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Administering stem cell therapy to the fetuses of mice with spinal muscular atrophy (SMA) type 3 improved the animals’ movement and survival after birth, a study reports. The research, “Prenatal transplantation of human amniotic fluid stem cells for spinal muscular atrophy,” appeared in the journal Current Opinion in Obstetrics and…

Heart defects occurring pre-birth may contribute to cardiac pathology in spinal muscular atrophy (SMA) patients, according to a mouse study. SMA patients primarily have loss of specialized nerve cells called motor neurons in the spinal cord, which causes progressive muscle atrophy. However, patients also may develop impairments in the liver, lungs, pancreas, spleen, testis, gut, and blood vessels. Cardiac abnormalities long have been associated with SMA, but only recently have they been recognized as a core feature of severe SMA. These are divided in two major categories: structural defects, and arrhythmia (irregular heartbeat). The most common congenital structural defects in SMA patients are in the atrial and ventricular septum, which refers to the wall dividing the left and right parts of the heart, and in the aortic arch — the artery's intersection between ascending and descending zones. However, pulmonary hypertension, ventricular enlargement, and cardiomyopathies — disorders of the heart’s muscle — also have been described. Altogether, the evidence suggests a diverse array of cardiac defects, which warrants further research to clarify the exact involvement of these co-morbidities in SMA. Mouse models of both mild and severe SMA have successfully reproduced the complex picture of cardiac defects, but their understanding is still incomplete. Besides heart defects, reduced blood vessel density, necrosis and the formation of blood cells outside of the bone marrow — are further cardiovascular system impairments in SMA.  These abnormalities have been observed in both patients and mouse models with severe disease. The research team conducted a detailed morphological analysis of the heart in the Taiwanese mouse model used to replicate a severe phenotype of SMA, and focused on the period between birth and the first appearance of neuromuscular symptoms to identify the mechanisms underlying the initiation of cardiovascular defects. The analysis revealed thinning of the ventricular septum at three days after birth and dilation of the ventricles at pre- and early-symptomatic ages, which matched data from other mouse models. Importantly, researchers observed that the thinning of the left ventricular wall occurred from birth, prior to any neuromuscular symptoms. Changes in the collagen IV protein also occurred from birth and contributed to abnormal arrangement of cardiomyocytes — cells that make up the heart’s muscle. These cells also exhibited oxidative stress before symptom's initiation and increased apoptosis (cell death) during the early stages of SMA. In addition, the heart’s vascular density was decreased. Importantly, researchers observed increased blood retention in the hearts of the mice, suggesting functional defects. “Taken together, these findings point toward impaired development of the SMA heart as a significant contributor to cardiovascular defects,” researchers wrote. "These pathologies mirror dilated cardiomyopathy, with clear consequences for heart function that would likely contribute to potential heart failure.” The team believes its findings support the need to develop disease therapies that also target non-neuromuscular alterations in SMA patients.

Levels of a male hormone produced by the adrenal glands could provide useful information on the severity of spinal and bulbar muscular atrophy, or SBMA, a study reports. The identified the hormone as DHEA sulfate. Researchers’ study, published in the Journal of Neurology, is titled “The metabolic…

Using an advanced imaging technique and complex computational algorithms, researchers have created the first detailed, 3D imaging of a group of proteins called dyneins that may lead to a better understanding of the underlying causes of spinal muscular atrophy (SMA) and other neurodegenerative diseases. Dyneins play a…

Retrophin and the U.S. subsidiary of Britain’s Horizon Pharma will each donate $3 million over a six-year period to the Rare Disease Institute (RDI) at Children’s National Health System in Washington, D.C., helping it to strengthen care available and expand as a “center of excellence” for rare…

In recognition of Rare Disease Day 2018, Bionews Services — which publishes this website — will attend and report on three relevant conferences in the U.S. dealing with policies and programs of importance to patients and their families. The three are among 50 events in 32 states…

The National Network for Excellence in Neuroscience Clinical Trials  is accelerating the clinical trial process for neurological diseases like spinal muscular atrophy with the expectation of bringing medications to market in less time, with fewer costs and less risks. Clinical studies for neurological diseases are typically long and arduous, taking many years and a lot of money to complete. As such, developing medications to treat these conditions also is long and expensive. With funding from the National Institutes of Health , and leadership from the University of Iowa, NeuroNEXT is a consortium that brings together 25 academic healthcare research institutions nationwide to facilitate and diminish costs associated with clinical trials for neurological diseases. The consortium is designed to facilitate patient recruitment, help control quality and methodological standardization across studies and to assist data-gathering in the most efficient and cost-effective way possible, which already facilitates cross-referencing and comparability of results. The consortium was funded in 2011, but results of its first trial weren't published until December 2017, in Annals of Neurology, which is a large time gap that illustrates just how much time it can take to study neurological diseases. The two-year study, “Natural history of infantile-onset spinal muscular atrophy,” led by researchers at the Ohio State University observed biomarkers that indicate infantile-onset SMA. The trial involved researchers at 15 NeuroNEXT sites and the data collected were used to inform the U.S. Food and Drug Administration (FDA) application for the approval of Spinraza (nusinersen). Looking at the natural history of 26 SMA infants and 27 controls, the data delineated meaningful change in clinical trials in infantile-onset SMA, demonstrating the power and utility of NeuroNEXT to provide “real-world,” prospective natural history data sets and accelerate public and private drug development programs for rare diseases. The gene therapy AVXS-101, being developed by AveXis for SMA, is currently in clinical trials and soon may be available, too. Ultimately the goal is to encourage more clinical trials in neurological disorders, see those trials through to completion, and ascertain if there is enough promise to go forward in drug development. NeuroNEXT focuses exclusively on Phase 2 studies, which means researchers are not looking for a definitive answer to whether a treatment is effective, but are instead seeking to learn more about a potential treatment to decide whether there is enough evidence to justify the cost and complexity of a larger, more definitive Phase 3 trial.

Scientists have discovered a new way to more efficiently deliver lower doses of gene therapies, and overcome adverse side effects that can be caused by high treatment dosages, a study suggests. The study, “Mapping the Structural Determinants Required for AAVrh.10 Transport across the Blood-Brain Barrier,” was published in the…

A rock-painting contest in Las Vegas. A fashion show in New York. A 7,000-meter race around the Washington Monument that’ll coincide with a similar #Racefor7 event in Bengaluru and Mumbai, India. From Athens to Atlanta, from San Diego to Sydney, people across the globe will mark World Rare Disease…

Approval of Spinraza (nusinersen), the first disease-modifying therapy for spinal muscular atrophy (SMA), has brought not only hope, but also some challenges for both patients and researchers, according to a recent review. The study, “Advances in therapy for spinal muscular atrophy: promises and challenges,” was published…