Amorfix Announces Progress on ALS Program

TORONTO, Canada, March 20, 2013 /CNW/ — Amorfix Life Sciences announced today that it has furthered the development of the first effective blood test to diagnose amyotrophic lateral sclerosis (ALS) by cloning ultra-high affinity antibodies that detect a misfolded version of the enzyme superoxide dismutase 1 (SOD1), which has been implicated  in the development of the disease.

“The generation of these high quality antibodies significantly advances the development of a highly sensitive and simple blood test to diagnose ALS by measuring misfolded SOD1 in the plasma of patients” said Amorfix CSO, Co-founder and Chairman of the Board Dr. Neil Cashman.  “We have made great progress in a relatively short period of time and continue to push towards getting this much needed diagnostic test in the clinic and on the market as quickly as possible.”

These ultra-high affinity antibodies will also be instrumental in the development of a treatment for ALS in both our therapeutic and vaccine initiatives.  The Amorfix therapeutic antibody program, through the collaboration with Biogen-Idec, continues to advance through preclinical animal models.  In addition, the Company has a strategic partnership with Pan-Provincial Vaccine Enterprise Inc. (PREVENT) to develop ALS therapeutic vaccines against misfolded SOD1

“We continue to see excellent progress and exciting results from all of our ALS programs,” said Dr. Robert Gundel, Amorfix President and CEO.  “Our business strategy is to harness major scientific discoveries with our internal scientific expertise and proprietary technology and form strategic partnerships and alliances with other companies to turn these discoveries into products as quickly as possible.”  The ALS program is a great representation of the Company’s approach to disease management with a product to diagnose the disease early-on and strategic partnerships to develop therapeutic antibodies and vaccines for treatment.”

ALS is a disease that is difficult to diagnose and treat.  At the present time, clinicians must rely on a combination of clinical findings and indirect testing to confirm a diagnosis of ALS, as there is no diagnostic test or biomarker at their disposal. The average survival time after diagnosis is 3 to 5 years which indicates that there are no effective treatments available for patients once diagnosed with ALS.  The Company believes that the availability of a reliable blood test would represent an important advancement in the management of this devastating disease, allowing clinicians to diagnose the disease earlier and provide better treatment. The projected market for such a diagnostic test is approximately $250M.  In addition, the Company’s therapeutic and vaccine programs represent potential blockbuster products that could improve patient survival by treating existing disease or slowing or preventing the onset of disease.

About ALS
ALS is a common neuromuscular disease, affecting an estimated 120,000 people of all races and ethnic backgrounds worldwide. According to the ALS Association, more than 5,600 people in the U.S. are diagnosed with ALS annually and an estimated 30,000 Americans have ALS at any given time.

About Amorfix
Amorfix Life Sciences Ltd. (TSX:AMF) is an early-stage product development company developing therapeutic antibodies and diagnostics targeting misfolded protein diseases.  Amorfix utilizes its computational discovery platform, ProMIS™, to predict novel Disease Specific Epitopes (DSEs) on the molecular surface of misfolded proteins.  Using this technology, Amorfix is developing novel antibody therapeutics and companion diagnostics for cancer and amyotrophic lateral sclerosis (ALS). In addition, Amorfix has developed two proprietary technologies to specifically identify very low levels of misfolded proteins in a biological sample: Epitope Protection™ and AMFIA™, an ultra-sensitive dual-bead immunoassay.  Use of these technologies has generated a cerebrospinal fluid (CSF) screening test for both Alzheimer’s disease (AD) and mild cognitive impairment (MCI), and an ultrasensitive method for detecting the hallmark of AD, aggregated beta-Amyloid, in brain tissue, CSF and blood from animal models of AD. For more information about Amorfix, visit www.amorfix.com.

The TSX has not reviewed and does not accept responsibility for the adequacy or accuracy of this release. This information release may contain certain forward-looking information. Such information involves known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements to be materially different from those implied by statements herein, and therefore these statements should not be read as guarantees of future performance or results. All forward-looking statements are based on the Company’s current beliefs as well as assumptions made by and information currently available to it as well as other factors.  Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. Due to risks and uncertainties, including the risks and uncertainties identified by the Company in its public securities filings, actual events may differ materially from current expectations. The Company disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, unless required by law.

ProMIS™, Epitope Protection™ and AMFIA™ are trademarks of Amorfix Life Sciences Ltd.

SOURCE: Amorfix Life Sciences Ltd.

For further information:

Dr. Robert Gundel
President and Chief Executive Officer
Amorfix Life Sciences Ltd.
Tel: (416) 847-6957
Fax: (416) 847-6899
bob.gundel@amorfix.com
Warren Whitehead
Chief Financial Officer
Amorfix Life Sciences Ltd.
Tel: (416) 644-7358
Fax: (416) 847-6899
warren.whitehead@amorfix.com

Results of NurOwn™ Clinical Trial Suggest Efficacy in ALS Patients

Data Indicate Initial Clinical Benefit in Overall Clinical and Respiratory Function

NEW YORK, NY and PETACH TIKVAH, ISRAEL, March 21, 2013 — BrainStorm Cell Therapeutics, a leading developer of adult stem cell technologies for neurodegenerative diseases, today reported some of the final results from a clinical study evaluating the company’s NurOwn™ technology in 12 ALS patients. NurOwn is a proprietary, first-of-its-kind technology for the propagation and differentiation of autologous Mesenchymal Stem Cells (MSCs) into NeuroTrophic Factor (NTF)-secreting cells. The data were presented yesterday, Wednesday, March 20, 2013 during the 65th Annual Meeting of the American Academy of Neurology (AAN) in San Diego, California.

An oral and poster presentation were made in the Emerging Science Session by Principal Investigator Dimitrios Karussis, M.D., Ph.D., entitled, “Analysis of 12 Patients with Amyotrophic Lateral Sclerosis (ALS) Treated with Autologous Differentiated Mesenchymal Stem Cells: a Phase I/II Clinical Trial.” Karussis reported a significantly slower decline in overall clinical and respiratory function, as measured by the ALS Functional Rating Score (ALSFRS-R) and Forced Vital Capacity (FVC) score respectively, in the six patients that received an intrathecal (IT) injection of the cells in the six months following treatment, as compared to the three months preceding treatment. The study concluded that in addition to establishing the safety of the treatment protocol, initial indications of clinical benefit were observed, which require further confirmation in additional trials. The company is currently conducting a Phase IIa dose-escalating trial pursuant to recent acceleration by the Israeli Ministry of Health.

“These encouraging results confirm the importance and therapeutic potential of NurOwn as a breakthrough treatment for patients with ALS,” said Prof. Karussis, Head of the Neuroimmunology Laboratory, Department of Neurology, Hadassah Medical Center, Jerusalem. “Additionally, beyond its benefit in treating patients with ALS, NurOwn may have utility in the treatment of other severe neurodegenerative and neuroimmunological conditions including multiple sclerosis and Parkinson’s disease.”

“We are excited by these data and the potential of NurOwn to positively impact the lives of patients with ALS,” said Alon Natanson, Chief Executive Officer of BrainStorm. “We look forward to continuing to advance this potentially important therapy. To that end, we have begun a Phase IIa dose-escalating trial at Hadassah and plan to launch a multi-center Phase II trial in the USA later this year in order to further validate the results that were presented today.”

About NurOwn™
NurOwn is an autologous, adult stem cell therapy technology that differentiates bone marrow-derived mesenchymal stem cells (MSC) into specialized, neuron-supporting cells. These neuron-supporting cells (known as “MSC-NTF” cells) secrete neurotrophic, or nerve-growth, factors for PROTECTION of existing motor neurons, PROMOTION of motor neuron growth, and RE-ESTABLISHMENT of nerve-muscle interaction. The ability to differentiate mesenchymal stem cells into MSC-NTF cells, and confirmation of their activity and potency before transplantation, makes NurOwn a first-of-its-kind approach for treating neurodegenerative diseases. More information about NurOwn™ can be found at http://brainstorm-cell.com/index.php/science-a-technology/-nurown.

About ALS
One of the most common neuromuscular diseases worldwide, Amyotrophic lateral sclerosis (ALS), sometimes called Lou Gehrig’s disease, is a rapidly progressive, invariably fatal neurological disease that attacks the nerve cells responsible for controlling voluntary muscles. As many as 30,000 people in the United States have ALS and an estimated 5,000 Americans are newly diagnosed each year. The disease belongs to a group of disorders known as motor neuron diseases, which are characterized by the gradual degeneration and death of motor neurons. There is currently no cure available for ALS.

About BrainStorm Cell Therapeutics, Inc.
BrainStorm Cell Therapeutics Inc. is a biotechnology company engaged in the development of first-of-its-kind adult stem cell therapies derived from autologous bone marrow cells for the treatment of neurodegenerative diseases. The Company holds the rights to develop and commercialize its NurOwn technology through an exclusive, worldwide licensing agreement with Ramot, the technology transfer company of Tel Aviv University. For more information, visit the company’s website at www.brainstorm-cell.com.

Safe Harbor Statement – Statements in this announcement other than historical data and information constitute “forward-looking statements” and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.’s actual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as “may”, “should”, “would”, “could”, “will”, “expect”, “likely”, “believe”, “plan”, “estimate”, “predict”, “potential”, and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, risks associated with BrainStorm’s limited operating history, history of losses; minimal working capital, dependence on its license to Ramot’s technology; ability to adequately protect the technology; dependence on key executives and on its scientific consultants; ability to obtain required regulatory approvals; and other factors detailed in BrainStorm’s annual report on Form 10-K and quarterly reports on Form 10-Q available at http://www.sec.gov. These factors should be considered carefully, and readers should not place undue reliance on BrainStorm’s forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management’s beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements.

SOURCE: BrainStorm Cell Therapeutics, 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.

New Breathing Device Helps Patients Battle Lou Gehrig’s Disease

From the Brigham and Women’s Hospital Health Blog

ALS-Treatment
Dr. Christopher Ducko (right) implanted a diaphragm pacing system to help extend the life of ALS patient Scott Murphy (left).

Scott Murphy, a Massachusetts father of three, was diagnosed with amyotrophic lateral sclerosis (ALS) in 2004. ALS, also known as Lou Gehrig’s disease, is a neurological disease that leads to a gradual loss of muscle function. As ALS progresses, patients lose their ability to perform the most basic tasks, like walking, swallowing and even breathing. Most patients with ALS only live 3-5 years after diagnosis. Miraculously, Scott has been able to survive well beyond that; however, continued weakening of his chest muscles and diaphragm (the muscle that helps draw air into the lungs) recently posed a new threat to his health.

Until recently, the only way to help patients like Scott was the use of a mechanical ventilator, which can be confining and costly. But a Brigham and Women’s Hospital (BWH) surgical team, led by Dr. Christopher Ducko in the Division of Thoracic Surgery, has given Scott and other ALS patients a better option in delaying their need for a ventilator. In October 2012, BWH became the first hospital in New England to implant a diaphragm pacing system in an ALS patient.

During the surgery, small electrodes, which condition the weak diaphragm muscle and improve its function, were implanted in Scott’s diaphragm. Research indicates that this will help Scott breathe more easily and postpone his need for a ventilator by up to 18 months. Additionally, unlike a ventilator, the diaphragm pacing system operates quietly and makes it possible for Scott to be mobile.

“This innovative diaphragm pacing system is an exciting development in the treatment of ALS. It has the potential to improve and extend the lives of hundreds of ALS patients. It is thrilling that our BWH team is able to bring this new treatment to ALS patients in New England,” said Dr. Ducko.

Though the diaphragm pacing system can’t completely restore Scott’s ability to do many of things he once enjoyed, it does have the potential to ease the burden of his illness. “The surgery will improve the quality of my life,” said Scott. “It will allow me to live longer, get around easier, do the things I love, and enjoy more time with my family.”

BWH researchers are also conducting research on ALS to understand its causes and progression to assist in the development of new therapies for ALS.  Read more about our ALS research:

# # #

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.

With A.L.S. in Family, Chief at Bloomberg Joins Fight

Daniel L. Doctoroff, second from right, chief executive of Bloomberg L.P., at Columbia University’s Motor Neuron Center.
Daniel L. Doctoroff, second from right, chief executive of Bloomberg L.P., at Columbia University’s Motor Neuron Center.

By , posted at the New York Times. February 6, 2013 •

Daniel L. Doctoroff watched in pain as his father developed a limp one day, was found to have Lou Gehrig’s disease, and died within two years. Then an uncle also developed symptoms of the same disease, and died soon after.

Now Mr. Doctoroff, like many other relatives of Lou Gehrig’s disease victims, worries that he or his children may someday develop the illness.

But unlike many, he is in a position to try to do something about it. At a time when scientists are making rapid gains in the genetic roots of many diseases, Mr. Doctoroff, a former deputy mayor and private equity investor, is working with Mayor Michael R. Bloomberg and a private equity director, David M. Rubenstein, to put together a $25 million package of donations to support research to try to cure this rare and usually fatal degenerative neurological illness.

“This is a devastating disease,” Mr. Doctoroff said in an interview this week in the glass high-rise on the Upper East Side that houses Bloomberg L.P., the mayor’s media and financial information company, where Mr. Doctoroff is now chief executive. “Up to now, there’s been basically no hope. I have the resources, and I think it’s my obligation to do that.”

The gift is part of a wave of investment based on the booming field of genomic analysis. The money will go to a project called Target A.L.S., a consortium of at least 18 laboratories, including ones at Columbia and at Johns Hopkins, the mayor’s alma mater, working to find biological “targets,” like gene mutations, and the biochemical changes they cause in the spinal cord, that could be used to test potential drug therapies for the disease, formally known as amyotrophic lateral sclerosis.

It comes on top of a previous $15 million gift by Mr. Doctoroff, Bloomberg Philanthropies and other donors. By comparison, the National Institutes of Health, the single largest source of research financing for the disease, expects to give $44 million in 2013.

This is not Mr. Bloomberg’s first time supporting charitable causes that are dear to his close associates. The mayor quietly gave at least $1 million to put the name of his top deputy mayor, Patricia E. Harris, on a new academic center at her alma mater, Franklin & Marshall College in Lancaster, Pa.

Mr. Doctoroff said the conversation about A.L.S. in which he got Mr. Bloomberg involved “lasted about five seconds.” He declined to say what share of the money each of the three donors was giving.

Mr. Rubenstein, a founder of the Carlyle Group, said Wednesday that he had long been fascinated with A.L.S. because of its association with Gehrig, the baseball player who died of it. He wondered why more than 70 years later so little progress had been made in treating it.

He said he jumped at the chance to join in because he thought that A.L.S. research was underfinanced owing to the rarity of the disease, and that even a small amount of money could make a big difference.

In the Bloomberg administration, where he was deputy mayor for economic development and rebuilding from 2002 to 2008, Mr. Doctoroff was best known for his dogged — and ultimately dashed — attempt to bring the 2012 Olympics to New York City. (London got the Games.) Now that he has left City Hall, he no longer rides his bike to work — he says the 2.6-mile route from the Upper West Side to his office is too short — but he sometimes runs.

At Bloomberg, he sits in front of a conference room with walls of hot-pink glass, while carp swim in a giant fish tank nearby. He keeps no family photos or other personal mementos on his desk, and talking about his family’s disease history does not seem easy for him.

A.L.S. is rare, with about 2 new cases diagnosed a year per 100,000 people, according to the A.L.S. Association. A vast majority of cases are “sporadic,” in people who have no family history, while only 5 to 10 percent of cases are inherited. There appear to be no racial, ethnic or socioeconomic predispositions.

There is some speculation about environmental factors, like exposure to toxic chemicals and high physical activity that athletes might endure, “but nothing firm,” said Christopher E. Henderson, a researcher at Columbia and the Target A.L.S. project’s scientific director. Some researchers suspect a link between A.L.S. and head trauma suffered by professional football players.

Mr. Doctoroff’s father, Martin, an appeals court judge in Michigan, received the diagnosis in 2000 and died in 2002. One of Martin Doctoroff’s brothers, Michael, was found to have the disease in 2009 and died in 2010.

“When my father contracted the disease and passed away, it was very easy to chalk it up to bad luck,” Mr. Doctoroff said. “When my uncle got it, it obviously had broader implications.”

Given his family history, Mr. Doctoroff estimates that there is a 50-50 chance that he has the gene, C9orf72, that could lead to A.L.S. But he has chosen not to be tested, which would have implications not just for him but for his three children. “It’s very personal, but I’m not sure that I want to know,” he said.

Even when family members develop the disease, it can occur at vastly different ages, so he could still be in suspense even after testing. “Assuming you have the gene, you don’t know when you would actually get the disease,” he said. His uncle was 71. His father was 66. He is now 54.

Sheelagh McNeill contributed reporting.

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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.

 

Up-and-Coming ALS Mice Leave Scientists ConFUSed

Mouse engineers presented the latest models overexpressing the amyotrophic lateral sclerosis gene fused in sarcoma (FUS) at “New Frontiers in Neurodegenerative Disease Research,” a Keystone Symposium held 4-7 February 2013 in Santa Fe, New Mexico. These animals have been four years in the making. This is a long time even for mice (see ARF related news story). Part of the challenge was that the protein appears to regulate its own expression, so it was difficult to ramp it up to abnormally high levels, said Shuo-Chien Ling of the University of California, San Diego. Ling presented his model on a poster. Eric Huang of the University of California, San Francisco, introduced his new mice. These strains only partly recapitulate the pathology seen in human disease or other ALS models, dying young with moderate neurodegeneration. Scientists at the meeting puzzled over how they relate to human disease.

Overall, FUS transgenic mice developed by multiple research groups exhibit signs of age-dependent, progressive motor neuron disease akin to ALS, such as difficulty moving, faulty coordination, muscle wasting, paralysis, and early death. Ling also found that pathology was dose dependent. Mild disease ensued from one FUS transgene, while severe symptoms developed in mice with two copies. Both teams observed that mutant FUS caused worse symptoms than wild-type, although the normal protein was sufficient to cause disease when expressed at high levels. This matches well with previous rat and fruit fly models, commented Udai Pandey of the Louisiana State University Health Sciences Center in New Orleans, who was not involved in the presented research. Together, the new and the old models suggest that FUS gains a toxic function when mutated, he said (Verbeeck et al., 2012; Huang et al. 2012; Xia et al., 2012).

tdpmouse_lg

Huang’s mice express wild-type human FUS or an arginine-521-cysteine (R521C) mutation linked to human disease. By one to three months of age, their motor coordination began to suffer, their muscles were wasting away, and their neuromuscular junctions were losing their innervation. Most of the animals died a few weeks after symptoms started. However, Huang and colleagues were surprised to see the mice retained more neurons than typically seen in ALS models. At the end stage of disease they still possessed half the motor neurons normally found in the anterior horn, whereas in ALS models expressing mutant human superoxide dismutase 1 (SOD1), 90 percent of those neurons are gone at the end of life, Huang said.

To investigate this discrepancy, Huang collaborated with Steven Finkbeiner of the Gladstone Institutes in San Francisco. The researchers cultured neurons from the mice and confirmed that FUS expression was less toxic than other proteins implicated in neurodegeneration, such as TDP-43 or huntingtin. They did see stunted dendrites in transgenic neurons expressing either mutant or wild-type FUS. Going back to the mice, the researchers stained tissue and saw stubby dendrites in the sensorimotor cortex and cervical spinal cord. This synaptic defect might explain the mice’s symptoms even if their neurons survive, suggested the researchers.

How do Ling’s mice compare? They express wild-type FUS or the ALS-linked mutations arginine-514-guanine or R521C. These mice also retained more motor neurons than do other models. Although their motor control declined with age, they lived for a year or more. Limited FUS overexpression may make their disease mild, Ling said. Ling found that the human transgene dampened production of endogenous mouse FUS, keeping levels relatively low overall. Homozygotes with two copies of the human gene expressed about one and a half times the normal amount of FUS. Disease progressed faster in those animals. They had widespread neurodegeneration, losing about a third of their motor neurons and dying at 40 days of age.

The results jibe with a recently published mouse model expressing wild-type human FUS (Mitchell et al., 2012). Those authors also observed that FUS transgenes turned down endogenous FUS production, and that two transgene copies were necessary to produce disease. And here, too, 40 percent of motor neurons remained in the lumbar spinal cord even though homozygous mice died by 12 weeks of age.

What, then, do these mice tell researchers about the mechanism of FUS-based disease? In coimmunoprecipitation experiments, Huang observed FUS complexes. “The mutant protein has a higher propensity to form aggregates with itself and also with the endogenous wild-type protein,” he said. He proposed it could sequester normal FUS from its interactions with mRNA. Huang and Ling both observed mRNA splicing defects in their animals, and Ling’s homozygous FUS mutants showed splicing patterns similar to FUS knockdowns. Ling also saw accumulation of p62, which indicates blocked autophagy pathways.

Ling suggested that FUS normally ensures RNA is properly processed. Altering FUS homeostasis would result in both a loss of this normal splicing function and a gain of toxic function, because excess FUS inhibits autophagy. This latter angle opens up a potential treatment strategy, Pandey noted, because the drug rapamycin induces autophagy. An immunosuppressant used to prevent transplant rejection, rapamycin is also under study as a potential cancer drug.

Ling said no new mouse models for ALS fully mimic the human condition. Neither he nor Huang saw the widespread neurodegeneration and cytoplasmic FUS aggregates typical of the proteinopathy in people. Researchers modeling TDP-43 proteinopathy have made similar observations (see ARF related news story), and, of course, researchers in Alzheimer’s and Parkinson’s have for many years had to make do with partial models. ALS researchers have been “spoiled” by the SOD1 mouse, Ling suggested, with its rapid and severe disease resulting from one point mutation. Unfortunately, SOD1 mutations represent a tiny sliver of all ALS cases. For FUS and TDP-43 mice to better mimic human symptoms, they might require a second hit. “We need to make much more thorough models,” he said. —Amber Dance.

Source: Alzheimer Research Forum

# # #

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.

Spastic Paraplegia Foundation and Northeast ALS Consortium Announce Two Year, $200,000 Research Grant

SPF/NEALS Fellowship Grant intended to further cutting-edge research into ALS’s little-known cousin, Primary Lateral Sclerosis (PLS).

COLUMBUS, Ohio, February 21, 2013  — (24-7PressRelease) The Spastic Paraplegia Foundation (SPF) and the Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS) have announced the first Virginia Freer-Sweeney Clinical Research Training Fellowship in primary lateral sclerosis (PLS). The fellowship highlights another successful collaboration between the NEALS Upper Motor Neuron Taskforce and the SPF. This training fellowship offers two years of salary support of $90,000 per year plus $10,000 per year for educational activities. A complete request for application (RFA) can be found at http://www.alsconsortium.org/images/files/NEALS-SPF_Fellowship_Final.pdf.

The objective of this fellowship is to train outstanding junior clinical researchers to rapidly and efficiently translate advances in neuroscience into treatments for people with PLS. While little known, PLS is a rare disease with close ties to amyotrophic lateral sclerosis (ALS) and another very rare disease called hereditary spastic paraplegia (HSP). Both PLS and HSP are debilitating upper-motor neuron diseases that result in difficulty with walking due to slowly progressive spasticity in the lower limbs. PLS also affects speech, swallowing and the fine motor movements of the hands. HSP is typically isolated to the lower extremities.

It is estimated that HSP and PLS affect some 30,000 individuals in North American and some 200,000 individuals worldwide.

ALS, PLS, and HSP are very closely related from a clinical point of view because they share common outward symptoms or phenotypes. Often doctors have to wait for symptoms to progress significantly before finalizing a diagnosis of ALS, for example. They also share a common mechanism of pathology that makes them very interesting to researchers since discoveries in one yield benefits and insights into the others.

There are currently no treatments for PLS or HSP outside of some mild symptom relief. But, because these diseases open a window into the inner workings of some of the most interesting and mysterious cells in nature, upper motor neurons, they are attracting researchers from around the world who want to understand not only UMNs but how all cells function.

These discoveries stand to aid clinicians in the treatment all diseases, not just those associated with the central nervous system (CNS). It is for this reason, the SPF is proud to be partnering with NEALS in this important endeavor.

About the SPF

Founded in 2002, the Spastic Paraplegia Foundation, Inc. is the only organization in the Americas dedicated to finding cures for hereditary spastic paraplegia (HSP) and primary lateral sclerosis (PLS). SPF is committed to providing information about for these disorders, creating opportunities for mutual support and sharing, and discovering the cures for HSP and PLS. Since its inception, SPF has raised more than $3M toward research into these ultra-rare conditions. For more information, please visit: www.sp-foundation.org

About NEALS

NEALS’s mission is to translate scientific advances into new treatments for people with amyotrophic lateral sclerosis (ALS) and motor neuron disease (MND) as rapidly as possible. NEALS offers expertise in clinical trial design and conduct. It functions as an academic clinical research organization, and a resource tool for ALS community. NEALS was founded in 1995. Its research and training activities are managed from two coordinating centers located at Massachusetts General Hospital and SUNY Upstate Medical University. NEALS members include over 100 clinical centers throughout the United States and Canada For more information, please visit: www.alsconsortium.org Media Contacts: SPF Allen Bernard Board member and media liaison 614-475-4562 – office 614-937-2316 – mobile abernie182@gmail.com NEALS Tara Lincoln NEALS Program Manager tlincoln@partners.org 617-724-7398

# # #

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.

Unique ALS ‘Exome-Sequencing’ Project Is Focus of New Grant

By Amy Madsen, originally posted at MDA/ALS  Newsmagazine

Obtaining genetic data from samples taken from 1,000 people with ALS is the goal of a $400,000 MDA grant to a MDA-NIH collaboration

Article Highlights:

  • MDA has awarded a $400,000 infrastructure grant to National Institutes of Health (NIH) researchers to perform exome sequencing on samples taken from 1,000 people with amyotrophic lateral sclerosis (ALS).
  • Data generated by the project will be made publicly available online, giving researchers around the world access to a large dataset to use in their research.
  • This data is expected to accelerate the pace of ALS research by helping scientists identify genes associated with the disease.
  • In a short video, MDA Vice President of Research Jane Larkindale discusses how exome sequencing significantly expands the existing resources available for scientists to use in their ongoing efforts to better understand ALS.

dna_blue_helix_tech

MDA has awarded a $400,000 grant to National Institutes of Health (NIH) Laboratory of Neurogenetics researchers to perform exome sequencing on samples taken from 1,000 people with sporadic amyotrophic lateral sclerosis (ALS). The project will be led by neurologist Bryan Traynor, head of the Neuromuscular Diseases Research Group at the NIH in Bethesda, Md.

Data generated by the first-of-its-kind project will be made publicly available online and is expected to accelerate the pace of ALS research by helping scientists identify genes associated with the disease.

The infrastructure award was made through MDA’s translational research program. In addition to MDA funding, the project will leverage resources through the Intramural Research Program at the NIH and adds value to tissue samples already available to researchers through the Coriell ALS Repository.

Exome sequencing decodes exons

Compared to previous generations of technology, exome sequencing is a faster and less expensive way to reveal the chemical “letters” that make up the human genome (DNA), and search for genes associated with human diseases.

As opposed to whole genome sequencing, in which a readout of an individual’s entire genome is produced, exome sequencing decodes only the stretches of DNA called exons, which contain instructions used in protein synthesis. (Introns, the DNA regions that do not contain information used to make proteins, are ignored.)

Although exons make up only about 1.5 percent of the genome, the vast majority of disease-causing mutations occur in these sections.

MDA-NIH project has a 12-month timeline

The exome-sequencing project, which is expected to be completed within 12 months, will produce genetic information for:

  • 360 deceased individuals who had the sporadic form of ALS, for whom post-mortem tissue samples are available; and
  • 640 samples stored at the Coriell ALS Repository from people (both living and deceased) with sporadic ALS.

(Only about 5 percent of ALS is familial, where there is a history of ALS in more than one family member; the other 95 percent occurs sporadically without any family history of the disease.)

Exome sequencing data from a large number of people unaffected by ALS will be used for comparison in analysis.

Identification of genes will speed ALS research

Researchers will be able to correlate much of the genetic information generated by the project with specific tissue samples that are accessible through Coriell, allowing for the seamless transitioning to many lines of further research.

Although samples will be taken from people with sporadic ALS, some will be found to have mutations in genes associated with familial ALS.

It is hoped the sequencing project also will uncover new genes that, when mutated, can cause ALS, as well as combinations of genes or genetic sequences that either increase the risk of getting the disease or modify its course.

Scientists will be able to use such data to better understand what processes are disrupted in ALS. The findings could lead to better diagnostic tests, and in turn to earlier or more precise diagnosis, and may point the way to various targets around which therapies can be developed.

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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.

Bloomberg Targets Lou Gehrig’s Disease

NEW YORK, New York, February 8, 2013 (UPI) — A donation of $25 million aims to streamline approaches to treat amyotrophic lateral sclerosis, or Lou Gehrig‘s disease, the U.S. donors say.

Daniel L. Doctoroff, chief executive officer and president of Bloomberg LP; David M. Rubenstein, co-CEO of The Carlyle Group; and Bloomberg Philanthropies said Target ALS is a $25 million three-year initiative to tackle ALS in a different way.

“While ALS scientists have made great progress in the last few years, their research too often occurs in silos, impeding discovery,” Doctoroff said in a statement. “Target ALS will provide an organizational framework for the world’s leading ALS researchers to share and coordinate their findings so that we can make progress toward therapies and a cure.”

Target ALS is the second phase of an accelerated research initiative of Project A.L.S., a New York-based foundation focused on finding and funding a cure for ALS.

“Collaboration is essential to build on the real progress that’s being made in the field of ALS research,” said Michael R. Bloomberg, philanthropist and mayor of New York City. “I’m proud to join Dan and David to launch this innovative new project and bring together the scientific, academic, healthcare and business communities to stop this horrible disease once and for all.”

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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 Study Shows Stem Cells’ Promise as Future ALS Treatment

A new study in the current issue of STEM CELLS Translational Medicine demonstrates how human stem cells can successfully engraft, survive and differentiate into mature neurons in the spinal cord of a rat with amyotrophic lateral sclerosis (ALS). The results offer new hope for those suffering from this disease, which generally ends in death within three to five years after diagnoses.

ALS (commonly known as Lou Gehrig’s disease) is characterized by the degeneration and death of the body’s motor neurons, leading to muscle atrophy, paralysis and death due to failure of the respiratory muscles. Despite studies that have improved our understanding of how ALS develops, there are no effective treatments. However, stem cell based-therapies have emerged as a potential solution.

“The transplantation of stem-cell derived neural progenitors may have beneficial effect not only for the replacement of motor neurons already lost, but also in counteracting degeneration and death of motor neurons,” said Roland Pochet, Ph.D., of the Université libre de Bruxelles, Belgium. He headed up the research team that included scientists from INSERM et Université Paris-Sud, and the Pasteur Institute, also in Paris, and Hannover Medical School in Germany.

The transplantation of stem-cell derived neural progenitors may have beneficial effect not only for the replacement of motor neurons already lost, but also in counteracting degeneration and death of motor neurons.

Spinal motor neurons have been successfully generated from various sources such as embryonic stem cells (ESCs) and neural stem cells (NSCs). Studies also have evaluated the therapeutic potential of bone marrow-derived human mesenchymal stem cells (MSCs) and human umbilical cord blood cells (UCBCs), but modest or no therapeutic benefit was obtained when transplanted in ALS patients.

In theory, induced pluripotent stem cells (iPSCs) derived from patients with neurodegenerative diseases, such as ALS, could be used to reverse the diseases. However, no report had yet described the fate of transplanted iPSCs into an ALS environment.

In the current study, the team wanted to learn how human-induced pluripotent stem cell- (iPSc) derived neural progenitors might affect ALS. The idea was inspired by a previous study in which they injected ALS rats with NSCs derived from other rats. “Although these cells undergo a massive apoptosis, after a few days of injection several survived, crossed the blood-brain barrier, differentiated and engrafted into the animals’ spinal cords,” Dr. Pochet explained.

Sixty days after transplantation, the iPSc-derived cells had efficiently engrafted in the rat’s spinal cord and were surviving, the team reported. Different neural progenitor, tissue and neuronal markers indicated that, over time, the transplanted cells differentiated into cells displaying a neuronal phenotype, the team learned.

“Our results,” Dr. Pochet said, “demonstrate proof-of-principle of survival and differentiation of human iPSc-derived neural progenitors in in vivo ALS environment, offering perspectives for the use of iPSc-based therapy in ALS.”

“This report of the ability of iPSCs to survive and differentiate in an ALS environment is certainly encouraging,” said Anthony Atala, MD, Editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. “The results suggest the potential of cell therapy for the field of neurobiology and disease treatment.”

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The full article, “Neural progenitors derived from human induced pluripotent stem cells survive and differentiate upon transplantation into a rat model of Amyotrophic Lateral Sclerosis,” can be accessed at http://www.stemcellstm.com

About STEM CELLS Translational Medicine: STEM CELLS TRANSLATIONAL MEDICINE (SCTM), published by AlphaMed Press, is a monthly peer-reviewed publication dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.

About AlphaMed Press: Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes two other internationally renowned peer-reviewed journals: STEM CELLS® (http://www.StemCells.com), celebrating its 31st year, is the world’s first journal devoted to this fast paced field of research. The Oncologist® (http://www.TheOncologist.com), also a monthly peer-reviewed publication, entering its 18th year, is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. All three journals are premier periodicals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines.

From: Durham, NC (PRWEB) February 14, 2013

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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.

Identification of Abnormal Protein May Help Diagnose, Treat ALS and Frontotemporal Dementia

Originally posted at Science Daily, February 12, 2013 •

Amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, and frontotemporal dementia (FTD) are devastating neurodegenerative diseases with no effective treatment. Researchers are beginning to recognize ALS and FTD as part of a spectrum disorder with overlapping symptoms.

Now investigators reporting online February 12 in the Cell Press journal Neuron have discovered an abnormal protein that first forms as a result of genetic abnormalities and later builds up in the brains of many patients with either disease.

“In identifying the novel protein that abnormally accumulates in the brains of affected patients, we have uncovered a potentially new therapeutic target and biomarker that would allow clinicians to confirm diagnosis of the diseases,” says senior author Dr. Leonard Petrucelli, Chair of Neuroscience at Mayo Clinic in Florida.

By analyzing brain tissue from patients with ALS or FTD, Dr. Petrucelli and his team discovered that the abnormal protein, which they call C9RANT, is generated as a result of repeat expansions of nucleotides in the noncoding region of the C9ORF72 gene. These expansions are the most common cause of ALS and FTD. “Simply put, an error in the highly regulated cellular process through which proteins are generated causes the abnormal production of C9RANT,” explains Dr. Petrucelli.

The researchers discovered the protein C9RANT after creating a novel antibody to specifically detect it. The ability to detect C9RANT in individuals’ cerebrospinal fluid may provide a valuable diagnostic and prognostic tool for identifying patients carrying the C9ORF72 repeat expansion and for then tracking the progression of the disease in these at-risk individuals.

“Although it remains to be shown whether C9RANT is causing the cell death or toxicity associated with disease symptoms, our discovery offers a potential target to prevent neuronal loss in patients carrying the C9ORF72 repeat expansion,” says Dr. Petrucelli.

The concept that abnormal proteins accumulate and can be toxic to cells is not new. In fact, tau protein forms tangles in Alzheimer’s disease and alpha-synuclein forms clumps in Parkinson’s disease. Just as new therapies are being developed to break down the protein aggregates associated with these diseases, developing a therapeutic strategy to target C9RANT aggregates may also prove beneficial.

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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.