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The National Institute for Health and Care Excellence (NICE), the U.K. agency that decides on the cost-effectiveness of therapies for inclusion in the public health system of England and Wales, is recommending against Spinraza (nusinersen) being offered to treat people with spinal muscular atrophy (SMA). This stance, released as “draft…

At sunset on the second Saturday of every August, it’s a tradition to light candles in memory of those who have died of spinal muscular atrophy — and to honor those currently living with the disease. Cure SMA says the candle-lighting ritual — which this year falls on Saturday, Aug. 11 — is only one way to spread the word during SMA Awareness Month. Others include attending an Awareness Day with a local major or minor league baseball team, requesting a proclamation from state or local government, hosting an awareness-themed fundraiser, contacting local media or celebrities, and participating in social media awareness efforts. Upcoming baseball games with an SMA Awareness Month theme will be sponsored Aug. 19 by the Chicago White Sox at Guaranteed Rate Field; Aug. 20 by the Boston Red Sox at Fenway Park; Aug. 24 by the Arizona Diamondbacks at Chase Field in Phoenix; Aug. 26 by the New Hampshire Fisher Cats in Manchester; and Aug. 26 by the Tampa Bay Rays at St. Petersburg’s Tropicana Field. SMA, the leading genetic cause of death for infants, affects the motor nerve cells in the spinal cord, robbing patients of the ability to walk, eat or breathe. About one in 11,000 babies is born with SMA; nearly eight million Americans are genetic carriers. Cure SMA had a major breakthrough in December 2016, when the U.S. Food and Drug Administration (FDA) approved  Spinraza (nusinersen), manufactured by Biogen. The FDA approved Spinraza without restrictions, and insurance generally covers 90 percent of cases for types 1, 2 and 3. Cure SMA now represents about 7,000 of the nation’s estimated 10,000 SMA patients, according to a recent speech by its president and CEO, Kenneth Hobby. The Chicago-based nonprofit — founded in 1984 — operates on an annual budget of $11 million. Hobby said it has spent $70 million to date on research, and some 4,000 families benefit from its services, Each year, the organization asks supporters to submit their SMA Awareness Month photos to its Facebook page. The group can also be tagged on Twitter and Instagram using the #cureSMA hashtag. Alternatively, photos may be emailed to [email protected] with “SMA community album” in the subject line. For more information, visit Cure SMA’s events calendar, download an awareness and advocacy kit (including key information about SMA that can be useful when composing a blog post or sponsor request letter), or request a medical professional awareness kit to share with primary care providers, neurologists, nurses or therapists. In Australia, where the government recently authorized insurance coverage for Spinraza for people under 18, Melbourne-based SMA Australia will host its inaugural SMA 24-Hour Challenge on Aug. 30. The organization supports people living with SMA through its cough assist and well-being programs, as well as through palliative care. “Our federal government has done an incredible job to make the drug accessible to children, but more needs to be done for adults,” said SMA Australia CEO Juli Cini, who lost two children to the disease. “I encourage everyone to get behind our 24-Hour Challenge, which will further help us in our work that supports Australians living with SMA and their families.”

The Institute for Clinical and Economic Review (ICER) will compare the clinical effectiveness and value of the only approved disease-modifying treatment for spinal muscular atrophy (SMA) —  Spinraza (nusinersen, by Biogen) — and an investigational gene therapy showing promise in advanced clinical trials — Novartis‘ AVXS-101,…

Researchers at Mizzou — the University of Missouri — have started a new company, Shift Pharmaceuticals, to test the clinical effectiveness of a molecule that may help improve the outcomes of people with spinal muscular atrophy (SMA). SMA develops due to mutations in the survival motor neuron-1…

A newly identified mutation in the DYNC1H1 gene causes a rare form of spinal muscular atrophy known as SMA with lower limb predominance (SMA-LED), which is associated with learning difficulties and brain malformations, according to a…

The degree of motor skills, and the intensity of feelings of depression and fatigue influence the degree to which adults with spinal muscular atrophy (SMA), regardless of subtype, participate in and enjoy the social and professional activities of daily life, a study from the Netherlands reports. The study, “…

A physiotherapy program that alternates whole-body vibration with intensive rehabilitation shows potential to improve motor function and mobility scores in children with SMA type 2 and 3, a study reports. The program combines in-patient neuromuscular interval rehabilitation with home-based whole-body vibration to address the progressive loss of muscle strength caused by SMA. Studies in both SMA patients and animal disease models suggest that targeted exercise may improve muscular strength and motor function. Research focusing specifically on whole-body vibration has also shown a potential to improve neuromuscular function in children. This technique induces reflex-based muscle contractions, producing involuntary muscle contractions and providing positive feedback mechanisms that strengthen muscles.  Whole-body vibration is also thought to be faster and safer than regular exercises alone. The program was tested in an observational study at University Hospital Cologne, Germany, involving 38 SMA children (mean age, 4.64). It was composed of two inpatient stays — the first for 13 days of inpatient training, then three months of at-home training, followed by a second six-day inpatient stay. Finally, patients had six months of home rehabilitation before  final assessment of improvements. The in-patient stay involved four-to-five hours of daily goal-oriented physiotherapy, with or without the whole-body vibration apparatus. During this time, families and caregivers were trained on using the vibration apparatus at home. During home training, a side-alternating whole body vibration device was used with standard exercises, such as standing, sitting, and the 4-point position. Vibrations were applied through a vibrating surface that mechanically stimulates the child on its platform, and induces reflex-based muscle contractions. Each whole-body vibration session takes about three minutes and are repeated three times. Children were  assessed for changes in motor function using the Gross Motor Function Measure (for those assessed before 2011) or the Hammersmith Functional Mobility Scale (for post-2011 assessments).  In total, 14 children were available for full evaluation — made at the beginning, after six months of home-based training, and after six months of follow-up — using the Gross Motor Function Measure, and 11 using the later measure, the Hammersmith Functional Mobility Scale. Hammersmith is a scale of 20 activities that is specifically designed for SMA type 2 and 3; the Gross Motor Function was designed for children with cerebral palsy, but has been applied to other diseases. Data showed that whole-body vibration assisted training improved both motor function and mobility, with further benefits seen after the intensive training period. Eight of 11 children (72.7%) had a more than two-point improvement in the Hammersmith Functional Mobility Scale score, while the other four showed an increase between 0 and 2 points. These point increases, the researchers noted, were significantly higher than what would be expected based on natural improvement over time (10%). Somewhat similar improvements in muscular strength and function were also seen in six of 13 children assessed under the Gross Motor Function Measure — but the study did not detail these at length.

Spotlight Innovation announced that the nonprofit Cure SMA has awarded $300,000 to Prof. Kevin Hodgetts, of Brigham and Women’s Hospital in Boston and a Spotlight research collaborator, for the preclinical development of the potential therapy LDN-5178 for spinal muscular atrophy. Hodgetts' project is titled "Pre-Clinical Development of LDN-5178 for the Treatment of SMA." Spotlight Innovation is a pharmaceutical company that licensed the worldwide development and commercialization rights for LDN-5178 from the Indiana University Innovation and Commercialization Office. Individuals with two faulty copies of the survival motor neuron 1 gene will develop SMA. The SMN protein that is normally encoded by the SMN1 gene is involved in the function of nerve cells that carry signals from the brain to move certain muscles. Although our bodies have another gene that produces SMN, the SMN2 gene — often called the SMA backup gene — it is not enough to make up for the loss of normal SMN1 gene function in individuals with SMA. The grant awarded to Hodgetts will be applied to the study of small molecules that can increase the amount of accumulated SMA protein produced by SMN2 to compensate for the loss of SMN1. This is expected to result in increased SMN protein in the brain and normalize the function of nerve cells that are affected in SMA. Hodgetts and his team have previously "identified lead compounds that increased SMN protein in brain and extended survival and motor function in a mouse model of SMA," Hodgetts said in an interview with Cure SMA. He said the SMA grant will help the teams to "continue the development of ... lead series of compounds, performing preclinical drug properties and toxicity studies, to ensure that they are as safe and effective as possible prior to entering clinical trials." The research funded by the grant will be carried out by Hodgetts and his team at the Laboratory for Drug Discovery in Neurodegeneration at Brigham and Women’s Hospital, an affiliate of Harvard Medical School, and Prof. Elliot Androphy and his team at Indiana University.

Either by coincidence or by design, MDA Hellas, the Muscular Dystrophy Association of Greece, is located on Elpidos Street in downtown Athens. Elpidos is Greek for “hope” — and that’s exactly what MDA Hellas offers the many neuromuscular disease patients under its care. Antigone Karras, executive manager of the…

Motor neuron death in patients with spinal muscular atrophy is related to abnormal RNA editing of two specific proteins, which leads to the activation of a key cell death pathway and neurodegeneration, a study suggests. Genes, which are composed of DNA sequences, are transcribed into molecules called RNA. In turn, RNA molecules are used as templates to make proteins, which carry out various functions in a cell. SMA is a neurodegenerative disease characterized by widespread RNA dysfunction, leading to the abnormal production of various proteins. RNA dysfunction in SMA patients is the result of a mutation in the gene that provides instructions to make the survival motor neuron protein, which is a major regulator of RNA splicing. RNA splicing is a process by which RNA molecules are edited to produce the final RNA product. When an RNA molecule is initially made, it is composed of alternating regions known as exons or introns. Through the use of RNA splicing, the intros of the RNA molecules are cut out and the exons are joined together. These exons are a vital part of the RNA molecule that actually contain the instructions used to make the protein. A deficiency in SMN leads to significant RNA dysfunction. One of the hallmarks of SMA is the progressive loss of spinal motor neurons, and researchers have been trying to understand the cause behind the excessive death of these motor neurons in patients. Studies using mouse models of SMA have shown that motor neuron death can be attributed to the p53-dependent pathway, which is activated by high levels of a protein called p53. The role of p53 in cells is to stop them from dividing and trigger the pathways that result in cell death. The molecular mechanisms that link a deficiency in the SMN protein to p53 activation and motor neuron death in SMA are currently unknown. Normally, p53 expression is kept at low levels in the cell by Mdm2 and Mdm4, proteins that negatively regulate p53. Therefore, researchers hypothesized that p53 activation in SMA involves a dysregulation of Mdm2 and Mdm4 due to abnormal RNA splicing caused by an SMN deficiency. Using both cellular and animal models, researchers in this study showed that a deficiency in the SMN protein “disrupts the balance between inclusion and exclusion of key regulatory exons in Mdm2 and Mdm4.” Specifically, they observed that exon 3 of Mdm2 and exon 7 of Mdm4 are not included in the final RNA molecules for these proteins in SMN-deficient cells. This dysfunction in RNA splicing activity causes problems in the biological activity of Mdm2 and Mdm4, and p53 becomes active. In fact, prior studies have shown that irregular RNA splicing of these specific exons is associated with an increase in p53 activity. Therefore, researchers conclude that their findings mechanistically link dysregulation of alternative splicing induced by SMN deficiency with motor neuron death, the key hallmark of SMA.