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2013 MD South Australia Research Reports Once again, it is my great pleasure to be able to write these Research Reports for you. In this instance they will mainly be taken up with news from clinical/scientific research conferences that I have attended since writing my previous annual report, backed up in part by information from medical/scientific journal articles that I have read in the meantime. Report from the 2012 World Muscle Society Congress, Perth, WA
WMS 2012 - In the second week of October last year, I attended the 17th International Congress of the World Muscle Society (WMS 2012) in Perth, WA. Well over 500 registered delegates were present at the Congress which was held at the Perth Convention Centre. Particular Highlights from the Conference were: Dr Kevin Campbell, University of Iowa, USA – skin cells known as "fibroblasts" have many of the proteins and enzymes associated with muscle cells and so can be used to study some muscle diseases and potential therapies. Skin biopsies are simple to obtain compared to muscle and the fibroblasts grow well in tissue culture. So, using these cells it can be shown that serious NMDs such as the Dystroglycanopathies are amenable to therapy with certain drugs and special sugars. Dr Kevin Flannigan, Ohio State University, USA – it is now almost unethical not to undertake newborn screening for DMD. Both the necessary CK and DNA tests can be performed on a single dried blood spot (the same heel prick spot used for the Guthrie test and others), and it is becoming less expensive by the day. The cost of measuring the CK level is just a few dollars and the DNA test to capture most cases was about $150 for Dr Flannigan's screening trial. It is worth noting that Dr Nigel Laing, in Perth, is a strong advocate of this screening and that I promoted its introduction in Adelaide in the mid 1980s. Our initial logic related to the frequent birth of more than one boy with DMD in a family before the eldest could be diagnosed, thus giving parents no opportunity, had they known, to plan their subsequent family. This reasoning is now coupled with the almost certain availability of treatments, if not cures, for DMD within a few years – if the treatment is begun early enough. Dr Katherine Howell, Royal Children's Hospital, Melbourne, raised the often taboo subject of developmental delay and cognitive impairment in DMD. It is now apparent that genetic variations in both the mutated dystrophin and in modifier genes are responsible for the large differences in cognitive abilities of boys and men with DMD or BMD and of girls and women who are carriers. These unpredictable differences make counselling difficult in these families. Drs Jocelyn Laporte and Vincenzo Nigro explained how 40% of people with NMDs still have no firm diagnosis by genetic mutation, although eventually (but not yet) this may feasibly be solved by whole genome sequencing at a reasonable cost, this is not yet the case. Exome sequencing, that is, sequencing that part of the genome that contains all the known genes, is now frequently performed at a cost of around $1,000 or less. Sequencing of the 100 genes most likely to be mutated in the most common NMDs is even less expensive where a particular diagnosis is not obvious (the signs and symptoms of some NMDs being identical). [In this regard, at the more recent WMS2013 Congres in Asilomar, California, Dr Lou Kunkel cautioned that the amount of data generated by whole genome sequencing would be overwhelming, filling 1Tb of disk space per person. Permanent hacker-proof storage of this genetic data, its interpretation and the counselling of individuals with respect to its content represents a currently insurmountable challenge.] Various speakers described research on promising therapies for many different NMDs, from DMD through Limb Girdle MDs and Facioscapulohumeral MD to Myotubular Myopathy and even muscle wasting due to aging. [More up-to-date information on some of these is provided in my report from the WMS2013 Congress, below.] Of considerable importance, given how relatively common Myotonic Dystrophy is among NMDs, Dr Karian Wahbi, from Paris spoke about prevention of sudden death in a population of 914 cases with Myotonic Dystrophy type 1 (DM1). There was a 70% reduction in sudden deaths in those with a pacemaker or an implanted cardiac defibrillator (ICD). An ICD was also recommended for cases of Desminopathy. A number of new and unusual NMDs were described. Drs Peter Hackman from Helsinki, Finland and Velina Guergueltcheva from Sofia, Bulgaria, reported on strange NMDs affecting mainly the muscles of the hands and feet. In one of these, Welander Distal Myopathy, the mutation occurs in an RNA-binding protein (TIA1) that is involved in "stress granules" in cells. Mutant TIA1 increases the numbers of these stress granules. In another case, Dr Carole Hedberg from Gothenberg, Sweden, described finding a genetic mutation in titin, the largest of all known proteins and essential for normal muscle function. This mutation in titin causes an unusual hereditary NMD associated with early failure of respiratory muscles. Along the same lines, Dr Baziel van Engelen from Nijmegen, The Netherlands, resolved a mystery regarding the NMD known as sporadic Inclusion Body Myositis (s-IBM), an autoimmune disease, where the body's immune system makes antibodies to attack its own tissues. His study resulted in the discovery of one culprit antibody (anti-Mup44) in one third of those tested who had s-IBM. Drs Nigel Laing and Kristen Nowak from, Perth, WA discussed NMDs involving the protein, Actin. Actin and myosin are the power producing proteins of muscle, the actin filaments like the "ropes in tug-of-war" and the myosin molecules like the people pulling on the rope. Mutations in either of these proteins cause NMDs. Most actin mutations result in actin accumulation in clumps inside muscle cells (like tangles of rope) and disrupt normal function. These accumulations, known as nemaline bodies, are associated with the Congenital Myopathy, Nemaline Myopathy. Cardiac muscle actin can rescue the skeletal muscle defect in some cases. Also on muscle proteins, Dr Gaëlle Blandin from Généthon at Evry, France, introduced a new concept for skeletal muscle, the "Interactome", in which protein-protein interactions are investigated to attempt to understand the role of each protein in their environment inside muscle fibres. In all, 1,018 different muscle proteins were studied and found to be involved in 1,492 different interactions only 5% of which were previously known. With regard to patients/carers, Dr Janbernd Kirschner from Freiburg, Germany, presented results of Care-NMD questionnaire with 42 questions sent out to 1,600 people with NMDs/carers. There were 1,071 returned completed. Of particular significance to MDSA, one of the questions asked was: If you do not attend neuromuscular clinics, why not? Adults with NMDs answered that the clinics were too far away or that they didn't know they existed. Dr Thomas Segersen from Stockholm, Sweden, spoke about Standards of Care, in particular relating to clinical trials where everyone in the trial must be treated with the same standards of basic care or any test of a new therapy is likely to be invalid. Of course the highest possible standards of care should be aimed for in every case but, how can this be achieved? In general, by establishing standards of care guidelines for each specific NMD, particularly, these guidelines must be developed with client representation and they must be "client friendly". Then they must be tried and assessed, discussed and modified in successive rounds of development until there is a consensus regarding their suitability and value based on genuine evidence. Standards of care guidelines have been published for several NMDs, notably Spinal Muscular Atrophy, DMD, Congenital Muscular Dystrophy and Congenital Myopathy with others partially complete or in process. In this regard, Dr Susan Iannaccone from Dallas, Texas, USA, discussed the importance of non-invasive ventilation by CPAP or BiPAP. Equally, monitoring for sleep disordered breathing is important. It was suggested that this should be checked at least annually. Report from the 2013 AOMC Scientific Conference, Xi'an, China
AOMC 2013 – This year in early June, as usual, I attended the Annual Scientific Conference of the
Asian and Oceanian Myology Center (AOMC) held, this time, in Xi'an, China.
Dr. Dingguo Shen (AOMC Executive Board Member), as Honorary Chairman of the Local Organising Committee, together with Chairs, Drs Liying Cui and Chuanqiang Pu and a large team of committee members, organised the meeting for AOMC with the Chinese Society of Neuromuscular Diseases, the Chinese Society of EMG & Clinical Neurophysiology, the Chinese Medical Association, the Shaanxi Province Medical Association and the Japan Foundation for Neuroscience and Mental Health as co-organisers. It was attended by 280 participants from 11countries, mainly China, of course, but also from Japan, Korea, Singapore, Thailand, Australia, India, Malaysia, The Philippines, Iran and the United States. Ten young individuals with interests or involvement in the neuromuscular field were awarded Fellowships to attend the conference through grants from the Japan Foundation for Neuroscience and Mental Health, as facilitated by AOMC president, Dr. I Nonaka. Dr. Xusheng Huang chaired the Opening Ceremony, introducing local dignitaries and special guests who welcomed the attendees. AOMC President, Dr. Ikuya Nonaka from the National Centre for Neurology and Psychiatry, Tokyo, then opened the scientific program with a presentation on "Inclusion Body Myositis (IBM): Clinical and Pathological Aspects" in the first symposium which was entitled, Inflammatory Myopathies. Because it is possible to treat many inflammatory myopathies successfully and inexpensively with anti-inflammatory drugs, this symposium was of considerable interest for the Asian region. Other speakers in the session covered the diseases, Polymyositis and Dermatomyositis. A symposium on Metabolic Myopathies followed with particular emphasis on Dr. Chuanzhu Yan's presentation on a disease known as Multiple Acyl-CoA Dehydrogenation Deficiency that is relatively common (compared to other rare NMDs) in China and is treatable with Vitamin B2 (riboflavin). Dr. Yuh-Jyh Jong from Taiwan, then described his successful experience of neonatal screening and enzyme replacement therapy for Pompé Disease in Taiwan. The third symposium on the first day of the conference provided extremely encouraging updates on therapeutic trials. Dr. Shin'ichi Takeda gave an update on Exon Skipping therapy for Duchenne Muscular Dystrophy with the good news that a Japanese pharmaceutical company, Nippon Shinyaku, is about to trial a new drug to skip exon 53 in DMD. Another company, Daiichi-Sankyo, is preparing a drug to skip exon 45. He also announced that by April 2013, the Japanese DMD Registry in Japan had included more than 1050 patients. Advances in viral and cell-based therapies for DMD were presented by Dr Dongsheng Duan from the University of Missouri, USA, who described very promising results in muscular dystrophy dogs. Dr. Katsuhisa Ogata from the Higashisaitama Hospital in Saitama, Japan, then gave an update on the management of DMD patients in Japan. While much progress was continuing with non invasive ventilation, appropriate food preparation and cardiac care, new difficulties were emerging along with the increasing life spans. Lung, intestine and kidney problems were becoming a concern requiring standards of care to be revised for older patients. [See also Dr Segersen's comments in my report from the WMS2012 Congress.] Dr Ogata finished with a quotation from Xuanzang, the Chinese monk who travelled to India and brought Buddhism back to China almost 1,400 years ago. Just as with our present ability to understand and treat NMDs, the quotation says, approximately: "Our journey has not ended, it is still under way." On the morning of the second day, the conference was again devoted to symposia, the first being on diagnostic techniques for NMDs. Among the presenters, Dr. Dingguo Shen spoke on the use of MRI scans in detecting muscle pathology, Dr. Raymond Rosales from The Philippines discussed the diagnosis of hyper-excitable muscle conditions, and I spoke on diseases of muscle involving ion channels and how to diagnose them. The NMD now known as GNE Myopathy originally went by many different names, including Nonaka Myopathy (named after its discoverer, Dr. Ikuya Nonaka) and, also, Hereditary Inclusion Body Myopathy (hIBM). It featured in the second morning symposium with Dr. Ichizo Nishino presenting encouraging preclinical trial results using the novel sugar, sialic acid, essential for normal muscle structure but missing in the disease. Accounts of GNE Myopathy in China, Thailand, Malaysia and Korea followed. As in previous AOMC Meetings, there was a Muscle Pathology Case Conference in which the characteristics of unusual or undiagnosed cases were presented for all in attendance to consider.
There were also188 clinical and scientific research posters describing new studies in most areas of
NMD. Ten prizes were awarded for the best examples of this new research. I have continued as one of
the Australian representatives on the AOMC Executive Board. At its meeting, members agreed to
accept the proposal from The Philippines to hold the 13th Annual Scientific Meeting of AOMC in
Davao.
Report from the 2013 World Muscle Society Congress, Asilomar,
California
WMS 2013 – Immediately before the World Muscle Society (WMS) Congress (in early October), I
visited the laboratories of Drs Jie Zheng and Tsung-Yu Chen and held meetings with them and my
former student, Dr Linlin Ma at the University of California, Davis. Earlier in the year I wrote a
chapter, "CLC-Related Proteins in Diseases", for the Handbook of Ion Channels being edited by Dr
Zheng and expected to be published next year. Drs Zheng, Chen and I have undertaken closely
complementary research on the skeletal muscle chloride channel and similar chloride channels over
many years. Although I knew of his highly regarded research from much earlier, I first met Dr Chen
in Taiwan in 2002.
The 18th International Congress of the WMS was held in Asilomar, California at the splendid Asilomar Conference Grounds on Monterey Peninsula. In the early 20th Century, these facilities were built among the sand dunes and native vegetation adjacent to the beach by the YWCA as a young women's retreat. For any of you interested in golf, it is just a few miles north of the famous Pebble Beach Golf Course. There were some 550 registered delegates in attendance despite the US Government closing down and preventing lectures or other presentations by those scientists and clinicians who worked for the National Institutes of Health or the Centres for Disease Control. In fact, any of these researchers who had arrived at Asilomar the day before the Congress began, were made to fly home that evening under threat of two years gaol if they spoke of their work during the Government shutdown. Highlights of the conference: Myomatrix is the thin fibrous felt-work enveloping individual muscle fibres through which they are attached to connective tissue that acts as the overall support scaffolding between muscle fibres. If the myomatrix is defective, muscle cells can be damaged resulting in several rare forms of Muscular Dystrophy. Numerous proteins, including laminins, perlecan and agrin comprise the matrix and mutations in many of them are associated with the different MDs. Drs Peter Yurchenko, Rutgers University, USA, Elizabeth McNally, University of Chicago, USA, Marcus Ruegg, University of Basel, Switzerland and Paul Martin, Ohio State University, USA, gave research presentations on these matrix proteins in health and disease and potential approaches to their respective therapies. In particular, therapies (including gene therapy) that increase levels of the enzyme, GALGT2, protect muscles in the presence of various MDs in animal models. Each year, new rare NMDs are characterised and this year has been no exception. Drs Debbie Hicks and Volker Straub from the Newcastle Institute of Genetic Medicine and their colleagues have described new disorders with similarities to Bethlem Myopathy and Ulrich MD that are associated with mutations in the collagen 12 gene, collagen 12 being an essential protein in the connective tissue surrounding muscle and skin cells. A skeletal muscle myopathy in which the heart muscle is also involved was described by Dr Montee Olivé from the Llobregat Hospital, Barcelona Spain. It is caused by abnormal accumulations of MuRF proteins in muscle fibres. In a session discussing immunity in relation to NMDs, Dr Olivier Benveniste of the Intitute of Myology, Paris, concluded that the protein aggregates seen in muscle cells of sIBM are not the cause of the inflammation in these muscles but that the inflammation comes first. In this regard, he suggests that the process is more like that occurring in Multiple Sclerosis. The organiser of the Asilomar Congress, Dr Dianne Shelton, is a vet based at the University of California, San Diego. She has made very important contributions to our understanding of human NMDs by studying naturally occurring animal NMDs. Her major studies have been on autoimmune diseases such as Myasthenia, Myositis and sIBM and their treatment in dogs and cats using the same drugs as in humans. New and better treatments for humans may be found by testing them first on these animals. There was a lot of good news regarding Spinal Muscular Atrophy (SMA). Much of this was delivered in a lecture by Dr Arthur Burghes of Ohio State University, USA. He outlined a new understanding of why some people with the SMN (Survival Motor Neurone) mutations that normally cause severe disease can be only mildly affected or unaffected. This depends on what is called the "Copy Number" of a related gene, SMN2. The more copies of this SMN2 gene in a person's genome the more resistant they are to the bad effects of an SMN mutation. Dr Burghes and a colleague, Dr Sandra Duque, provided extraordinary evidence of therapy in SMA mice (one procedure increasing lifespan from 14 to 365 days) and in SMA piglets where the symptoms of the disease seem to be totally corrected. Several drugs (including AONs) were quite effective but gene therapy using a viral vector was best, especially when tested at an early stage of the disease indicating that there might also be a critical age window for treatment in humans. Dr Kathy Swoboda from the University of Utah, Salt Lake City, USA presented the results of a Phase 1 clinical trial of the AON drug ISIS-SMNRx from ISIS Pharmaceuticals. Although a Phase 1 trial is only designed to test for safety and possible side effects at low drug doses, at 14 months after a treatment involving a single injection of the drug, most children in the trial had improved motor function and none had declined. There were no safety issues. On another front, Dr Kathy Matthews from Iowa, USA, spoke about "MD starNET" an initiative funded by the US Centres for Disease Control and Prevention. MD starNET aims to find everyone with DMD or BMD, born after 1981, living in those US states that have joined the organisation. To this statistical data will be added information about the health and services needs of these people. This knowledge, which should be widely applicable, is expected to inform all stakeholders from those with these diseases and their parents/carers through doctors, allied health workers, public health officials and educators to not-for-profit support organisations. It is hoped that this data gathering will be extended to all NMDs in due course. Meanwhile, Dr. Matthews observed that parents are the first to recognise neuromuscular problems in their children but that there may be a significant delay before they mention it to a doctor or health care worker and then another significant delay before it is taken seriously enough to refer to a neurologist. With potential therapies becoming available soon and early intervention essential, new ways to educate family doctors, in particular, about rare NMDs must be developed with information/videos, etc., available on relevant websites. Another consortium of interest is Bio-NMD, a group with industrial and university research group partners spread across several European countries and the UK. It is led by Dr Alessandra Ferlini from the University of Ferarra, Italy. Dr Ferlini addressed the need for new "biomarkers", naturally occurring substances in the body that might, for example, indicate whether muscles are responding to a therapy before any improvement in function is obvious. She stressed that new biomarkers would be especially important in allowing short duration clinical trials so that trial "burnout" by people with NMDs and their parents and carers could be avoided and potential new therapies could be tested more quickly. Others agreed that three month safety trials should be sufficient rather than the present six to nine month trials demanded by governmental regulatory agencies. An update on clinical trials of treatments for DMD was presented by Dr Francesco Muntoni from University College London. As I have mentioned in previous reports, "myostatin" is the factor that prevents overgrowth of normal muscles. Inhibitors of myostatin have potential to enhance growth where counteracting wasting of muscles is occurring as in the MDs. A phase 1 trial in humans is under way. Invasion of muscle by inflammatory cells is a feature of MDs. Powerful new anti-inflammatory drugs are also being tested in boys with DMD. Halo Therapeutics HT-100 is in Phase 1b clinical trial. Because muscle blood flow seems to be reduced in DMD, the blood flow enhancer, Tadalafil, is in Phase 3 clinical trial. For many years it has been known that the protein, utrophin, can replace dystrophin and allow almost normal muscle function in dystrophic mice. Now a drug that increases utrophin production, Summit C1100, is in Phase 1b trial in DMD boys and is expected to enter Phase 2 clinical trial next year. Meanwhile, Ataluren is being further investigated despite failing to produce truly significant improvement in a very large international clinical trial in DMD boys. The results in clinical trials using AONs for DMD have been mixed recently. As of the end of September, PRO051 (Drisapersen) from Prosensa/GlaxoSmithKline has been found to be no better than placebo in a lengthy trial – a great disappointment. Final results from the Sarepta/AVI Biopharma trial of AVI-4658 (Eteplirsen) are still being awaited, although after 96 weeks of trial the condition of the boys seems to be stable rather than worsening. This is encouraging but questions remain as to why only stabilisation has been seen and there is no obvious improvement. It seems to take forever from the discovery of a disease mechanism to clinical trials for its treatment but I had anticipated in previous Annual Research Reports that this might not be so for Myotonic Dystrophy (DM types 1 and 2). Still, it is more than 10 years in this case and again, as presented at the Congress by Dr Charles Thornton of the University of Rochester, USA, successes have been seen in treating mouse models of the disease but AON drugs suitable for clinical trials in humans are only now being developed by companies such as ISIS Pharmaceuticals. Advances in gene therapy were presented by Dr George Dickson from the University of London who encouraged us all with the news that the first ever gene therapy by viral vector had been licensed for use in Europe. While this viral "drug", "Glybera" (from UniQure, formerly Amsterdam Molecular Therapeutics), is not a treatment for an NMD, other European organisations including Généthon in Évry, the Paris-based Institute of Myology and Atlantic Gene Therapies in Nantes are hard at work developing similar strategic approaches to NMD therapies. In particular, a short version of the dystrophin gene produces a microdystrophin that can be virally delivered to muscle. It has been shown to improve muscle strength substantially in MD dogs without initiating an immune response to the virus or to the new microdystrophin. Dr Anna Buj-Bello from Généthon described a very promising virally-mediated gene therapy for Myotubular Myopathy that is capable of an amazing transformation of dogs in which this disease is also naturally occurring. At the same time, according to Dr Judith van Deutekom from Prosensa Therapeutics in Leiden, The Netherlands, rapid advances are occurring in peptide-AON exon skipping drugs that are now more readily able to penetrate the diaphragm muscle and the heart, cardiac and respiratory muscles being important targets for therapy in NMDs. Many other exciting therapeutic approaches were presented in lectures and poster sessions, too numerous to describe in detail here, except to mention, briefly, that Dr Nathalie Goemans from Leiden University indicated that the Prosensa drug PRO044 is ready for clinical trial in DMD. The genetic mutation responsible for a most unusual disease, termed "Strongman Syndrome", was reported by Dr Bernard Brais from Jonquiére, Québec, Canada. A large French-Canadian family is involved. They are all immensely strong, a young girl able to lift 200 kg at the age of 7. The men tend to take on heavy labouring jobs that no other men could perform but, unfortunately, their disease is complicated by increasing pain and eventual rapid fatigability so that by their 40s they can no longer work. Also from North America, Dr James Dowling from the University of Michigan gave an account of the discovery, via work on zebrafish muscle, of the gene involved in the disease known as Native American Myopathy which affects members of the Lumbee Tribe of North Carolina. Especially interesting to my own research field of NMDs caused by ion channel defects, Dr Stephen Cannon from University of Texas South Western, USA, showed his findings in the late-breaking news poster session that described a novel treatment strategy for Hypokalemic Periodic Paralysis by inhibition of a chloride transporter. Dr Cannon and I had a long and useful interchange about NMDs caused by ion channel defects and the potential for their treatment. I was also very interested in another poster presentation, from Dr Dae-Song Kim and his junior colleague Dr Jin-Hong Shin from Pusan University, Korea, who asked for my advice about their research on mutations in the muscle chloride channel gene, CLCN1, which is responsible for several kinds of Myotonia. Of considerable significance to the screening of genes for disease-causing defects, some so- called "synonymous" variants (previously believed to be benign) are now known to be responsible for mRNA splicing alterations that are associated with pathology. Just this year variants of this kind have been associated with a congenital form of Myasthenia in humans and with Myotonia in the Murrah breed of water buffaloes. When I discussed the possibility with Dr Nigel Laing that many mutations previously believed to be benign might, in fact, be disease-causing, he remarked, "Yes. It's something that keeps me awake at night." Other News: Among many organisations raising funds for NMDs that I have heard about in recent times there are some that were new to me: "Cure CMD" for Congenital Muscular Dystrophy research based in Olathe, Kansas, USA "Building Strength" for research into Nemaline Myopathy and other Congenital Myopathy research, based in Palo Alto, California, USA "Charley's Fund" for DMD research based in Great Barrington, Massachusetts, USA "Patients Association for Distal Myopathies" based in Hikone, Japan "Matt's Promise Foundation" mainly supporting DMD research based in Brooklyn, New York What is very worrying to me is that some organisations of this type raise considerable funds, sometimes amounting to millions of dollars, but have as few as one or two medical/scientific advisory board members. This can, and has in the past, led to enormous grants being directed towards "hobby-horse" research and questionable prospects for therapy. One of the most interesting research articles that I have read this year was written by Dr Jeannette Erdmann from the Institute for Genomics at the University of Lübeck, Germany. Dr Erdmann gives an extraordinary account of her own life beginning with difficulties running and climbing stairs from the age of four. Some years later, after many different medical investigations, she was diagnosed as having a muscle disease of unknown type and during her education she resolved to become a molecular geneticist and determine the basis of her own disease. She eventually graduated from university with a PhD (although requiring a ventilator at night) and worked as a post-doctoral fellow, assistant professor, associate professor and, finally, full professor. From minor wounds associated with growing up and as a sequel to multiple muscle biopsies, she knew that she had an abnormal skin scarring condition known as "keloid", but only at the age of 45 did she learn from her mother that she had had a hip dislocation when two years old. The new information regarding "hip dysplasia" along with "keloid" and "muscular dystrophy" enabled her to Google these terms and find references to Bethlem/Ulrich congenital muscular dystrophies. Since these are genetically-determined Neuromuscular Diseases (NMDs), she immediately decided to have her exome sequenced with the result that it showed the cause of her disease – a mutation in her collagen six gene. Many myths were dispelled by this: her disease had not been inherited from her parents, nor had it been caused by a vaccination, by a poison or by a childhood bout of the flu. It was no one's fault, but rather a spontaneous mutation, an accident of nature. The new knowledge allowed her to understand her disease and her prognosis and, along with her doctors, to take possible future complications into consideration and to hope for potential therapies. Finally, I shall only briefly comment on Australian NMD research. Since its recent establishment, the members of the Australian Neuromuscular Network (ANN) in New South Wales, Victoria and Western Australia have made considerable progress towards coordinating clinical research and clinical trials in Australia. Much of this is outlined in the ANN Annual Scientific Report for 2012 which is available to be downloaded from their website at: http://www.ann.org.au/annual-scientific-report-2012/ Although the ANN includes NMD researchers in most Australian States and New Zealand, it is disappointing that this first Annual Report only includes details of the projects of several young researchers and that information on major projects, senior researchers and clinical trials is sketchy. From this Report, it is apparent that large NMD research groups in well-known research institutions are reasonably well funded via Commonwealth NHMRC research grants. Essential, basic research on neuromuscular function and disease is, however, inadequately funded in Australia. Even highly internationally regarded independent researchers in these fields at institutions across the country are missing out on Australian Government funding. In this regard, our Association, MDSA, has this year attempted to revitalise its funding of local NMD research. A Subcommittee of the MDSA Board was established to promote NMD research by undergraduate students in South Australian hospitals, universities and other research institutions. Our Research Subcommittee requests and receives advice from MDSA's Medical and Scientific Research Advisory Committee, composed of more than a dozen senior South Australian clinicians and scientists who are knowledgeable of, or who have experience in, NMD research. It is anticipated that the reinvigoration of MDSA's past research culture will lead to renewed interest in NMD research in South Australia and the initiation of larger projects able to be assisted by future research funding from MDSA. Professor Allan Bretag Director of Research

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