‘RNA Sponge’ Mechanism May Cause ALS/FTD Neurodegeneration

Posted by Site Administrator on April 11, 2013

The most common genetic cause of both ALS (amyotrophic lateral sclerosis) and FTD (frontotemporal dementia) was recently identified as an alteration in the gene C9orf72. But how the mutation causes neurodegenerative disease appeared mysterious.

Researchers at Emory University School of Medicine have demonstrated that this ALS/FTD mutation may be harmful because it creates an “RNA sponge,” soaking up an important regulatory protein that binds RNA.

The results were published online Monday in the Proceedings of the National Academy of Sciences, Early Edition.

“We think that the RNA itself is part of the disease mechanism,” says co-author Thomas Wingo, MD, assistant professor of neurology at Emory University School of Medicine. “In both cell culture and fruit flies, we’ve been able to show that we can add back the protein depleted by the RNA and ameliorate the problem.”

The finding provides insight into the mechanism of disease in ALS and FTD, both in cases where C9orf72 is altered and in other cases. It suggests some forms of ALS/FTD may have common elements with other neurodegenerative disorders caused by noncoding repeats, such as myotonic dystrophy, spinocerebellar ataxia and fragile X-associated tremor/ataxia syndrome.

The senior author is Peng Jin, PhD, professor of human genetics at Emory University School of Medicine. The first authors are a former graduate student, Zihui Xu, PhD, now at Huazhong University of Science and Technology in China, and research specialist Mickael Poidevin.

ALS is a fatal disease in which motor neurons in the brain and spinal cord degenerate. As the illness progresses, patients lose the ability to walk, talk and breathe. FTD is a form of dementia in which the patients primarily experience deterioration in behavior, personality or language.

Many neurologists and researchers consider these conditions as sharing clinical and pathological features. Mutations in several genes have been linked to both ALS and FTD, which suggests that they have a common mechanism. However, most cases are considered sporadic, meaning that they don’t have a clear family history.

In 2011, a mutation was identified within C9orf72 as the most common genetic cause of ALS and FTD, accounting for 5 to 7 percent of cases of each disease. The mutation doesn’t seem to affect the protein encoded by C9orf72. Instead, it expands a block of repetitive DNA, so that the sequence “GGGGCC” is repeated hundreds of times outside the parts of the gene that encode protein.

This looks similar to “noncoding repeat” expansions responsible for other neurodegenerative disorders such as myotonic dystrophy, spinocerebellar ataxia and fragile X-associated tremor/ataxia syndrome.

Some researchers have reported that the GGGGCC repeat produces RNA that is translated into an unusual protein that aggregates in cells. These protein aggregates are thought to be toxic to neurons. Emory researchers have an alternative explanation: the GGGGCC repeat RNA itself is toxic.

The Emory team tested the effects of producing the GGGGCC repeat RNA, which proved toxic to cultured mammalian neuronal cells and caused neurodegeneration in fruit flies. When the repeat RNA was produced in flies’ motor neurons, the flies had reduced motor activity.

The repeat RNA appears to be harmful because, when overproduced, it sequesters a protein called Pur alpha, which sticks to the GGGGCC repeats. Scientists had previously found that Pur alpha is necessary for neuronal development and is involved in the transport of RNA within neurons. Making neuronal cells or flies produce more Pur alpha to compensate reverses the toxicity caused by the RNA, the Emory scientists found.

“For ALS and FTD, this suggests a disease-fighting strategy of targeting either the toxic RNA itself or its interaction with Pur alpha,” Jin says. “It also hints that there is a common RNA-based mechanism contributing to several neurodegenerative diseases.”

Sequestering Pur alpha appears to cause its redistribution within the neurons of patients affected by ALS/FTD. The Emory team was able to detect clumpy “inclusions” containing Pur alpha in samples of brain tissue from individuals with C9orf72 mutations – and also in other individuals with FTD but without C9orf72 mutations.

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The research was supported by the National Institute for Neurological Disorders and Stroke (R01 NS051630 and R21NS067461) and the Atlanta Veterans Administration Medical Center.

Reference:

Z. Xu, M. Poidevin, X. Li, Y. Li, L. Shu, D.L. Nelson, H. Li, M. Gearing, T.S. Wingo and P. Jin. Expanded GGGGCC repeat RNA associated with amyotrophic lateral sclerosis and frontotemporal dementia causes

SOURCE: Emory Health Sciences

Contact: Quinn Eastman
404-727-7829
qeastma@emory.edu

 

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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.

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Johns Hopkins Researchers Discover New Clues About How ALS Develops

Posted by Site Administrator on April 10, 2013
Role of cells other than motor neurons much larger than anticipated

BALTIMORE, Maryland, March 31, 2013 — Johns Hopkins scientists say they have evidence from animal studies that a type of central nervous system cell other than motor neurons plays a fundamental role in the development of amyotrophic lateral sclerosis (ALS), a fatal degenerative disease. The discovery holds promise, they say, for identifying new targets for interrupting the disease’s progress.

In a study described online in Nature Neuroscience, the researchers found that, in mice bred with a gene mutation that causes human ALS, dramatic changes occurred in oligodendrocytes—cells that create insulation for the nerves of the central nervous system—long before the first physical symptoms of the disease appeared. Oligodendrocytes located near motor neurons—cells that govern movement—died off at very high rates, and new ones regenerated in their place were inferior and unhealthy.

The researchers also found, to their surprise, that suppressing an ALS-causing gene in oligodendrocytes of mice bred with the disease—while still allowing the gene to remain in the motor neurons—profoundly delayed the onset of ALS. It also prolonged survival of these mice by more than three months, a long time in the life span of a mouse. These observations suggest that oligodendrocytes play a very significant role in the early stage of the disease.

johns_hopkins_medicine

“The abnormalities in oligodendrocytes appear to be having a negative impact on the survival of motor neurons,” says Dwight E. Bergles, Ph.D., a co-author and a professor of neuroscience at the Johns Hopkins University School of Medicine. “The motor neurons seem to be dependent on healthy oligodendrocytes for survival, something we didn’t appreciate before.”

“These findings teach us that cells we never thought had a role in ALS not only are involved but also clearly contribute to the onset of the disease,” says co-author Jeffrey D. Rothstein, M.D., Ph.D., a professor of neurology at Johns Hopkins and director of the Johns Hopkins Medicine Brain Science Institute.

Scientists have long believed that oligodendrocytes functioned only as structural elements of the central nervous system. They wrap around nerves, making up the myelin sheath that provides the “insulation” that allows nerve signals to be transmitted rapidly and efficiently. However, Rothstein and others recently discovered that oligodendrocytes also deliver essential nutrients to neurons, and that most neurons need this support to survive.

The Johns Hopkins team of Bergles and Rothstein published a paper in 2010 that described in mice with ALS an unexpected massive proliferation of oligodendrocyte progenitor cells in the spinal cord’s motor neurons, and that these progenitors were being mobilized to make new oligodendrocytes. The researchers believed that these cells were multiplying because of an injury to oligodendrocytes, but they weren’t sure what was happening. Using a genetic method of tracking the fate of oligodendrocytes, in the new study, the researchers found that cells present in young mice with ALS were dying off at an increasing rate in concert with advancing disease. Moreover, the development of the newly formed oligodendrocytes was stalled and they were not able to provide motor neurons with a needed source of cell nutrients.

To determine whether the changes to the oligodendrocytes were just a side effect of the death of motor neurons, the scientists used a poison to kill motor neurons in the ALS mice and found no response from the progenitors, suggesting, says Rothstein, that it is the mutant ALS gene that is damaging oligodendrocytes directly.

Meanwhile, in separate experiments, the researchers found similar changes in samples of tissues from the brains of 35 people who died of ALS. Rothstein says it may be possible to see those changes early on in the disease and use MRI technology to follow progression.

“If our research is confirmed, perhaps we can start looking at ALS patients in a different way, looking for damage to oligodendrocytes as a marker for disease progression,” Rothstein says. “This could not only lead to new treatment targets but also help us to monitor whether the treatments we offer are actually working.”

ALS, also known as Lou Gehrig’s disease, named for the Yankee baseball great who died from it, affects nerve cells in the brain and spinal cord that control voluntary muscle movement. The nerve cells waste away or die, and can no longer send messages to muscles, eventually leading to muscle weakening, twitching and an inability to move the arms, legs and body. Onset is typically around age 50 and death often occurs within three to five years of diagnosis. Some 10 percent of cases are hereditary.

There is no cure for ALS and there is only one FDA-approved drug treatment, which has just a small effect in slowing disease progression and increasing survival.

Even though myelin loss has not previously been thought to occur in the gray matter, a region in the brain where neurons process information, the researchers in the new study found in ALS patients a significant loss of myelin in one of every three samples of human tissue taken from the brain’s gray matter, suggesting that the oligodendrocytes were abnormal. It isn’t clear if the oligodendrocytes that form this myelin in the gray matter play a different role than in white matter—the region in the brain where signals are relayed.

The findings further suggest that clues to the treatment of other diseases long believed to be focused in the brain’s gray matter—such as Alzheimer’s disease, Huntington’s disease and Parkinson’s disease—may be informed by studies of diseases of the white matter, such as multiple sclerosis (MS). Bergles says ALS and MS researchers never really thought their diseases had much in common before.

Oligodendrocytes have been under intense scrutiny in MS, Bergles says. In MS, the disease over time can transform from a remitting-relapsing form—in which myelin is attacked but then is regenerated when existing progenitors create new oligodendrocytes to re-form myelin—to a more chronic stage in which oligodendrocytes are no longer regenerated. MS researchers are working to identify new ways to induce the creation of new oligodendrocytes and improve their survival. “It’s possible that we may be able to dovetail with some of the same therapeutics to slow the progression of ALS,” Bergles says.

Other Johns Hopkins researchers involved in the study include Shin H. Kang, Ph.D.; Ying Li, Ph.D.; Ileana Lorenzini, M.S.; and Lyle Ostrow, M.D., Ph.D.

This research was supported by grants from the National Institutes of Health’s National Institute of Neurological Disorders and Stroke (NS 051509), the ALS Association, P2ALS, the Robert Packard Center for ALS Research at Johns Hopkins and the Brain Science Institute.

SOURCE: John Hopkins Medicine

Media Contact:

Stephanie Desmon
410-955-8665
sdesmon1@jhmi.edu

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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.

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Cytokinetics Inc. Announces Initiation of First-Time-in-Humans, Phase I Clinical Trial of CK-2127107

Posted by Site Administrator on April 10, 2013

SAN FRANSCISCO, California, April 1, 2013 – Cytokinetics, Incorporated announced today the initiation of a first-time-in-humans, Phase I clinical trial of CK-2127107 in healthy male volunteers. Cytokinetics is developing CK-2127107, a novel small molecule activator of the fast skeletal muscle troponin complex, for the potential improvement of skeletal muscle function in diseases and medical conditions associated with neuromuscular dysfunction, muscular weakness, and/or muscle fatigue. Like tirasemtiv, the lead drug candidate from the company’s skeletal muscle activator program, CK-2127107 slows the rate of calcium release from the regulatory troponin complex of fast skeletal muscle fibers, which sensitizes the sarcomere to calcium.

CK-2127107 was discovered in connection with Cytokinetics’ optimization of a different chemical series than that which produced tirasemtiv, which is currently being evaluated in BENEFIT-ALS (Blinded Evaluation of Neuromuscular Effects and Functional Improvement with Tirasemtiv in ALS). BENEFIT-ALS is an international, double-blind, randomized, placebo-controlled, Phase IIb clinical trial designed to evaluate the safety, tolerability and potential efficacy of tirasemtiv in patients with amyotrophic lateral sclerosis (ALS). Advancing CK-2127107 to Phase I evaluation in healthy subjects is consistent with Cytokinetics’ corporate strategy to characterize a potential back-up compound to tirasemtiv in humans and to enable the evaluation of fast skeletal muscle troponin activation in a potentially broader set of clinical indications.

The Phase I clinical trial of CK-2127107 is a double-blind, randomized, placebo-controlled study designed to assess the safety, tolerability, and pharmacokinetics of single ascending oral doses of CK-2127107 administered to healthy adult males in a three period, escalating dose, crossover design. The primary objective of this study is to determine the safety and tolerability of single doses of CK-2127107 administered orally to healthy male volunteers. The secondary objective is to evaluate the pharmacokinetic profile of single doses of CK-2127107.

“This first-time-in-humans clinical trial of CK-2127107 builds on our expertise in the biology of skeletal muscle function,” stated Fady Malik, MD, PhD, Cytokinetics’ Senior Vice President, Research and Early Development. “Advancing CK-2127107 provides us an opportunity to develop a pipeline of drug candidates focused on skeletal muscle weakness resulting from an array of diseases associated with muscle wasting or primary neuromuscular dysfunction.”

“The initiation of this Phase I clinical trial is further demonstration of Cytokinetics’ commitment to build a portfolio of drug candidates with novel mechanisms that leverage our expertise in the biology of the cytoskeleton and our pioneering pharmacology associated with muscle contractility,” stated Robert I. Blum, Cytokinetics’ President and CEO. “CK-2127107 is the sixth novel chemical entity that has arisen from our research and development activities to proceed to human clinical testing.”

Background on Fast Skeletal Muscle Activators

Skeletal muscle contractility is driven by the sarcomere, the fundamental unit of skeletal muscle contraction. It is a highly ordered cytoskeletal structure composed of several key proteins. The first, skeletal muscle myosin, is the cytoskeletal motor protein that converts chemical energy into mechanical force through its interaction with a second protein, actin. A set of regulatory proteins, which includes tropomyosin and several types of troponin, make the actin-myosin interaction dependent on changes in intracellular calcium levels. Cytokinetics’ skeletal muscle contractility program is focused to the discovery and development of small molecule skeletal sarcomere activators and leverages Cytokinetics’ expertise gained from its ongoing discovery and development of cardiac sarcomere activators, including the cardiac myosin activator omecamtiv mecarbil, now in Phase IIb clinical development as a potential treatment for heart failure. In non-clinical models, skeletal sarcomere activators have demonstrated pharmacological activity that may lead to new therapeutic options for diseases associated with aging, muscle wasting, and neuromuscular dysfunction. The clinical effects of muscle wasting, fatigue and loss of mobility can range from decreased quality of life to, in some instances, life-threatening complications. By directly improving skeletal muscle function, a small molecule activator of the skeletal sarcomere may potentially enhance physical performance and quality of life in patients with conditions marked by muscle weakness, including neuromuscular diseases such as ALS, myasthenia gravis, cachexia, sarcopenia and general frailty associated with aging.

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 (excluding Japan) to develop and commercialize omecamtiv mecarbil and related compounds, subject to Cytokinetics’ specified development and commercialization participation rights. Cytokinetics is independently developing tirasemtiv and CK-2127107, both fast skeletal muscle activators, as potential treatments for diseases and medical conditions associated with aging, muscle wasting or 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 in which treatment with tirasemtiv produced potentially clinically relevant pharmacodynamic effects in Phase II trials. 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.

This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”). Cytokinetics disclaims any intent or obligation to update these forward-looking statements, and claims the protection of the Act’s Safe Harbor for forward-looking statements. Examples of such statements include, but are not limited to, statements relating to Cytokinetics’ research and development activities, including the conduct, design and results of clinical trials, the significance and utility of clinical trial results, and the properties and potential benefits of Cytokinetics’ skeletal muscle activators, including tirasemtiv and CK-2127107, and other drug candidates. Such statements are based on management’s current expectations, but actual results may differ materially due to various risks and uncertainties, including, but not limited to, Cytokinetics anticipates that it will be required to conduct at least one confirmatory Phase III clinical trial of tirasemtiv in ALS patients which will require significant additional funding, and it may be unable to obtain such additional funding on acceptable terms, if at all; potential difficulties or delays in the development, testing, regulatory approvals for trial commencement, progression or product sale or manufacturing, or production of Cytokinetics’ drug candidates that could slow or prevent clinical development or product approval, including risks that current and past results of clinical trials or preclinical studies may not be indicative of future clinical trials results, patient enrollment for or conduct of clinical trials may be difficult or delayed, Cytokinetics’ drug candidates may have adverse side effects or inadequate therapeutic efficacy, the U.S. Food and Drug Administration or foreign regulatory agencies may delay or limit Cytokinetics’ or its partners’ ability to conduct clinical trials, and Cytokinetics may be unable to obtain or maintain patent or trade secret protection for its intellectual property; Amgen’s decisions with respect to the design, initiation, conduct, timing and continuation of development activities for omecamtiv mecarbil; Cytokinetics may incur unanticipated research and development and other costs or be unable to obtain additional financing necessary to conduct development of its products; Cytokinetics may be unable to enter into future collaboration agreements for its drug candidates and programs on acceptable terms, if at all; standards of care may change, rendering Cytokinetics’ drug candidates obsolete; competitive products or alternative therapies may be developed by others for the treatment of indications Cytokinetics’ drug candidates and potential drug candidates may target; and risks and uncertainties relating to the timing and receipt of payments from its partners, including milestones and royalties on future potential product sales under Cytokinetics’ collaboration agreements with such partners. For further information regarding these and other risks related to Cytokinetics’ business, investors should consult Cytokinetics’ filings with the Securities and Exchange Commission.

Contact:

Joanna L. Goldstein

Manager, Corporate Communications & Marketing

(650) 624-3000

Source: Cytokinetics, Inc. via Thomson Reuters ONE

HUG#1689285

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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.

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Amorfix Announces Progress on ALS Program

Posted by Site Administrator on March 28, 2013

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

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Results of NurOwn™ Clinical Trial Suggest Efficacy in ALS Patients

Posted by Site Administrator on March 26, 2013
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.

—

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New Breathing Device Helps Patients Battle Lou Gehrig’s Disease

Posted by Site Administrator on March 25, 2013

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:

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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.

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

Posted by Site Administrator on March 25, 2013
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.

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Up-and-Coming ALS Mice Leave Scientists ConFUSed

Posted by Site Administrator on March 20, 2013

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

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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.

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

Posted by Site Administrator on March 20, 2013
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

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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.

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

Posted by Site Administrator on March 20, 2013

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.

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