SAM is looking for volunteers to walk the Belfast Marathon (9 mile route) on 7th May… If you would like to take part please email info@helpsam.info…

Many thanks

Congenital Muscular Dystrophy is a devastating genetic muscle-wasting disease that presents in early childhood and results in profound muscle weakness in all skeletal muscles.  Children with MDC1A often cannot walk and have significant respiratory and eating difficulties.  There are currently no approved therapies or treatments for this form of muscular dystrophy.  

Prothelia’s mission is to develop and commercialize therapies for patients with muscular dystrophy and is a collaborative effort of expert scientists, dedicated management, and partnerships with patient advocacy groups, investors, regulatory bodies and other biopharmaceutical institutions.

“Laminin-111 has been found to be extremely effective in restoring lost muscle function in animal models of MDC1A”, states Dr. Brad Hodges, CSO of Prothelia.  “Our next critical milestones are to reengineer and optimize the genes for human Laminin-111, construct the cell-based production platform, and begin manufacturing of recombinant human Laminin-111 for the anticipated clinical trial.  The financial support from SAM will allow us to complete these milestones ahead of schedule and will accelerate our efforts to bring human Laminin-111 to patients with MDC1A.”

Prothelia’s lead drug candidate, Laminin-111, was first discovered by Dr. Dean Burkin at the University of Nevada, Reno (UNR).  UNR has licensed LAM-111 to Prothelia and we are working closely with Dr. Burkin and his staff to accelerate the development of Laminin-111 for treatment of MDC1A, Duchenne Muscular Dystrophy (DMD) and other forms of muscular dystrophy.

SAM is a “zero cost charity” meaning that no money is deducted from donations to cover salaries, administration or overheads – every penny of every pound goes towards funding research projects.

Having raised an incredible £250,000 in just over 18 months the charity is also currently funding research to evaluate 3 promising CMD drug candidates and a separate effort to identify disease biomarkers. SAM has also funded the entire set-up and running costs for a Global Patient Registry – a vital pre-requisite for future clinical trials.

EMERALD BALL RAISES OVER £86,000

The Europa Hotel played host on Saturday March 13^th 2010 to the star-studded SAM Emerald Ball. The event raised a truly staggering £86,000 which will be used to fund research projects which aim to find an effective treatment for Congenital Muscular Dystrophy (CMD).

Northern Ireland’s celebrities and glitterati turned out in force to join the event’s hosts - actor James Nesbitt and local media personality Emma-Louise Johnston - for an evening of top-notch entertainment.

Following a red carpet arrival and champagne reception guests were treated to entertainment by Matt McGinn, followed by upbeat Irish dancing with a modern twist from Celtic Storm.  Guests then enjoyed a splendid five course banquet, after which singer Oonagh Derby took to the stage, followed by local comedian Tim McGarry, who had the room literally roaring with laughter.

Jimmy and Emma-Louise then let the evening take a serious turn as they discussed the work of the charity, passionately describing the personal journey of the McCausland family and the hope that the work of the SAM charity is providing to families affected by CMD.

“I have never seen anything like this charity – what they have achieved in such a short time is spectacular…” commented host, Jimmy Nesbitt.

As the charity auction got into full swing the strength of local support for SAM became apparent. A spectacular array of items were on offer, including an original oil by celebrated local artist Terry Bradley, Rory McIlroy’s golf bag and clubs which he used as an amateur, a training session for 8 children with the Ulster Rugby Team, top local chef Michael Deane preparing a gourmet meal in the lucky winner’s home, VIP packages from Down Royal, Vistoria Square, Belfast Giants, Drumbo Park and Rally School Ireland and a stunning piece from local photographer Glenn Waddell to name but a few of the outstanding auction lots. Auctioneer for the evening was Raymond Hill of Carryduff Auctions, who not only delivered his role with professionalism and passion, but also with humour, ensuring that the auction became part of the evening’s entertainment.

The excitement in the room was palpable as Emma-Louise revealed the stunning diamond and emerald earrings which had been specially designed in celebration of the Emerald ball by Fred J Malcolm jewellers. Every female guest (and a few males!) was invited to select a beautifully wrapped box inside which one lucky winner found a message asking her to come on stage to receive her gift. Malcolm’s generosity did not end there, however, as every lady who attended the event was given a beautiful set of emerald swarovski crystal silver set earrings as a keep-sake.

Guests at the Emerald Ball then danced the night away with the amazing ‘Big Kahuna’ Band.

The staggering sum raised at Saturday night’s event will go towards research projects to help bring an effective treatment for the disease one step closer.

Sam’s mum, Tracy McCausland added:

“The work we are doing in raising money to fund research through the SAM charity gives me hope. I dream that Sam and all the other children who suffer from CMD will have a real chance of having a brighter future than the one currently predicted for them.”

All of us hope that the money raised at the Emerald Ball will help fund the research which will make that dream come true.

SAM EMERALD BALL

Please join us at Belfast’s fabulous Europa Hotel on 13th March for the SAM EMERALD BALL and celebrate St Patrick in style!!

Leading NI glossy monthly “IN Magazine” recently nominated the inaugural Emerald Ball in the category of “Most Glamorous Event of 2009”. We’re confident that this year’s EMERALD BALL will be sensational - an unequivocal highlight of the 2010 social calendar! The evening will get off to a sparkling start with a red carpet arrival and champagne reception, followed by a sumptuous five course banquet. We have a packed programme of spectacular entertainment, a few surprises and - of course - a nod to the Emerald theme! Jimmy Nesbitt and Emma-Louise Johnston will once again take the stage as your hosts for the evening.  

Thanks to your enormous generosity the 2009 Emerald Ball raised in excess of £65,000. As a uniquely ‘zero cost charity’ every pound raised through this and other events goes directly to fund research into Congenital Muscular Dystrophy.

Standard tables for the event are priced at £1000. Alternatively premium tables may be purchased at an additional cost of £250, and packages which include advertising and sponsorship are also available. For further information please email ball@helpsam.info.

SAM

December 15 2009

SAM, the local NI based charity set up in 2008 to raise funding for research into Congenital Muscular Dystrophy, announced today that they will fund grants to evaluate 3 promising CMD drug candidates in 2010: an NFKappaB inhibitor, laminin 111, and a muscle specific IgF upregulator. A separate effort to identify disease biomarkers specific to merosin deficient CMD (MDC1A) will also be funded by SAM in association with international CMD advocacy group CureCMD.

“Hope is powerful!  We believe a focused investment in science will lead to CMD treatments which will bring hope to the many thousands of families whose lives have been affected by Congenital Muscular Dystrophy.” (Gillian Garrett, Chairperson SAM) 

Each application received during this year’s grant process was subjected to a rigorous review process that included outside peer review and Scientific and Medical Advisory Board oversight. 

We would like to congratulate the scientists below.

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. 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.

How are SAM and Cure CMD collaborating? 

SAM and CureCMD have created a strategic alliance to drive towards finding treatments for the congenital muscular dystrophies (CMDs).  Using CureCMD’s infrastructure and Scientific and Medical Advisory Board led by chairman, Dr. Carsten Bonnemann and Anne Rutkowski (CureCMD), the alliance has enabled funding of key scientific projects focused upon testing 5 different drugs for the CMDs. Both organizations financially 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.

New research reveals potential treatment for congenital muscular dystrophy…

Swiss pharmaceutical company Santhera has shown that Omigapil, a drug originally developed for treatment of neurological disorders such as Parkinson’s disease, can improve symptoms of led merosin-deficient congenital muscular dystrophy (MDC1A) in a mouse model. Mice receiving Omigapil once a day had less severe symptoms of the disease when compared to mice not receiving the drug. Mice on Omigapil also tended to survive for slightly longer.

The severity of MDC1A can vary, but in the most severe cases babies born with MDC1A have reduced muscle tone and muscle weakness (sometimes called “floppy baby syndrome”). Skeletal malformations such as deformation of the spine also occur along with an inability to stand or walk, breathing problems, and it can lead to death in early life.

MDC1A is caused by mutations in the LAMA2 gene which leads to faulty production of a protein called ‘laminin-α2′. This protein is found in skeletal muscle and helps to maintain the structure of the muscle cells during contraction. Disruption of laminin-α2 levels results in muscle and nerve deterioration through a type of cell death known as “apoptosis”.

What did the research show?

In this study, researchers first sought to explain how Omigapil might be able intervene in the processes in the cells that lead to the symptoms of MDC1A. They used molecular techniques to show that an enzyme called ‘GAPDH’ is involved in the muscle cell death process (apoptosis) in mice with MDC1A. Omigapil is thought to work by directly binding to GAPDH and blocking the enzyme’s actions, and the researchers suggest this is how Omigapil could reduce muscle cell death and improve symptoms of MDC1A.

The researchers then treated a mouse model of MDC1A with Omigapil. The drug was given by mouth once a day from soon after birth. As the researchers expected, Omigapil reduced muscle cell death and protected muscle tissue. Muscle fibres in these mice were healthier and showed less damage. As a result, mice receiving Omigapil had a higher body weight, less skeletal problems, and increased movement ability. Mice on Omigapil still died very young, but on average they had a slightly longer life expectancy than those not on the drug.

What does this mean for patients?

These results suggest that it may be worth testing Omigapil as a potential therapy for MDC1A. Omigapil does not target the primary genetic cause of the disease and so it cannot completely ‘cure’ MDC1A. However, the drug does seem to effectively target processes in the cell that lead to some of the symptoms of MDC1A, meaning it may be able to slow disease progression.

Previous therapies for MDC1A have focused on ‘replacing’ the faulty laminin α2 protein with similar proteins. However there are still many technical difficulties to overcome in protein replacement therapy, especially getting the protein into all of the muscles in the body. As Omigapil is an oral drug, many of these difficulties are bypassed. An added bonus is that the development of Omigapil is already well advanced; the drug has already been tested and proven to be safe for humans in large clinical trials for Parkinson’s disease and amyotrophic lateral sclerosis patients.

Santhera has already secured orphan drug status for Omigapil and is currently defining the details of their planned clinical trial and performing additional preclinical development work which is required because the drug will be tested in children for the first time. 660,000 euro funding for the final stages of this pre-clinical work has been awarded to Santhera by French patient advocacy organisation Association Française contre les Myopathies (AFM).

It cannot be certain that Omigapil will have the same beneficial effects in humans as it has in mice. Nevertheless symptoms of the disease which improved in mice after taking Omigapil are also present in the human disease, and Omigapil is therefore a promising therapeutic contender for treatment of MDC1A.

Last week we met with David Galloway at Stormont to highlight our concerns and attempt to drive changes to the current system. There are two key areas of concern from the parent perspective - firstly the process of gaining an accurate and expedited diagnosis for these children and secondly the ongoing management of their care. At present the care (and more often than not the diagnosis) of children with neuro-muscular disease is parent-driven, although this is only in the cases where parents are well-informed and aggressive in their pursuit of proper care for their child. Referrals to Newcastle are still not being routinely made as should be the case where the local or regional system does not provide the appropriate level of service and expertise. Examples were cited from the Duchenne community where the life-expectancy of children in NI is actually significantly lower than in other areas of the UK as physiotherapy, steroid treatment and orthopedic splinting are not routinely given, and care is concentrated on chronic end-stage management of respiratory and cardiac failure. Due to the diverse clinical presentation of the Congenital Muscular Dystrophies the picture is further complicated by the need for knowledge at local level relating to the greater range of clinical management protocols which are required for the CMDs (eg earlier and more aggressive pulmonary care due to respiratory issues being more prevalent in the early stages of the disease).

The ensuing discussion led to a number of informal commitments from Mr. Galloway and his team including the review and hopefully the acceptance of the TreatNMD guidelines on standards of care, acknowledgement of the requirement for a Care Co-Ordinator whose role in the initial stages would be the identification of the necessary clinical interfaces, establishment of clear pathways and lines of communication with sub-specialists to ensure that patients are referred to and seen by the appropriate specialists at the right time, and to help families and patients to navigate the system, and the establishment of links to primary care providers in the community to facilitate more effective referrals and also provide greater education regarding NMDs. (workshops, consensus of approach etc).

It’s a start - and we won’t give up until the winds of change go gale-force! Watch this space!