Each nemaline myopathy focused research publication listed here is a testament to the power of collaboration between AFBS and researchers who share our mission to drive progress toward treatments for nemaline myopathy. These scientific papers represent the cutting-edge discoveries and collaborations made possible through AFBS’s support, underlining our commitment to driving progress in nemaline myopathy research, ultimately striving for treatments and improved lives.

Aberrations in Energetic Metabolism and Stress-Related Pathways Contribute to Pathophysiology in the Neb Conditional Knockout Mouse Model of Nemaline Myopathy
October 2023, Michael W Lawlor et al.
In a study using a mouse model of nemaline myopathy, researchers found that problems with energy metabolism and stress-related pathways play a role in the development of the condition. This insight may pave the way for new approaches to understand and potentially treat nemaline myopathy.

Different Mouse Models of Nemaline Myopathy Harboring ACTA1 Mutations Display Differing Abnormalities Related to Mitochondrial Biology
October 2023, Michael W Lawlor et al.
Various mouse models of nemaline myopathy, which have specific genetic mutations, exhibit different issues related to how their cells use energy from mitochondria. This research sheds light on the complex nature of the disease and its connection to mitochondrial function in these models.

NRAP reduction rescues sarcomere defects in nebulin-related nemaline myopathy
September 2023, Vandana A. Gupta et al.
This research shows that genetic ablation of nrap in nebulin deficiency restored sarcomeric disorganization, reduced protein aggregates and improved skeletal muscle function in zebrafish. The findings suggest that Nrap is a disease modifier that affects skeletal muscle structure and function in NM; thus, therapeutic targeting of Nrap in nebulin-related NM and related diseases may be beneficial for patients.

Inspiratory Muscle Training in Nemaline Myopathy
September 2023, Jonne Doorduin et al.
This study explores the benefits of a breathing exercise program for individuals with nemaline myopathy, a rare muscle disorder. The research investigates how training the muscles used for breathing can improve respiratory function and overall well-being in these individuals

Dynamic regulation of inter-organelle communication by ubiquitylation controls skeletal muscle development and disease onset
July 22, 2022 
Vandana A Gupta et al.
This important study utilizes a model organism, zebrafish, to explore the roles of KLHL40, a component of the ubiquitin-proteasome system (UPS), in the development of skeletal muscle disease. The compelling data on proteome remodeling and UPS-regulation of biosynthetic secretion make this work interesting to biologists who study the UPS, muscle development and intracellular traffic.

NEB mutations disrupt the super-relaxed state of myosin and remodel the muscle metabolic proteome in nemaline myopathy
December 2022, Julien Ochala et al.
Mutations in the NEB gene cause changes in muscle function and metabolism in nemaline myopathy by affecting a relaxed state of muscle fibers. This research sheds light on how these genetic changes impact muscle health.

Generation of two isogenic induced pluripotent stem cell lines from a 1-month-old nemaline myopathy patient harbouring a homozygous recessive c.121C > T (p.Arg39Ter) variant in the ACTA1 gene
August 2022, Joshua S. Clayton et al.
Scientists have successfully created two identical stem cell lines from a young patient with nemaline myopathy, who had a specific genetic mutation in the ACTA1 gene. This achievement paves the way for future research to better understand and potentially treat this rare muscle disorder.

Generation of an induced pluripotent stem cell line from a 3-month-old nemaline myopathy patient with a heterozygous dominant c.515C > A (p.Ala172Glu) variant in the ACTA1 gene
August 2022, Rhonda L. Taylor et al.
Researchers have successfully created a versatile stem cell line from a young patient with nemaline myopathy, who had a specific genetic mutation in the ACTA1 gene. This breakthrough opens doors to future investigations and potential therapies for this rare muscle disorder.

Removal of MuRF1 Increases Muscle Mass in Nemaline Myopathy Models, but Does Not Provide Functional Benefits.
August 2022, Henk Granzier et al.
Eliminating MuRF1, a protein, leads to increased muscle mass in nemaline myopathy models, but it doesn’t necessarily improve muscle function. This research suggests that while muscle size can be enhanced, other factors might be more critical for improving muscle performance in this condition.

Generation of two isogenic induced pluripotent stem cell lines from a 1-month-old nemaline myopathy patient harbouring a homozygous recessive
April 2022, Joshua S. Clayton et al.
This research explains the iPSC lines demonstrated typical morphology, expressed pluripotency markers, exhibited trilineage differentiation potential and displayed a normal karyotype. These isogenic lines represent a potential resource to investigate and model recessive ACTA1 disease in a human context.

NEB mutations disrupt the super-relaxed state of myosin and remodel the muscle metabolic proteome in nemaline myopathy
2022, Julien Ochala et al.
The aim of the study was to define the exact molecular and cellular cascade of events that would lead to potential changes in muscle energetics in NEB-NM. The findings explain some of the hitherto obscure hallmarks of NM, including the appearance of abnormal energy proteins and suggest potential beneficial effects of drugs targeting myosin activity/conformations for NEB-NM.

Recent advances in nemaline myopathy
July 2021, Jenni Laitila, Carina Wallgren-Pettersson
This research suggests a renewed clinical classification to replace the original one, summarizes what is known about the pathogenesis from mutations in each causative gene to the forms of nemaline myopathy described to date, and provides perspectives on pathogenetic mechanisms possibly open to therapeutic modalities.

A cross-sectional study of nemaline myopathy supplementary figures
January 2021, James J. Dowling, MD, PhD et al.
Fifty-seven individuals with NM were recruited at two family workshops, including 16 examined at both time points. Subjects were evaluated by clinical history and physical examination. In all, the group presented a comprehensive cross-sectional study of NM. The data identifies significant disabilities and supports a relatively stable disease course. They identified a need for further diagnostic investigation for the genetically unresolved group.

Triggering typical nemaline myopathy with compound heterozygousnebulin mutations reveals myofilament structural changes as pathomechanism 
August 2020, Henk Granzier et al.
In this study, a mouse model was engineered to replicate typical nemaline myopathy (NM) with specific genetic mutations, resulting in stunted growth and muscle weakness. Examination of these mice revealed structural changes in muscle fibers, including twisted actin filaments, altered behavior of proteins like tropomyosin and troponin, and increased spacing between muscle fibers, shedding light on potential therapeutic targets for nebulin-based typical NM.

Nebulin nemaline myopathy recapitulated in a compound heterozygous mouse model with both a missense and a nonsense mutation in Neb
February 2020, Jenni M. Laitila et al.
No existing murine models possess compound heterozygous Neb mutations that reflect the genotype and resulting phenotype present in most patients. This research aimed to develop a murine model that more closely matched the underlying genetics of NEB-NM, which could assist elucidation of the pathogenetic mechanisms underlying the disease.The moderate phenotype also makes this an appropriate model for studying NEB-NM pathogenesis, and could potentially be suitable for testing therapeutic applications.

Expressing a Z-disk nebulin fragment in nebulin-deficient mouse muscle: effects on muscle structure and function 
January 2020, Frank Li et al.
This research studied whether sarcomeric structure and function can be improved by introducing nebulin’s Z-disk region into a nebulin-deficient mouse model (Neb cKO) through adeno-associated viral (AAV) vector therapy. Following this treatment, the structural and functional characteristics of both vehicle-treated and AAV-treated Neb cKO and control muscles were studied.

Omecamtiv mecarbil lowers the contractile deficit in a mouse model of nebulin-based nemaline myopathy
November 2019, Henk Granzier et al.
For this research, a new medication called Omecamtiv mecarbil shows promise in improving muscle function in a specific mouse model of a rare muscle disorder. This research offers hope for potential treatments to enhance muscle strength in people with similar conditions.

Failure to identify modifiers of NEBULIN-related nemaline myopathy in two pre-clinical models of the disease
September 2019, James J. Dowling et al.
In two pre-clinical models, researchers couldn’t find factors that make NEBULIN-related nemaline myopathy better or worse.

Dysregulation of NRAP degradation by KLHL41 contributes to pathophysiology in nemaline myopathy
April 2019, Vandana A Gupta et al.
In nemaline myopathy, there is a problem with how a protein called NRAP is broken down, and this contributes to the disease’s development. Researchers have found this dysregulation as a potential key factor in understanding the condition.

Myostatin Inhibition Using ActRIIB-mFc Does Not Produce Weight Gain or Strength in the Nebulin Conditional KO Mouse
December 2018, Michael W Lawlor, MD, PhD et al.
Using a substance called ActRIIB-mFc to block myostatin did not result in weight gain or increased strength in a specific mouse model, despite hopes for its potential benefits. This research highlights the need to explore alternative approaches for addressing muscle-related issues.

TNNT1 nemaline myopathy: natural history and therapeutic frontier
September 2018, Kevin A Strauss et al.
This study delves into the natural course of TNNT1 nemaline myopathy and explores new possibilities for potential treatments. It aims to better understand this condition and discover novel ways to improve the lives of affected individuals.