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The QUALITY project has been promoted by GFB Odv www.lgmd2e.org. GFB have been dealing with Limb girdle muscular distrophy types 2C/R5-2D/R3-2E/R4 (alfa, beta and gamma sarcoglicanopathy) for 11 years and with the specific scientific research. The president and founder is Beatrice Vola.
As far as 2010 the Limb girdle muscular distrophy (LGMD) was considered a neglected pathology, this means that there was no scientific research on the disease. There were no specific organizations for this disease and clinical studies on patients were very few.
There is currently only one research project for LGMD2E or LGMDR4, based on gene therapy and, at the moment, the first clinical trial on patients is underway, by Sarepta Therapeutics. You can see the trial structure on clinicaltrials.gov at the following link:
There are no registries for LGMD2E or LGMDR4 and other forms of LGMD2D or LGMDR3 and 2C or LGMDR5. Other gene therapy studies on LGMD2D or LGMDR3 and 2C or LGMDR5 are ongoing and very soon clinical trials phase 1 will start. You can find further information on GFB site at the following link:
At present, GFB is the only existing organization dealing with LGMD2E or LGMDR4. For the last 11 years, GFB have been concerned in looking for other families affected by this disease and, nowadays, we are in contact with more than 600 patients, all over the world and belonging to different groups. We strongly believe that together we can do more!
GFB would be to start the Quality project to better define the data collected in the past years.
The QUALITY Project is promoted by GFB organization to structure international patients data collected in past years, study the patients' quality of life and encourage the participation of patients in natural history studies and clinical trials.
In the questionnaire you’ll find questions related to the following subject areas:
The questions will be semi-structured with the prevailing multiple-choice type.
In 2021 the first survey will be administered to the patients affected by LGMD2C-2D-2E (or LGMDR5-LGMDR3-LGMDR4). In the following years, other updating surveys will be administered to study the pathology evolution. We think that we’ll do the survey at least every six months.
There is the possibility to give a funding to the centers that will take part in the project.
All the data will be collected with the patients’ informed consent . The data will be processed for statistical porposes and published on a scientific magazine. In the article, all the associations and the clinical centers taking part to the survey will be mentioned among the authors.
For further information, you can ask for a video call on Zoom with the Quality Project staff.
The project is fully funded by GFB.
GFB attended the
GFB: a project for LGMD quality of life studies
Introduction: Neurofascin, encoded by NFASC, is a transmembrane protein that plays an essential role in nervous system development and node of Ranvier function. Anti-Neurofascin autoantibodies cause a specific type of chronic inflammatory demyelinating polyneuropathy (CIDP) often characterized by cerebellar ataxia and tremor. Recently, homozygous NFASC mutations were recently associated with a neurodevelopmental disorder in two families.
Methods: A combined approach of linkage analysis and whole-exome sequencing was performed to find the genetic cause of early-onset cerebellar ataxia and demyelinating neuropathy in two siblings from a consanguineous Italian family. Functional studies were conducted on neurons from induced pluripotent stem cells (iPSCs) generated from the patients.
Results: Genetic analysis revealed a homozygous p.V1122E mutation in NFASC. This mutation, affecting a highly conserved hydrophobic transmembrane domain residue, led to significant loss of Neurofascin protein in the iPSC-derived neurons of affected siblings.
Conclusions: The identification of NFASC mutations paves the way for genetic research in the developing field of nodopathies, an emerging pathological entity involving the nodes of Ranvier, which are associated for the first time with a hereditary ataxia syndrome with neuropathy.
Keywords: Hereditary Ataxia; NFASC; Neurofascin; Neuropathy; Nodopathy.
GFB Onlus Announces
that Myonexus, a Biotechnology Company in which it has Invested, Signed an Exclusive Partnership with Sarepta Therapeutics for the Advancement of Multiple Gene Therapy Programs Aimed at Treating Distinct Forms of Limb-Girdle Muscular Dystrophies
On May 3rd, 2018 Sarepta Therapeutics, Inc. (NASDAQ:SRPT), a commercial-stage biopharmaceutical company focused on the discovery and development of precision genetic medicine to treat rare neuromuscular diseases, and Myonexus Therapeutics, Inc., a clinical-stage biotechnology company developing transformative gene therapies for various forms of Limb-girdle muscular dystrophies (LGMDs), entered into an exclusive partnership to advance multiple gene therapy programs aimed at treating distinct forms of LGMDs.
GFB Onlus took part at the signing of this agreement between Sarepta and Myonexus, two biotechnology companies headquartered in the United States. GFB Onlus financed most of the pre-clinical work on MYO-101.
Last June, GFB Onlus of Talamona, province of Sondrio, along with four other American organizations, joined Myonexus Therapeutics to support developing gene therapies for LGMD. For years, GFB Onlus has been working to expeditiously bring gene therapy to Europe, and in particular to Milan. Currently, it’s the only European authority participating in the company.
Under the terms of the agreement with Myonexus, Sarepta will make an upfront payment of $60 million and additional development-related milestone payments to purchase an exclusive option to acquire Myonexus at a pre-negotiated, fixed price with sales-related contingent payments. If all development-related milestone payments are met, Sarepta will make payments of up to $45 million over an approximately two-year evaluation period. Sarepta has the option to purchase Myonexus at any time, including upon review of proof-of-concept data.
"We are excited about this agreement, which we did not expect. The involvement of the American biopharmaceutical company - underlines Beatrice Vola, president of GFB Onlus - certainly represents another step forward for the gene therapy project on LGMD2E. We are hopeful that the collaboration between Myonexus and Sarepta will lead to even faster results. We have been striving for years to give our associates concrete feedback and finally we think we are on the right track.”
The program is designed, if successful, to offer first-ever corrective treatments for five distinct forms of LGMD. The most advanced of these programs is MYO-101, which is being developed to treat LGMD2E. MYO-101 has generated strong pre-clinical safety and efficacy data utilizing the AAVrh.74 vector system, the same vector used in the micro-dystrophin gene therapy program Sarepta is developing with Nationwide Children’s Hospital. A Phase 1/2a study of MYO-101 is scheduled to begin in mid-2018. The companies plan to report on 60-day biopsy data in late-2018 or early 2019. Additionally, Myonexus is advancing MYO-102 for LGMD2D, MYO-103 for LGMD2C, MYO-201 for LGMD2B, and MYO-301 for LGMD2L. Like MYO-101, all programs rely upon transfecting a restorative gene utilizing the AAVrh.74 vector.
Quoting from the May 3rd press release, Mr. Doug Ingram, president and chief executive officer of Sarepta, stated:
"We are very excited to enter a partnership with an option to acquire Myonexus. Myonexus and its focus on gene therapy using the AAVrh.74 vector to treat forms of LGMD aligns brilliantly with our vision to emerge as one of the most meaningful global precision genetic medicine companies by focusing on the use of genetic medicine to improve the lives of those with rare fatal diseases. We are also delighted to extend our collaboration with Dr. Rodino-Klapac, a renowned thought leader in the field of gene therapy. We share her dedication to rapidly bring life-changing medicines to children suffering and dying from genetic disease.”
DR.SSA RODINO KLAPAC LOUISE
Dr. Rodino-Klapac is a principal investigator in the Center for Gene Therapy at Nationwide Children’s Hospital and an associate professor at the Ohio State University. She has dedicated her research program to developing gene therapies treatment for muscular dystrophies. She is also the Chief Scientific Officer for Myonexus and has worked in close collaboration with Dr. Jerry Mendell for well over a decade to bring therapies to the clinic.