New approach for treating genetic muscle wasting disease shows promise in mice

March 6, 2012

New approach for treating genetic muscle wasting disease shows promise in mice | March 6, 2012

OTTAWA — Scientists from the Ottawa Hospital Research Institute (OHRI) and the University of Ottawa (uOttawa) have discovered that a drug called fasudil can extend the average lifespan of mice with Spinal muscular atrophy (SMA) from 30.5 days to more than 300 days.

The study is published today in BioMed Central’s open access journal BMC Medicine, by Dr. Rashmi Kothary, his graduate student Melissa Bowerman and others.

SMA is the leading inherited cause of death in infants and toddlers, affecting approximately 25,000 people in Canada and the United States. Scientists have known for many years that this disease is caused by inherited mutations in a gene called survival motor neuron 1 (SMN1). Most early attempts at developing treatments for SMA focused on replacing this gene, however, Dr. Kothary’s group has focused on understanding and targeting the physiological defects present in certain nerve cells with SMA. These cells have a weakened internal scaffold, which hinders their ability to connect with muscle cells and contributes to the severe muscle weakness associated with SMA.

Two years ago, Dr. Kothary and his team showed that a laboratory compound called Y-27632, which targets an enzyme that is involved in maintaining the cellular scaffold, could greatly increase lifespan in a certain mouse model of SMA. In this new study, they tested a compound called fasudil, which is similar to Y-27632, but has the advantage that it has already been approved for human clinical trials for other conditions, meaning that it could possibly be re-targeted to use in clinical trials for SMA more quickly than a completely new drug.

The Kothary group found that fasudil-treated SMA mice survived for an average of more than 300 days, compared to just 30.5 days for untreated SMA mice. However, the average lifespan of fasudil-treated SMA mice was still only about half as long as that of normal mice. Fasudil-treated SMA mice also had larger muscle fibres than the untreated SMA mice, and they behaved more normally with respect to grooming and other regular activities. However, they did not perform any better in strength and balance tests and they still had low numbers of motor neurons, which is typical for SMA.

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Child motor neurone disease treatment clue

February 27, 2012

Child motor neurone disease treatment clue

BBC News | February 26, 2012

Scottish research has shown it could be possible to reverse the muscle damage seen in children with a form of motor neurone disease.

Spinal muscular atrophy (SMA) – ‘floppy baby syndrome’ – is the leading genetic cause of death in children.

It affects one in 6,000 births, but 50% of those with the most severe form die before the age of two.

The University of Edinburgh mouse study suggests a drug could boost levels of a protein and so reverse muscle damage.

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SMA Gene Associated with Sporadic ALS

February 15, 2012

SMA Gene Associated with Sporadic ALS

MDA/ALS NewsMagazine | February 10, 2012 | By Amy Labbe

Duplications (extra copies) of the SMN1 gene are a “major” risk factor for developing sporadic (noninherited) ALS (amyotrophic lateral sclerosis), a team of scientists based in the Netherlands and United Kingdom has reported.

The SMN1 gene also is implicated in the motor neuron disease spinal muscular atrophy (SMA). Deletions or mutations in the SMN1 gene (SMN stands for “survival of motor neurons”) lead to a deficiency of SMN protein and are the underlying cause of SMA.

ALS and SMA both are diseases in which muscle-controlling nerve cells called motor neurons degenerate and die, leading to profound muscle weakness and, eventually, paralysis.

The research team, including corresponding author L.H. van den Berg at the University Medical Center Utrecht in Utrecht, the Netherlands, described its findings online Feb. 8, 2012, in Neurology. (See SMN1 gene duplications are associated with sporadic ALS.)

Further research is needed to determine how SMN1 gene duplications raise the risk of developing ALS, and any potential for SMN1-based ALS biological markers (biomarkers) or therapies.

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MDA Commits $12 Million to Neuromuscular Disease Research

February 1, 2012

MDA Commits $12 Million to Neuromuscular Disease Research

Quest Magazine | February 1, 2012 | By Amy Labbe

The Muscular Dystrophy Association has awarded 38 new grants totaling more than $12 million to fund research projects focused on its continuing mission to uncover the causes of, and develop therapies for, the more than 40 neuromuscular diseases in its program.

MDA’s Board of Directors reviewed and approved the new grants based on recommendations from the Association’s Scientific and Medical Advisory Committees, and the grants took effect Feb. 1.

Recent scientific advances have led to increased funding in promising new areas of research, including development of therapies that not only slow and stop neuromuscular diseases, but also reverse damage caused by the disease processes. The goal in many of the projects is to develop new therapies or to make current therapies better.

“It is exciting that several of these new basic research projects are focused on the development of new therapeutic strategies,” noted MDA Vice President of Research Sanjay Bidichandani.

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Newborn screening program aims to help transform treatments for genetic diseases detected at birth

January 17, 2012

Newborn screening program aims to help transform treatments for genetic diseases detected at birth

Press Release | January 17, 2012

Within the first days of life, screening tests are performed on all newborns born in the U.S. to identify rare and often life-threatening medical conditions that are not apparent at birth. These newborn screening programs have been operating for decades, permitting doctors to intervene early and improve outcomes in potentially devastating conditions.

Now a pediatric research project plans to strategically expand the data collection linked to newborn screening results, aiming to open up broad opportunities to develop new ways to screen for and treat childhood diseases.

Many existing therapies for rare childhood diseases are seriously limited, while screening tests and treatments remain to be discovered for many other congenital disorders not currently included in newborn screening. At The Children’s Hospital of Philadelphia, a research group is developing tools to store long-term clinical data on children with conditions picked up in the screening tests. The goal is to harness the power of numbers—using clinical data from many patients over years of their lives as a resource for researchers seeking new and better tests and treatments.

As biomedical knowledge and screening technology advance, more disorders have been added to those included in newborn screening, and the list will continue to grow.

“Currently, newborn screening programs are primarily limited to a short-term focus,” said project leader Peter S. White, M.D., director of the Center for Biomedical Informatics (CBMi) at The Children’s Hospital of Philadelphia. “The programs screen for disorders in which early intervention is possible. If we can broaden the data capture to follow up children over a longer term, we can tap the potential to develop new medical tests and interventions for diseases that are not currently detectable or treatable.”

Awarded this past October, the CBMi’s project, the Long-Term Follow-Up Data Collection Tool, is part of an ongoing five-year award from the Newborn Screening Translational Research Network (NBSTRN) to the American College of Medical Genetics. The NBSTRN, in turn, is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, part of the National Institutes of Health.

The subcontract award to Children’s Hospital totals $1.8 million over three years.

A classic example of a disease detected in newborn screening is phenylketonuria (PKU), in which a mutated gene disables a patient’s ability to process the amino acid phenylananine. Untreated, the excess amino acid causes severe mental retardation. But major diet restrictions, beginning in the first few weeks of life, allow near-normal development. Newborn screening programs have sharply reduced PKU-related mental retardation over the past four decades.

Over the years, more than 50 additional diseases have been added to the newborn screening list, including sickle cell disease and cystic fibrosis. If the initial screening flags a suspected disorder, healthcare providers order further tests to confirm or rule out the first result.

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Biogen Idec and Isis Pharmaceuticals Announce Global Collaboration for Antisense Program Targeting Spinal Muscular Atrophy

January 4, 2012

Biogen Idec and Isis Pharmaceuticals Announce Global Collaboration for Antisense Program Targeting Spinal Muscular Atrophy

Press Release | January 4, 2012

WESTON, Mass. & CARLSBAD, Calif., Jan 04, 2012 (BUSINESS WIRE) — — Biogen Idec’s Expertise in Neurology to Aid in Rapid Development of ISIS-SMNRx —

Biogen Idec BIIB +0.63% and Isis Pharmaceuticals, Inc. ISIS -0.28% today announced that they have entered into an exclusive, worldwide option and collaboration agreement under which the companies will develop and commercialize Isis’ antisense investigational drug, ISIS-SMNRx, for the treatment of spinal muscular atrophy (SMA).

SMA is a genetic neuromuscular disease characterized by muscle atrophy and weakness, and it is the most common genetic cause of infant mortality. One child out of every 10,000 births worldwide is born with SMA. Children with SMA generally appear normal at birth, with symptoms developing as early as a few months after birth, and in the most severe form of the disease, children have a significantly shortened lifespan. Isis’ ISIS-SMNRx is designed to compensate for the underlying genetic defect that causes SMA.

Under the terms of the agreement, Isis will receive an upfront payment of $29 million and is eligible to receive up to $45 million in milestone payments associated with the clinical development of ISIS-SMNRx prior to licensing. Biogen Idec has the option to license ISIS-SMNRx until completion of the first successful Phase 2/3 trial. Isis could receive up to another $225 million in a license fee and regulatory milestone payments. In addition, Isis will receive double-digit royalties on sales of ISIS-SMNRx. Isis will be responsible for global development of ISIS-SMNRx through the completion of Phase 2/3 registrational clinical trials, with Biogen Idec providing advice on the clinical trial design and regulatory strategy. If Biogen Idec exercises its option, it will assume global development, regulatory and commercialization responsibilities.

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BioTime to Produce Stem Cells for Research in Muscle Disorders

January 3, 2012

BioTime to Produce Stem Cells for Research in Muscle Disorders

Press Release | January 3, 2012

ALAMEDA, Calif., Jan 03, 2012 (BUSINESS WIRE) — BioTime, Inc. BTX +0.51% today announced that it has elected to market progenitors of muscle stem cells bearing hereditary diseases. BioTime will produce the products from five human embryonic stem (hES) cell lines from Reproductive Genetics Institute (RGI) of Chicago, Illinois. The muscle cell lines will display the genes for Duchenne muscular dystrophy, Emery-Dreifuss muscular dystrophy, spinal muscular atrophy Type I, facioscapulohumeral muscular dystrophy 1A, and Becker muscular dystrophy. The cell lines will be marketed researchers seeking new treatment modalities for these diseases.

“In the first quarter of this year, we will offer medical researchers normal muscle progenitor cell lines that we have already produced from BioTime’s existing hES cell lines, and later in 2012 we plan to add to our product line the novel muscle progenitor cells produced from RGI cell lines bearing the five genetic muscle diseases,” said Michael West, Ph.D., BioTime’s CEO. “BioTime’s business strategy includes generating near-term revenues in the emerging field of regenerative medicine by bringing some of the most advanced stem cell technologies to the market as research products.”

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Single Administration of Antisense Oligomer Delivered to the CNS Rescues a Severe Mouse Model of Spinal Muscular Atrophy

December 22, 2011

Single Administration of Antisense Oligomer Delivered to the CNS Rescues a Severe Mouse Model of Spinal Muscular Atrophy

FSMA News | December 22, 2011

The Burghes laboratory at Ohio State University publishes a paper in Human Molecular Genetics showing a single dose of an antisense oligomer (ASO) can greatly benefit survival, weight gain, and motor function in severe mouse model of SMA.

In this study, the authors delivered a bolus ICV injection of anti-sense oligonucleotide (ASO) of morpholino chemistry to alter SMN2 splicing and increase SMN levels. Treated SMA mice had improvement in weight gain, motor activity, and increased survival from 15 days to over 100 days. Delayed CNS delivery (P4) had an intermediate advantage, evidence that earlier CNS treatment yields more robust effects, while delayed peripheral delivery after blood-brain-barrier maturation had only modest increased survival. This suggests that CNS delivery of SMN is key to therapeutic benefit in this SMA mouse model.

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Isis Initiates Phase 1 Clinical Study of ISIS-SMNRx in Patients With Spinal Muscular Atrophy

December 19, 2011

Isis Initiates Phase 1 Clinical Study of ISIS-SMNRx in Patients With Spinal Muscular Atrophy

Press Release | December 19, 2011

CARLSBAD, Calif., Dec. 19, 2011 /PRNewswire/ — Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced today that it has initiated a Phase 1 study of ISIS-SMNRx in patients with spinal muscular atrophy (SMA). SMA is a severe motor-neuron disease that is the leading genetic cause of infant mortality. Isis is developing ISIS-SMNRx as a potential treatment for all Types of SMA.

“SMA is a devastating disease that leads to the loss of motor neurons resulting in muscle weakness and respiratory failure in children. The genetic cause of this disease is well understood, but there are currently no effective disease-modifying therapies. Currently, treatment of SMA is entirely symptomatic and focuses on preserving muscle strength and lung function by physical therapy and assisted ventilation. This supportive approach has improved the natural history of SMA by extending life expectancy, but muscle weakness and atrophy are not affected. A disease-modifying drug like ISIS-SMNRx that specifically targets the cause of the disease could, for the first time, restore muscle strength and respiratory function and dramatically improve the children’s function and quality of life,” said Darryl C. De Vivo, M.D., Sidney Carter Professor of Neurology and Pediatrics and Co-Director of the Motor Neuron Center at Columbia University Medical Center.

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theGSF and FightSMA Award $100,000 Spinal Muscular Atrophy Research Grant

December 16, 2011 | December 15, 2011

The Gwendolyn Strong Foundation (theGSF) and FightSMA are excited to announce a $100,000 award to Dr. Monique A. Lorson and University of Missouri in support of Dr. Lorson’s research focused on developing a large animal model of Spinal Muscular Atrophy (SMA).

Currently, no large animal model of SMA exists and the goal of Dr. Lorson’s research is to develop the first ever pig based model of SMA to be used by the broad, global SMA research community and other research groups to allow them to more efficiently and effectively move promising research from the bench to bedside. In short, this is a very exciting program that has the potential to have a material, positive impact on the future of SMA research in almost every category (e.g. gene therapy, compounds, antisense oligonucleotides).

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