HelpSAM.info Blog

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

Belfast man Nicky McMahon has for the past few months been “LOSING LBs TO RAISE £s” for SAM. He has a few lbs still to go and we would like to give him the motivation to reach his target. If you can spare a few quid to help please donate at http://www.justgiving.com/-pleasefixsam - (or click on the donate button and follow the link) Justgiving is a secure payment facility and you can donate via paypal or credit card in any currency and the charity benefits from additional gift aid if you are a UK taxpayer. Many thanks

SAM announces terrific progress towards identifying treatment options in the CMDs!

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.

We have never made any secret of the harrowing story that was the process of Sam’s diagnosis. From delayed appointments with consultants to mishandled muscle biopsy samples, lies, inaccurate information and general incompetence it horrifies me to learn that this is not an unusual tale with regard to the diagnosis and management of children with muscle disease in Northern Ireland. Indeed, the recent “Walton Report” highlighted a shocking range of shortcomings in the NHS in NI in relation to the standards of care received by children suffering from neuro-muscular disease.

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!

Well….. Over 18 months after we first found out about Sam’s condition we finally got some DNA results. They found a problem on one of the copies of Sam’s merosin (Laminin A2) gene. Basically we all have 2 copies of each gene - we inherit one from mum and one from dad. In Sam’s case it turns out that both William and I each carry a wonky gene. We are unaffected as the other copy of our gene is fine, so it enables our bodies to produce the merosin protein. Poor wee Sam has inherited both the wonky genes, meaning that he cannot produce the protein, needed to help keep the muscles healthy. They have been sequencing Sam’s merosin gene for over a year now, and they have found a premature stop codon on exon 38 of the gene (this is like finding a full stop where there should be a comma, but in the case of the DNA the body basically cannot read through the mutation and just stops producing the protein). His DNA will have to be sent now to Montpelier in France or Emory in the USA where they will utilise a different technique to try to locate the fault on the other copy of the gene. This particular fault or mutation on the gene has only been reported 5 previous times.

http://www.mda.org/research/090413lgmd-gene-therapy.html

http://www.sciencentral.com/video/2009/04/20/muscular-dystrophy-drug/

Promising things are happening in the world of MD research - the above links are to research being conducted in Limb Girdle MD and Duchenne.

The great news is that SAM will be inviting applicants for the first $100,000 SAM Translational Research Grant in August 2008.

Out of sorrow comes determination. Out of determination comes hope. Out of hope comes inspiration.

Wow - what a wonderful night - the first Emerald Ball exceeded everyones expectations in terms of entertainment value, glamour, fun - and of course - FUNDRAISING!!! I cannot thank people enough for their generosity - I think we almost set a record - we raised a whopping, massive, impressive, mind-blowing £70,000!!! The money wont be languishing in the SAM bank account for long, as this week we will be tranferring the funds for the set-up of the International Patient Registry - a necessary prequel to any research in this area… This will give scientists a database of patients across the world with CMD and will hold vital information on disease subtypes, DNA results, and disease progression. We have also committed to a $100,000 research grant which will go to tender in August with a view to kickingoff the first SAM Translational Research Grant in January 2009. An awesome achievement for a wee NI charity, and hope for Sam and other children with CMD. Thank you - from the bottom of my heart.

Tracy xxxx

Over 300 keep-fit enthusiasts saddled up to help raise funds for Struggle Against Muscular Dystrophy last Friday at the Queen’s University Physical Education Centre. Organised by Gordon Crockard of World Motorcross fame and European Enduro rider and Paris-Dakar competitor Paul McGuire, participants in the 12 hour Sponsored Spin were in the saddle for a mimimum of 1 hour with a number of people signing up for the full 12 hours!

 “We are both delighted that we were able raise over 5000 pounds for the charity while at the same time help raise the profile of the “please fix sam” campaign” said Paul.

We are delighted that Paul, Wes and Gordon are such great supporters of our charity! To date they have raised over 8000 pounds!!

A thousand thank-yous!

Tracy