Cure CMD announces terrific progress towards identifying treatment options in the CMDs!
Together, Cure CMD and S.A.M will fund grants to evaluate 5 promising CMD drug candidates: an NFKappaB inhibitor, laminin 111, a muscle specific IgF upregulator, N-acetyl cysteine and calcium handling compounds. A separate effort to identify disease biomarkers specific to merosin deficient CMD will also be funded.
Hope is powerful! We believe a focused investment in science will lead to CMD treatments. Each application received by Cure CMD during this year’s grant process was subjected to a rigorous review process that included outside peer review and Cure CMD Scientific and Medical Advisory Board oversight. We would like to congratulate the scientists below and thank all the applicants for their applications.
Anne Rutkowski, Cure CMD Chairman
Grants funded through Cure CMD and S.A.M. partnership:
Dr. Denis Guttridge, PhD: $50,000 a year for two years, Ohio State University Medical Center, Columbus, Ohio
Our laboratory has identified a molecule called NF-kappaB (for nuclear factor kappa B) which negatively impacts muscle and contributes to disease in muscular dystrophy. We have shown that drugs that inhibit NF-kappaB can improve the health of mice with muscular dystrophy.
- This grant will test whether NF-kappaB is relevant in MDC1A (merosin deficient CMD) and whether a drug against NFkappaB (NEMO binding protein) can rescue mice with MDC1A.
- We hypothesize that NF-kappaB contributes to disease in MDC1A. Using drugs to inhibit NF-kappaB might prolong the life of people with CMD.
Dr. Dean Burkin, PhD: $35,000 a year for one year, University of Nevada, Reno, Nevada
Laminin-111 is a form of laminin found in developing skeletal muscle and adult kidney and is similar to merosin (laminin-211). We have recently shown that laminin-111 can be delivered to the major muscles of a mouse model of Duchenne muscular dystrophy and prevents muscle disease. Our preliminary results show that intramuscular injections of laminin-111 protein can also prevent muscle disease progression in a mouse model of MDC1A.
- We will use MDC1A muscle cells to determine if the mechanism of action of laminin-111 is conserved between mouse and human muscle cells. A separately funded effort will identify if systemic therapy with laminin 111 improves the MDC1A mouse model.
- Together, results from both studies will determine if laminin-111 protein therapy will serve as a novel and effective treatment for people with MDC1A.
Dr. Sweta Girgenrath, PhD: $50,000 a year for two years, Boston University, Boston, Massachusetts
Preliminary work demonstrates that IgF upregulation improves the health of the MDC1A mouse model.
- In this study, mice with MDC1A will be genetically induced to have elevated levels of IgF at the muscle to determine if there is a definitive positive effect. The potency of this effect will be gauged in isolation and in combination with anti-apoptotic interventions (doxycycline and Bax knockout).
- Subsequently, both mice and human cells with MDC1A will be tested with a compound that increases IgF to determine how and if the compound represents a therapy in CMD.
Dr. Ana Ferreiro, MD, PhD: $28,500 a year for one year, Institute of Myology, Paris France
Preliminary work demonstrates a possible mechanism for SEPN1 related myopathies involving oxidative reductive stress handling. Based on this mechanism, N-acetyl cysteine represents a potential treatment option.
- In this study, the mouse model for SEPN1 will be treated with NAC to understand the treatment effect and assess various dosage potencies.
- Human muscle SEPN1 cells will be treated with a different drug: calcium handling drugs to assess their therapeutic potential.
- Additional partners and pathways that might contribute to disease in SEPN1 will be studied.
Dr. Jim Collins, MD, PhD: $50,000 a year for one year, Cincinnati Children’s Hospital Medical Center, Cincinnati Ohio
- The aim of this study is to obtain the gene and protein expression profiles in individuals with MDC1A.
- Serum and urine proteomic profiles in individuals with MDC1A will be assessed with proteomic technology. Blood genomic profiles will be assessed with transcriptomics technology. MDC1A will be compared to controls in order to identify unique protein and gene expression profiles.
- Other studies using this technology have found unique blood gene expression profiles in other diseases including Down syndrome, migraine, stroke, and Duchenne muscular dystrophy. Our central hypothesis is that MDC1A, a group that is clinically well defined and genetically confirmed, has a unique gene and protein expression profile.
- The preliminary results from this study will be used to drive validation studies that we hope will lead to further understanding of the MDC1A disease pathways and the discovery of a unique biomarker that could be used in future clinical trials.
Who is S.A.M? S.A.M stands for Struggle Against Muscular Dystrophy and is a Northern Irish nonprofit advocacy launched by 2 parents whose son has CMD. To read more: www.helpsam.info
How are Cure CMD and S.A.M. collaborating? Cure CMD and S.A.M have created a strategic alliance to drive towards finding a treatment and cure for the congenital muscular dystrophies (CMDs). Using Cure CMD’s infrastructure and Scientific and Medical Advisory Board led by chairman, Dr. Carsten Bonnemann and Anne Rutkowski (Cure CMD), the alliance has enabled funding of key scientific projects focused upon testing 5 different drugs for the CMDs: an NFKappa B inhibitor, laminin 111, insulin like growth factor (IgF), N-acetyl cysteine and calcium handling compounds. Both organizations support the CMD International Registry (CMDIR) to identify all individuals globally with CMD, www.cmdir.org
We would like to thank the Cure CMD Scientific and Medical Advisory Board for their tremendous work in reviewing and discussing the grant applications: Dr. Carsten Bonnemann, Dr. Francesco Muntoni, Dr. John Porter, Dr. Volker Straub, Dr. Markus Ruegg, Dr. Edward Kaye and Dr. Alexandre Mejat. We welcome our newest SMAB member: Dr. Petra Kaufmann.
We would also like to thank the 34 outside peer reviewers who provided timely constructive feedback and review of the grant applications.