1. Global FKRP Patient Registry

    • Dr. Volker Straub at Newcastle upon Tyne University in Newcastle, UK
    • Since 2012

    • Description

      This grant pays for the coordinator of the registry. The registry is part of Treat-NMD, a network with the mission of ensuring that the most promising new neuromuscular therapies reach patients as quickly as possible.

    • Outcome

      As of April 2017, 527 patients from 35 countries had registered since 2011. The proportion of patients with a genetically confirmed diagnosis is 45%.

    • Articles:

      1. Natural History, Trial Readiness and Gene Discovery: Advances in Patient Registries for Neuromuscular Disease. Thompson R, Robertson A, Lochmüller H. Adv Exp Med Biol. 2017 1031:97-124.

  2. Patient Sequencing Project

    • Dr. Madhuri Hegde at the Emory Genetics Laboratory in Atlanta, GA
    • Since 2012

    • Description

      The LGMD2i Research Fund has a dedicated account with the Emory Genetics Laboratory to fund the genetic testing of patients that have a high probability of LGMD2I based on clinical symptoms and family history.

  3. The Rare Disease Awareness Project or MYO-SEQ Project: Application of next generation sequencing technologies to a large cohort of patients affected by unexplained limb-girdle muscular weakness

    • Dr. Volker Straub at the Newcastle Upon Tyne University in Newcastle Upon Tyne, UK
    • 2014-2016; 2017-2019

    • Description

      The goal of the project is to provide centralized genetic diagnosis at a global scale. Individuals with elevated serum CK activity in combination with unexplained limb-girdle muscle weakness were selected for the study; biological samples were prepared and sent to the project team in Newcastle Upon Tyne, UK. DNA was extracted and sent to the Broad Institute (MIT, Cambridge MA USA) for whole exome sequencing.

    • Outcome

      The first 1,000 DNA samples from 41 centers (mainly in Europe) have been sequenced. Of the 1,000 patients, 48.5% had likely causal mutations. Eight out of 1,000 were found to have a mutation in FKRP and were diagnosed with LGMD2I.

    • Articles:

      1. Identification of GAA variants through whole exome sequencing targeted to a cohort of 606 patients with unexplained limb-girdle muscle weakness. Johnson K, Töpf A, Bertoli M et al. 2017 Orphanet Journal of Rare Diseases 12:173-184.
      2. Limb girdle muscular dystrophy due to mutations in POMT2. Østergaard ST, Johnson K, Stojkovic T et al. J Neurol Neurosurg Psychiatry. 2017 88(11):
      3. Novel recessive TTN founder variant is a common cause of distal myopathy in the Serbian population. Peric S, Nikodinovic Glumac J, Töpf A et al. European Journal of Human Genetics 2017 25:572–581.
      4. Homozygous DPM3 mutation in a patient with alpha-dystroglycan-related limb girdle muscular dystrophy. Van den Bergh PYK, Sznajer Y, Van Parys V, et al. Neuromuscular Disorders. 2017 27(11):1043–1046.

  4. Dystroglycanopathies: Patient and Family Conference

    • Dr. Katherine Mathews at the University of Iowa, Carver College of Medicine in Iowa City, IA
    • Since 2012

    • Description

      The “Patient and Family Conference” provides an opportunity for individuals with a dystroglycanopathy (which includes LGMD2I) and their families to receive up to date information about research and clinical developments, and about various issues related to living with dystrophy including public policy, reimbursement, psychology, etc. It also helps individuals with a dystroglycanopathy to meet other people with a similar diagnosis. Importantly, it facilitates the enrollment in the longest running natural history study in individuals with LGMD2I.

  5. Wellness and Quality of Life Survey on Patients with LGMD2I

    • Dr. Masa Sasagawa at Bastyr University in Seattle, WA
    • Since 2017

    • Description

      The goals of this project are to gather information on natural remedies that improve quality of life; analyze, organize, and share the collected information with the LGMD2I community.

  6. Application of Rosetta to Elucidate and Correct FKRP Structure-Function

    • Dr. David Baker at the University of Washington in Seattle, WA
    • Since 2016

    • Description

      The project focuses on computationally designing peptides that will serve as chaperones for mutant forms of FKRP and help fold FKRP so that it is stabilized and its function restored. Chaperones, specific to mutated FKRP, may represent perfect candidates to stop the progression of the disease.

  7. Creation of a mouse model for LGMD2I carrying the P448L mutation

    • The Jackson Laboratory (Bar Harbor, ME)
    • since 2018

    • Description:

      This project will create a mouse model that will be available to all without any restrictions. The rights to the mouse model will be transferred to the Jackson Laboratory for unrestricted distribution.

  8. Investigation of the regulation of FKRP genetic expression

    • Généthon (Evry, France)
    • since 2019

    • Description:

      This project will look at the pattern of the expression of the gene FKRP in the context of the upcoming gene therapy clinical trial in Europe.

  9. Identification of biomarker for FKRP deficiency

    • Généthon (Evry, France)
    • since 2020

    • Description:

      This project will study a new clinical biomarker for LGMD2I in cell and patients’ clinical samples.