The RASCALS Foundation Announces Higher Education Scholarships for 2014

blue tassel

The RASCALS Foundation is pleased to announce that it is once again offering  the 2014 Higher Education Scholarship Program to assist families affected by ALS. We would like to acknowledge and thank our newest partner Helping Hands for ALS, a student group associated with John Burroughs High School for their generous participation in making these important awards possible.

The scholarships will be available nationwide to the first 100 qualifying applicants. The program, guidelines and application process will begin today, March 20, 2014. To request an application packet, simply email MichaelBrand314@gmail.com  or call 314-477-8120.

You may also check the website  for guideline information to be posted in a dedicated 2014 Scholarship section.

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The Robert A. Stehlin Campaign for ALS (R.A.S.C.A.L.S.) is an all-volunteer 501(c)(3) charity. 100% of all funds raised go to building awareness, treatment research and development, plus ALS family assistance. There are no administrative costs.

Contributions are tax-deductible.

You may also be interested in visiting the RASCALS Store.

The material presented here is for informational purposes only and should not be construed as medical advice, or relied upon as a substitute for medical advice from a health care provider.

ALS Toxicity Reduced in Animal Models

Amyotrophic lateral sclerosis (ALS), better known as Lou Gehrig’s disease, is a devastating illness that gradually robs sufferers of muscle strength and eventually causes a lethal, full-body paralysis. The only drug available to treat the disease extends life spans by a meager three months on average.

In a new study published in Nature Genetics, University of Pennsylvania researchers and colleagues have made inroads into the mechanism by which ALS acts. Working with a powerful fruit fly model of the disease, they found a way of reducing disease toxicity that slows the dysfunction of neurons and showing that a parallel mechanism can reduce toxicity in mammalian cells. Their discoveries offer the possibility of a new strategy for treating ALS.

The senior author of the study is Nancy Bonini, a professor in the Department of Biology in Penn’s School of Arts and Sciences. Contributors from her lab include Hyung-Jun Kim, Leeanne McGurk and Ross Weber. They partnered on the work with long-time collaborators from Penn’s Perelman School of Medicine, John Trojanowski and Virginia M-Y Lee. Additional co-authors included Alya Raphael and Aaron Gitler of Stanford University and Eva S. LaDow and Steven Finkbeiner of the Gladstone Institute of Neurological Disease.

Recent years have seen an uptick in scientific understanding of the genetic roots of ALS.

“There’s been an explosion over the last five-plus years in the identification of genes that contribute to genetically inherited ALS,” Bonini said.

One of the key genes that has come to light as playing a role in the disease is called TDP-43, which binds to RNA and has been found to aggregate abnormally in the cytoplasm of patients with ALS.

Previous studies led by Gitler and Bonini, working with colleagues including Trojanowski and Lee, had found that TDP-43 interacts with a gene called ataxin-2.

“That became very interesting to us because ataxin-2 on its own is a gene whose mutations cause human degenerative disease,” Bonini said.

Given the strong interactions between TDP-43 and ataxin-2, and additional findings of an association of ataxin-2 with ALS, the team continued investigating this interaction. Bonini’s lab has long pursued questions about neurodegenerative disease using the fruit fly as an animal model and did so again in this work.

“These model systems are very fast and simpler than mammalian models,” Bonini said. “They allow us to focus on conserved pathways and can be remarkably powerful for giving us insight into pathways involved in disease.”

Using yeast models and the fly, the team showed that genes that modulate cellular structures known as stress granules, which act as holding pens for RNA and proteins when cells are under stress, modify TDP-43 toxicity. Previous work had suggested that ALS patients may have abnormal accumulations of stress granule components, indicating that the structures might somehow be tied to the disease. In flies, the Bonini team found that expression of genes predicted to promote stress granules increased the toxic activity of TDP-43 in genetic screens, underlining the importance of these structures to the pathology of ALS.

Investigating fruit flies engineered to express the human version of TDP-43, they found the flies showed signs of a build-up of stress granule components, as evidenced by an increase in the tagging of a molecule called eIF2-alpha with a phosphate group. eIF2-alpha phosphorylation is associated with formation of stress granules and reduced generation, or translation, of proteins. These flies also had symptoms reflective of ALS; they could not climb as readily as normal flies and had shorter lifespans.

The researchers were able to modulate these symptoms, however, by altering the expression of genes related to eIF2-alpha phosphorylation and stress granules.

From the Editors at Bioscience Technology, December 17, 2013 •

Further, using transgenic flies, the team identified a region of the ataxin-2 protein critical for increasing the detrimental effects of TDP-43. That region is known to be a binding site of a protein called poly-A binding protein, or PABP, that is also known to go to stress granules.

“If you knock out that domain, there is a dramatically reduced interaction between TDP-43 and ataxin-2,” Bonini said. “That, coupled with our other data, is suggestive of the idea that the disease state may be associated with pathological stress granules. Perhaps they are remaining in the cell too long or not being resolved properly.”

As in the flies, PABP may factor into human disease, the researchers found. Examining ALS patients’ spinal cord tissue, they found dense aggregations of PABP in the cytoplasm, reminiscent of stress granules.

Finally, the researchers went back to the fly to see if they could reverse the TDP-43 toxicity.

They fed flies a compound developed by GlaxoSmithKline that inhibits the addition of phosphate groups to eIF2-alpha. Reducing eIF2-alpha phosphorylation is predicted to mitigate stress granule formation and the state of translational repression associated with stress granules. Upon feeding flies, they witnessed a dramatic restoration of physical strength in the flies expressing TDP-43. Those fed the compound retained more climbing ability compared with animals without the compound.

To test the effectiveness of the GSK compound in mammalian cells, the team exposed rat neuron cells expressing TD-43 in culture to the compound, and found it reduced the risk of cell death. The data raise the possibility that the prolonged stress state associated with stress granules and the deleterious effects on cellular pathways associated with such prolonged stress are important in disease.

Bonini suggests the results show promise for a treatment strategy for ALS and highlight again the power that flies, yeast and other seemingly simple model organisms can have in shedding light on human neurological disease.

“We can integrate from a number of extraordinarily powerful systems, including yeast, fly and then mammalian cell culture, to see if, with this united front, we can provide evidence from all spokes that the approach is suggestive of a therapeutic effect,” she said. “They are all important pieces of the puzzle.”

Source: University of Pennsylvania

Biomarkers Help Predict Progress of ALS

Researchers from Penn State Hershey ALS Clinic and Research Center are joined by University of Washington Medical Center for Study

Analysis shows that looking at multiple biomarkers to predict the progression of amyotrophic lateral sclerosis, commonly known as Lou Gehrig’s disease, is not only mathematically possible, it improves upon methods using single biomarkers. (Credit: Christopher "Rice"/Flickr)

Analysis shows that looking at multiple biomarkers to predict the progression of amyotrophic lateral sclerosis, commonly known as Lou Gehrig’s disease, is not only mathematically possible, it improves upon methods using single biomarkers.
(Credit: Christopher “Rice”/Flickr)

By for Penn State

Measuring changes in certain proteins—called biomarkers—in people with amyotrophic lateral sclerosis (ALS) may be a better way to predict progression of the disease. ALS, often referred to as Lou Gehrig’s disease, is a neurological disease in which the brain loses its ability to control movement as motor neurons degenerate. The course of the disease varies, with survival ranging from months to decades.

“The cause of most cases of ALS remains unknown,” says James Connor, distinguished professor of neurosurgery, neural and behavioral sciences and pediatrics at Penn State.

“Although several genetic and environmental factors have been identified, each accounts for only a fraction of the total cases of ALS.” This clinical variation in patients presents challenges in terms of managing the disease and developing new treatments. Finding relevant biomarkers, which are objective measures that reflect changes in biological processes or reactions to treatments, may help address these challenges.

Multiple ALS biomarkers

For the study, researchers studied plasma and cerebrospinal fluid samples previously collected from patients undergoing diagnostic evaluation, who were later identified as having ALS.

Analysis shows that looking at multiple biomarkers to predict progression is not only mathematically possible, it improves upon methods using single biomarkers.

Statistical models analyzing plasma had reasonable ability to predict total disease duration and used seven relevant biomarkers.

For example, higher levels of the protein IL-10 predict a longer disease duration. IL-10 is involved with anti-inflammation, suggesting that lower levels of inflammation are associated with a longer disease duration.

Researchers identified six biomarkers for cerebrospinal fluid. For example, higher levels of G-CSF—a growth factor known to have protective effects on motor neurons, the cells that die in ALS—predicts a longer disease duration.

Perhaps most importantly, the results suggest that a combination of biomarkers from both plasma and cerebrospinal fluid better predict disease duration.

While the size of this study is small, the ability of the specific biomarkers used to predict prognosis suggests that the approach holds promise.

“The results argue for the usefulness of researching this approach for ALS both in terms of predicting disease progression and in terms of determining the impact of therapeutic strategies,” Connor says.

“The results present a compelling starting point for the use of this method in larger studies and provide insights for novel therapeutic targets.”

Xiaowei Su, an graduate student in Connor’s laboratory, led the study in collaboration with Zachary Simmons, director of the Penn State Hershey ALS Clinic and Research Center. Researchers from the University of Washington Medical Center also contributed.

The Paul and Harriett Campbell Fund for ALS Research, the Zimmerman Family Love Fund, and the ALS Foundation, Philadelphia chapter, provided funding for the research.

Source: Penn State

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The Robert A. Stehlin Campaign for ALS (R.A.S.C.A.L.S.) is an all-volunteer 501(c)(3) charity. 100% of all funds raised go to building awareness, treatment research and development, plus ALS family assistance. There are no administrative costs.

Contributions are tax-deductible.

You may also be interested in visiting the RASCALS Store.

The material presented here is for informational purposes only and should not be construed as medical advice, or relied upon as a substitute for medical advice from a health care provider.

ALS Takes a Deep Breath with Diaphragmatic Pacing System

From the Ivanhoe Newswire

COLUMBUS, Ohio (December 19, 2013)  — ALS, also known as Lou Gehrig’s disease, is a progressive neuro-degenerative disease that affects nerve cells in the brain and spinal cord. Sooner or later, it will attack every muscle in a patient’s body, making it impossible to move, even breathe. Now, a new machine is helping people suffering from ALS breathe easier.
Mary Pat Murray has lived with ALS for more than four years. Checkups are not just routine for her, they can be lifesaving.

Traditionally, patients like Mary would use a BiPAP machine to help her breathe. She’d wear a mask, tethered to a ventilator. It would force air into Mary’s lungs.

Now, Mary is the first ALS patient at The Ohio State University to be implanted with a diaphragmatic pacing system to help her strengthen her muscles.

“It feels like a really hard hiccup at first and then eventually you get used to it,” Mary told Ivanhoe.

The external device sends electrical signals to the nerve that controls the diaphragm, replacing signals normally sent by the brain telling it to expand and retract.

“All she needs to do when she is ready at night is to turn that on and it’ll begin to help to contract the diaphragm as she’s breathing,” Stephen J. Kolb, MD, PhD, Co-Director, ALS/MND Clinic, Department of Neurology, The Ohio State University Wexner Medical Center, told Ivanhoe.

The DPS conditions the muscle while Mary sleeps.

“This gives us another tool in our tool belt where we can maybe engage the motor-neurons in the diaphragm; maybe allow the diaphragm to maintain strength longer in ALS, and improve quality of life and lifespan, so it’s very exciting,” Dr. Kolb said.

In just six months, Mary says she’s felt a difference.

“I can carry on a conversation. I can eat. I can drink,” Mary explained.

She is thankful for the technology that allows her to do what most of us take for granted.

Thirty thousand Americans are living with ALS right now. Next year the device will be part of a multi-clinic study to determine if DPS actually helps ALS patients live longer in addition to breathing easier.

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The Robert A. Stehlin Campaign for ALS (R.A.S.C.A.L.S.) is an all-volunteer 501(c)(3) charity. 100% of all funds raised go to building awareness, treatment research and development, plus ALS family assistance. There are no administrative costs.

Contributions are tax-deductible.

You may also be interested in visiting the RASCALS Store.

The material presented here is for informational purposes only and should not be construed as medical advice, or relied upon as a substitute for medical advice from a health care provider.

New Gene Variant Discovered for ALS

dna_helixLeadArtFrom the Editors at Medical Xpress, December 3, 2013 •

Research led by King’s College London has identified a new genetic variant, located on chromosome 17, associated with sporadic amyotrophic lateral sclerosis (ALS) – the most common form of motor neurone disease (MND).

With genetic data from over 17,000 individuals, the study is the largest of its kind and provides a new insight into the genetic structure of the disease.

ALS is a neurodegenerative disease which causes progressive muscle paralysis and is fatal within 3-5 years. Around 10 per cent of cases run in families, with the remainder occurring sporadically. Previous studies have identified a number of genetic variants associated with familial ALS, but for non-familial, or sporadic, ALS, only a gene on chromosome 9 has been identified.

The new study, published in Human Molecular Genetics, is the result of a large international collaboration led by scientists at the Institute of Psychiatry at King’s, in collaboration with universities in the UK, Italy, USA, Germany, Netherlands and France, and is the largest genome wide association study (GWAS) for ALS to date.

A total of 13,225 individuals (6,100 cases and 7,125 controls) were analysed for almost 7 million genetic variants. This included 3,959 newly genotyped Italian individuals (1,982 cases of ALS and 1,977 controls) combined with published genotype data from the Netherlands, USA, UK, Sweden, Belgium, France, Ireland and Italy.

The researchers identified a novel variant on chromosome 17 associated with ALS risk (17q11.2) and confirmed the association with the previously reported gene on chromosome 9 (9p21.2). The association on chromosome 17 was then confirmed in an independent set of 4,656 individuals.

The researchers estimate for the first time that the contribution of common to non-familial ALS is approximately 12%. The newly identified genetic variant on chromosome 17 is closely linked to a gene (SARM1) known to play a key role in axon, or nerve fibre death. The authors add that this new finding may lead to the discovery of new pathways involved in ALS, indicating potential new drug targets.

Dr Isabella Fogh and Dr John Powell from the Department of Neuroscience at the Institute of Psychiatry at King’s are co-authors of the study.

Dr Fogh says: “This is really exciting work. Whilst there have been a number of genes identified in familial ALS, very few have been identified in sporadic ALS, even though this form of the disease accounts for 90% of cases. Multiple genetic and environmental factors are implicated in the development of this devastating disorder. What we have here is another key part of the puzzle.”

More information: Isabella Fogh et al. ‘A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis’ Human Molecular Genetics hmg.oxfordjournals.org/content/early/2013/11/20/hmg.ddt587.full.pdf

Journal reference: Human Molecular Genetics search and more info website

Provided by King’s College London

New Device Delays Ventilator Need for Some ALS Patients (Op-Ed)

By Dr. Stephen Kolb for Live Science, December 3, 2013 •

For patients with amyotrophic lateral sclerosis (ALS), the simple act of breathing is often a tough thing to do. Now, these patients have new hope, as a device has been approved by the U.S. Food and Drug Administration (FDA) that may help patients to breathe more easily without a ventilator.

lungs-diagram-120926ALS, also known as Lou Gehrig’s disease, is a rapidly progressing, incurable and fatal neuromuscular disease characterized by progressive muscle weakness that results in paralysis. For ALS patients, diaphragm weakness contributes significantly to respiratory insufficiency, and ultimately respiratory failure, which is the most common cause of death for these patients. As the phrenic nerve to the diaphragm muscle fails, patients lose the ability to breathe without ventilator support.

Approximately 30,000 people in the United States live with ALS. More than 5,600 new cases are diagnosed each year, and about 3,300 of those patients might benefit from a diaphragmatic pacing system (DPS).

I recently worked with my colleague, Dr. Patrick Ross, a thoracic surgeon at The Ohio State University Wexner Medical Center to implant the NeuRx DPS device in Mary Pat Murry of London, Ohio. Our integrated ALS clinic and surgical center is the first to offer this new device to patients in Ohio, Kentucky and Indiana. We are one of only 30 integrated, multidisciplinary ALS clinics nationwide currently offering the device.

The device provides electrical stimulation to the nerve that innervates the diaphragm, similar to how a cardiac pacemaker works to stimulate the heart. When the device stimulates the nerve, the diaphragm contracts, and this helps condition the muscle to improve fatigue resistance during normal exertion.

Most ALS patients develop chronic hypoventilation over the course of their disease. Traditionally, we assist them with non-invasive ventilator support. The hope is that the diaphragmatic pacing system will help patients breathe for a longer period without needing a ventilator.

The DPS treatment is working well for Murry, whose respiratory function initially increased and has now plateaued, instead of continuing to decline. She tells me she feels more rested and has more energy since she has been using the DPS about 10 hours a day.

In 2014, Ohio State will participate in a national multi-center clinical trial that will try to determine if DPS treatment for patients with ALS and hypoventilation will improve survival or diaphragm function. About 20 Northeast ALS Consortium (NEALS) centers in the United States will participate in the randomized study that will enroll 180 patients. Study participants will be randomly assigned in a 2:1 ratio to DPS or standard-of-care treatment groups.

In an earlier multi-center clinical trial, the device was approved by the FDA under a Humanitarian Device Exemption marketing approval, based on demonstration of safety and probable benefit, including the likelihood that it will help ALS patients live longer and sleep better than the current standard of care. The device is controlled through a four-channel, battery-powered, external pulse generator.

The NeuRx DPS was developed over 20 years through a joint effort of physicians and engineers at several institutions.

ALS is incurable and right now physicians can’t stop its progress, but we are optimistic that this will give people with ALS a better quality of life during the course of their disease.

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Dr. Stephen Kolb, a neurologist at The Ohio State University Wexner Medical Center, contributed this article to LiveScience’s Expert Voices: Op-Ed & Insights.

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The Robert A. Stehlin Campaign for ALS (R.A.S.C.A.L.S.) is an all-volunteer 501(c)(3) charity. 100% of all funds raised go to building awareness, treatment research and development, plus ALS family assistance. There are no administrative costs.

Contributions are tax-deductible.

You may also be interested in visiting the RASCALS Store.

The material presented here is for informational purposes only and should not be construed as medical advice, or relied upon as a substitute for medical advice from a health care provider.

Diaphragm Pacing System Benefits Patients With ALS

From the editors of Science Daily, Oct. 17, 2013 •

Respiratory failure is one of the major complications associated with amyotrophic lateral sclerosis (ALS). The quest for alternative approaches for treating respiratory failure has led to the study, and subsequent FDA approval, of diaphragm pacing for use in ALS patients. However, there are still important unanswered questions about its benefit and impact.

In a study presented at the annual meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM), the outcomes of 28 of 34 ALS patients with diaphragm pacing systems (DPS) were analyzed for up to 14 months after implantation. All patients also used a bi-level positive airway pressure (BiPAP) portable ventilator after DPS implantation. More than 50% of the patients reduced their use of BiPAP during the first 3-4 months after implantation and had slower declines in respiratory function. Overall, the researchers found that diaphragm pacing resulted in improved quality of life, with better sleep and daytime functioning, better breathing, and less fatigue.

“This study presents important positive results at one-year of follow-up that support the use of diaphragm pacing as an additional strategy to manage respiratory failure in patients with ALS,” said Carlos Luciano, MD, AANEM News Science Editorial Board member.

“The data also confirms previously published results suggesting that diaphragm pacing improves sleep in ALS patients.”

SOURCE: The above story is based on materials provided by American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM), via Newswise.

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The Robert A. Stehlin Campaign for ALS (R.A.S.C.A.L.S.) is an all-volunteer 501(c)(3) charity. 100% of all funds raised go to building awareness, treatment research and development, plus ALS family assistance. There are no administrative costs.

Contributions are tax-deductible.

You may also be interested in visiting the RASCALS Store.

The material presented here is for informational purposes only and should not be construed as medical advice, or relied upon as a substitute for medical advice from a health care provider.

ImStar Selects Lead ALS Drug Candidate for Study by Mid-2014

VANCOUVER, November 30, 2013  ImStar Therapeutics, a private biotechnology company developing a new approach to treat patients with ALS, has selected IMS-088 as its lead drug candidate for the treatment of Amyotrophic Lateral Sclerosis (ALS). The company is preparing to initiate IND-enabling studies in the second half of 2014.

IMS-088 is a novel, small-molecule drug that stems from the discovery of a new target for ALS by ImStar co-founder Dr Jean-Pierre Julien termed TANA (i.e. TDP-43 Associated NF-kB Activation). IMS-088 is the first in a series of novel drugs derived from withaferin A, a natural compound isolated from the leaves of the winter cherry plant (Withania somnifera) that inhibits activation of a key inflammation pathway. In preclinical ALS disease models, withaferin A produced substantial improvements in function and extended survival, but lacked optimal characteristics to be developed as a drug. IMS-088 was designed by ImStar chemists to have superior drug-like properties and has been shown to be potent and safe in preclinical studies.

In conjunction with the selection of a lead compound, ImStar has filed a patent application with the United States Patent and Trademark Office covering novel withanolide therapeutics.

“We are very excited to announce the selection of IMS-088 as ImStar’s lead ALS compound. As we continue with preclinical development next year, we hope to establish IMS-088 as a safe and effective new drug candidate for ALS,” said Jean-Pierre Julien, ImStar’s chief scientific officer. “This is an important milestone for ImStar,” said Daniel Wattier, CEO of ImStar, “It reflects our commitment to transforming this important discovery into a practical treatment for patients.”

Amyotrophic Lateral Sclerosis (ALS), commonly known as “Lou Gehrig’s disease”, is a progressive neurodegenerative disease that inhibits an individual’s ability to control voluntary muscle movement. ALS leads to paralysis and death in most cases.

SOURCE: PharmaBiz.com

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The Robert A. Stehlin Campaign for ALS (R.A.S.C.A.L.S.) is an all-volunteer 501(c)(3) charity. 100% of all funds raised go to building awareness, treatment research and development, plus ALS family assistance. There are no administrative costs.

Contributions are tax-deductible.

You may also be interested in visiting the RASCALS Store.

The material presented here is for informational purposes only and should not be construed as medical advice, or relied upon as a substitute for medical advice from a health care provider.

 

Neuraltus’ NP001 Phase 2 Results Highlighted at 24th International Symposium on ALS/MND

Findings Show Positive Trends in Slowing Advancement of Disease, as well as Enhanced Activity of NP001 in Patients with Increased Baseline Inflammation; Phase III expected in 2014

PALO ALTO, California, December 9, 2013 — Neuraltus Pharmaceuticals, Inc. announced today that promising efficacy results of the Company’s Phase 2 clinical program of NP001 for the treatment of amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease) were highlighted in an oral presentation at the 24th International Symposium on ALS/MND, held in Milan, Italy.  Study efficacy results demonstrated positive trends in the ability of NP001 to slow the rate of disease progression, ranging from 13 to 19% in multiple parameters of clinical benefit, although these pre-defined endpoints did not reach statistical significance.  According to a post hoc analysis, a greater percentage of patients receiving NP001 experienced a halt in disease progression which reached statistical significance when compared to the combination of concurrent and matched historical (placebo) controls.  The high dose of NP001 (2mg/kg) halted progression in 27% of patients compared to 11% of patients on placebo.  Further, NP001 was found to be safe and well-tolerated in the study.

In addition, the researchers discovered a trend in greater improvement in patients with higher baseline inflammation who received the high dose of NP001, achieving a 44% improvement compared to placebo.  These findings provide further support for the hypothesis that NP001′s primary mechanism of action is the restoration of normal function in inflammatory macrophages.  The Phase 2 data were reported in an oral presentation, titled “Additional Follow-up and Biomarker Data from a Phase II Safety and Preliminary Efficacy Trial of NP001: A Novel Immune Regulator for Slowing Progression of ALS,” delivered by Principal Investigator Robert G. Miller, MD, who serves as Director of the Forbes Norris MDA/ALS Research and Treatment Center of the California Pacific Medical Center.

NP001 is a small molecule regulator of inflammatory macrophage activity.  Aberrant macrophage activity is believed to be a significant contributor to the pathology underlying ALS and other neurodegenerative diseases.  Neuraltus’ NP001 is designed to restore the normal functioning of macrophages within the central nervous system.

According to Dr. Miller, “We are pleased to report the current, most up-to-date findings from the Phase 2 study.  Clinical effects of NP001 are consistent with what we’ve seen in earlier research, which demonstrated that NP001 is able to lower markers of abnormal inflammatory macrophages in in vitro and in vivo preclinical studies, as well as in a dose-dependent manner in earlier-stage clinical work.  In the Phase 2 study, we saw a halting of disease progression in 27% of the high-dose treatment group patients, a finding we have never seen in prior ALS trials.  In addition, we strongly believe the trial design confirmed the utility of using historical placebo controls for signal amplification and hypothesis generation and that the benefit-risk supports further development of NP001.  We look forward to the continued progress of this program.”

Neuraltus recently updated their development timeline for NP001, noting that the Company is expecting to initiate a Phase 3 study sometime in 2014.

More About the Phase 2 NP001 Study

The multi-center, double-blind, placebo-controlled, Phase 2 study enrolled 136 patients with ALS. Patients were randomized to receive either placebo, or 1mg/kg or 2mg/kg intravenous infusion of NP001 over a period of six months, followed by a six-month follow-up period. The study was designed to evaluate the change in slope of the ALS Functional Rating Score Revised (ALSFRS-R) and the safety and tolerability of NP001, as well as change from baseline in ALSFRS-R through six months, a joint rank analysis of change of ALSFRS-R adjusted for mortality and changes in readily measured peripheral inflammation biomarkers. An additional secondary endpoint agreed upon with the FDA was the inclusion of matched historical placebo control ALS patients to increase signal detection and power.

Post hoc analysis of the Phase 2 study showed a dose response to NP001 with 27% of the patients who received 2mg/kg NP001 having no progression of their disease during the six-month dosing period. This is approximately 2.5 times as many as were seen in the concurrent placebo group. When historical placebo controls were included with concurrent controls, this difference versus placebo became statistically significant. Although post hoc analysis must be considered cautiously and can be subject to bias, the magnitude of the benefit identified underscores a potentially clinically relevant and meaningful result. In addition, results from the study demonstrated trends of clinical benefit for the 2 mg/kg cohort in the primary endpoint of change in slope of the ALSFRS-R, and in the secondary endpoints of change from baseline in ALSFRS-R through six months and a joint rank analysis of change of ALSFRS-R adjusted for mortality.  Further, the benefit of NP001 related to the degree of baseline inflammation in patients.  Those patients with greater baseline inflammation and who received the high dose of NP001 experienced a 44% greater slope improvement (positive trend did not reach significance, however).

About Neuraltus Pharmaceuticals, Inc.

Neuraltus Pharmaceuticals, Inc. is a privately-held biopharmaceutical company developing novel therapeutics to treat neurological disorders. Neuraltus’ clinical-stage product candidate, NP001, has been shown to regulate the activation of select immune cells (macrophages), transforming them from an activated or inflammatory state to their normal quiescent state in order to normalize the cellular environment of critical nerve cells. Neuraltus has completed a Phase 2 clinical study of NP001 in patients with amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease), results of which were reported in late 2012.

For more information on Neuraltus, please visit www.neuraltus.com.

CONTACT: 

Rich Casey, President and CEO, Neuraltus Pharmaceuticals, Inc.
Tel: (650) 424-1600 x. 300
Email: rcasey@neuraltus.com

Burns McClellan, on behalf of Neuraltus
Justin Jackson (media)
jjackson@burnsmc.com

SOURCE: Neuraltus Pharmaceuticals, Inc.

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The Robert A. Stehlin Campaign for ALS (R.A.S.C.A.L.S.) is an all-volunteer 501(c)(3) charity. 100% of all funds raised go to building awareness, treatment research and development, plus ALS family assistance. There are no administrative costs.

Contributions are tax-deductible.

You may also be interested in visiting the RASCALS Store.

The material presented here is for informational purposes only and should not be construed as medical advice, or relied upon as a substitute for medical advice from a health care provider.

Cytokinetics to Present BENEFIT-ALS Trial Insights at International Symposium

South San Francisco, California, December 2, 2013 – Cytokinetics announced today that a presentation relating to tirasemtiv and BENEFIT-ALS, is scheduled to be presented at the 24th International Symposium on ALS/MND to be held December 6-8, 2013 at the Atahotel Quark in Milan, Italy.

The presentation will elaborate on the clinical trial design and include enrollment and baseline demographics data from BENEFIT-ALS (Blinded Evaluation of Neuromuscular Effects and Functional Improvement with Tirasemtiv in ALS), which is evaluating tirasemtiv, a novel mechanism skeletal muscle activator, as a potential treatment for patients with amyotrophic lateral sclerosis (ALS).

Platform Presentation at the 24th International Symposium on ALS/MND

Date:   Saturday, December 7, 2013
Location:  Atahotel Quark, Aquarium Room
Presentation Time:  4:00 PM – 4:15 PM (Central European Time)
Session:  8B – Clinical Trials and Trial Design
Title:  The Effect of Tirasemtiv on Functional Status in Patients with ALS
Presenter:  Jeffrey M. Shefner, M.D., Ph.D., Professor and Chair, Department of Neurology at the Upstate Medical University, State University of New York

About Tirasemtiv and BENEFIT-ALS

Tirasemtiv, a novel skeletal muscle activator, is the lead drug candidate from the company’s skeletal muscle contractility program.  Tirasemtiv selectively activates the fast skeletal muscle troponin complex by increasing its sensitivity to calcium and, in preclinical studies, demonstrated increases in skeletal muscle force in response to neuronal input and delays in the onset and reductions in the degree of muscle fatigue.  In previously conducted Phase IIa clinical trials in patients with ALS, tirasemtiv appeared generally well-tolerated, and demonstrated encouraging trends to improvement in patients’ functional abilities and increases in measures of respiratory and skeletal muscle strength and endurance.  BENEFIT-ALS is a Phase IIb, multi-national, double-blind, randomized, placebo-controlled, clinical trial designed to evaluate the safety, tolerability and potential efficacy of tirasemtiv in patients with ALS.

About Cytokinetics

Cytokinetics is a clinical-stage biopharmaceutical company focused on the discovery and development of novel small molecule therapeutics that modulate muscle function for the potential treatment of serious diseases and medical conditions. Cytokinetics’ lead drug candidate from its cardiac muscle contractility program, omecamtiv mecarbil, is in Phase II clinical development for the potential treatment of heart failure.

Amgen Inc. holds an exclusive license worldwide to develop and commercialize omecamtiv mecarbil and related compounds, subject to Cytokinetics’ specified development and commercialization participation rights. Cytokinetics is independently developing tirasemtiv, a fast skeletal muscle activator, as a potential treatment for diseases and medical conditions associated with neuromuscular dysfunction. Tirasemtiv is currently the subject of a Phase II clinical trials program and has been granted orphan drug designation and fast track status by the U.S. Food and Drug Administration and orphan medicinal product designation by the European Medicines Agency for the potential treatment of amyotrophic lateral sclerosis, a debilitating disease of neuromuscular impairment.

Cytokinetics is collaborating with Astellas Pharma Inc. to develop CK-2127107, a skeletal muscle activator structurally distinct from tirasemtiv, for non-neuromuscular indications. All of these drug candidates have arisen from Cytokinetics’ muscle biology focused research activities and are directed towards the cytoskeleton. The cytoskeleton is a complex biological infrastructure that plays a fundamental role within every human cell. Additional information about Cytokinetics can be obtained at www.cytokinetics.com.

Source: Cytokinetics, Inc. via Globenewswire

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The Robert A. Stehlin Campaign for ALS (R.A.S.C.A.L.S.) is an all-volunteer 501(c)(3) charity. 100% of all funds raised go to building awareness, treatment research and development, plus ALS family assistance. There are no administrative costs.

Contributions are tax-deductible.

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