP LG mytho study4x3

Read next...

Defeat Duchenne Canada logo.

Defeat Duchenne Canada launches 2023 Research Grant Program

DDC invites research proposals for their 2023 research grant program of a translational or clinical nature focused on improving the health and quality of life for individuals living with Duchenne muscular dystrophy.

Oskoui clinical trial graphic_4x3

Investigator Dr. Maryam Oskoui Receives CIHR Grant to Fund Spinal Muscular Atrophy Clinical Trial

NMD4C investigator Dr. Maryam Oskoui was awarded a Canadian Institutes of Health Research Clinical Trials Operating Grant for INFORM SMA as nominated principal applicant.

BIND study poster; graphic of computer and scale in centre, NMD4C logo with MDC and CNDR, OHRI in top right and link to study below.

New CIHR-funded Burden of Inherited Neuromuscular Disease (BIND) Study: Assessing the Indirect Socio-Economic Burden of Inherited Neuromuscular Diseases

The BIND study’s goal is to assess the social and economic burden of Canadians living with neuromuscular disorders by using web-based surveys to assess quality-of-life, healthcare resource use, work productivity, and effect on schooling and careers.

text reading Canadian FSHD registry, with icons in centre of page and CNDR and MDC logos underneath.

Muscular Dystrophy Canada, Canadian Neuromuscular Disease Registry, NMD4C partner to ensure Canadians can access Facioscapulohumeral muscular dystrophy (FSHD) cure(s)

MDC and the CNDR are working together with NMD4C to introduce a patient registry and collect information to build a Canada-wide core dataset for FSHD.

Congratulations to the early career award recipients! Photos of the three recipients, with text reading biomedical researcher of the year, clinical researcher of the year, publication of the year.

NMD4C Announces 2023 Early Career Award Recipients

We are excited to announce the recipients of the inaugural NMD4C Early Career Investigator Awards for 2023! This annual award program introduces three new awards, celebrating excellence and contribution to the neuromuscular field by early career investigators across both clinical and basic science streams.

NMD4C 2022 year in review poster

2022 NMD4C Year in Review

The NMD4C would like to reflect on all the inspiring progress the network has made towards the network’s goals in 2022. This year in review outlines a collection of achievements from the network over the past year.