Categories: Spotlight

Genervon Clinical Trial Update

clock January 15, 2015

It was announced, via press release, that a compound being pursued by Genervon Biopharmaceuticals LLC may have been effective in improving the ability of one person with ALS to speak and swallow.  It is paramount to note that this report is from a single patient, who was exposed to the drug GM6 though a compassionate use patient trial.   Further, this data alone is unlikely to be sufficient evidence for FDA approval of GM604 (aka GM6) as an effective therapy for ALS. Further analysis of GM6 is highly likely to occur both in and out of clinical trial settings.

The PALS participating in the compassionate use trial is male and was diagnosed with ALS nearly 10 years ago. According to Genervon, he has been a quadriplegic and on a ventilator since 2008. The purpose of this study was to gather data from later stage ALS patients and compare it to data from a phase 2 trial done in early stage ALS patients. The company conducted a number of tests on patients’ cerebrospinal fluid (CSF) to attempt to determine if their compound had any measurable effect on proposed biomarkers of ALS thought to be found in CSF, including SOD1, Cystatin C, and tau.

Earlier clinical trials of Genervon include a Phase 1 in healthy volunteers and a Phase 2 trial on 12 people with ALS.  The double blind placebo controlled trial was conducted over a period of 12 weeks with PALS receiving the drug (or placebo) intravenously during the first two weeks only, with follow up visits after that. CSF samples were collected before being given drug (baseline), at completion of treatment program (week 2), and at the end of the observational period (week 12). This trial’s main objective was to measure changes in biomarkers found within CSF overtime and to determine if GM6 was safe and tolerated well by PALS.  Results from this study have not yet been published by Genervon, however it put out a press release in October 2014 claiming that they saw a “statistically significant” effect on both clinical and biomarker data in both ALS and PD clinical trials. 

It is the opinion of ALSTDI that this trial was too small and too short to statistically measure an effect on disease progression.  However, we believe that Genervon should continue its effort with their compound, including the organization and execution of additional clinical trials.

What is GM6?

Described as an “endogenous signaling master regulator,” GM6 seems to be a unique compound created to regulate a specific aspect of cell health, specifically motor neurons. There are many things which motor neurons require to be healthy and part of a vibrant system, including a well-regulated abundance of different proteins called neurotrophins or neurotrophin factors. These include brain-derived neurotrophic factor (BDNF), glial derived neurotrophic factor (GDNF), and mononeurotrophic factor (MNTF) among others.  GM6 is proposed as a regulator of MNTF.  MNTF is believed to play a role in nearly every aspect of motor neuron development; including initial differentiation, maintenance, survival, axonal growth, and inervation of axons into muscles. Genervon believes that GM6 regulates, directly or in part, the expression of more than 4000 genes in the body, including some which are involved in ALS biology.

Helpful Links:

About GM6: http://www.als.net/ALS-Research/116/ALS-Topics/

ALS.net Statement on Phase 2a Clinical Trial: http://www.als.net/Media/5470/News/

Genervon Press Releases: http://www.genervon.com/genervon/about_pressreleases.php 

Washington Post "ALS patients press FDA for quick access to controversial biotech drug"

ALS Forum Thread: http://www.als.net/forum/yaf_postsm396374_Genervon-Announces-Phase-2a-Trial-Results.aspx

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Categories: Spotlight

ALS, on cloud C9

clock April 18, 2014

C9ORF72 RNA foci repeat expansion motor neuron ALS MND FTD FTLD timeline

 

The Whole C9 Yards Explore our 2014 timeline to learn more about emerging strategies to diagnose and treat C9 ALS. 

Since the discovery of C9orf72 in 2012, the most common form of sporadic and familial ALS identified to date, potential underlying mechanisms are unraveling at a rapid pace. And, potential strategies to diagnose and treat this form of the disease are beginning to emerge.

In just the last two years alone, genetic test for C9orf72 ALS (C9 ALS) entered the clinic.

PET imaging technique, developed by Katholieke Universiteit Leuven’s Koen Van Laere MD PhD and Università di Torino’s Adriano Chiò MDemerged – opening the door to predicting the outcome of people with C9 ALS. An MRI method, developed by Trinity College Dublin’s Peter Bede MD, which aims to help anticipate cognitive challenges, surfaced. And, a new map charting the spread of C9 ALS created by the research teams of Universitätsklinikum Ulm’s Heiko Braak MD and University of Pennsylvania’s John Trojanowski MD PhD may help clinicians in the future predict the course of their patients' disease. 

In addition, the first genetic modifier of C9 ALS, TMEM 106B, was discovered – paving the way toward a genetic test for C9 ALS-FTD.

“This is one of the first modifiers that could really explain why some people get ALS and FTD,” says Mayo Clinic’s Rosa Rademakers PhD.

All about RNA?

A potential antisense therapy, which aims to reduce levels of possibly toxic repeat-rich C9 RNAs, is in the preclinical stage. And, an initiative to discover RNA-targeted small molecules led by Scripps Institute’s Matthew Disney PhD launched.

C9ORF72 Rademakers RNA foci repeat expansion motor neuron ALS MND FTD FTLD

 

Don't repeat that Nearly 40% of inherited cases of ALS appear to be caused, at least in part, by expanded repeat sequences in the C9orf72 gene. Image: Courtesy of Nature Publishing Group.

Key questions remain.  Expanded C9 RNAs appear to make motor neurons more vulnerable to ALS according to studies led by Jeff Rothstein MD PhDBut whether the reduction of these RNAs alone is sufficient to treat people with C9 ALS remains an open question.

Toxic proteins also may contribute to the destruction of motor neurons  according to studies led by Ludwig Maximilians Universität München’s Christian Haass PhD and Mayo Clinic’s Len Petrucelli PhDAnd, according to studies led by La Trobe University’s Julie Atkin PhD, the reduction of C9orf72 protein, may in part make the removal of misfolded proteins more difficult – further contributing to the disease.

What’s more, existing mouse models of the disease do not appear to exhibit key symptoms of ALS according to University of Massachusetts’ Bob Brown MD PhD– making the development of potential therapies challenging.

"It is important to keep striving for models that actually recaptiulate the pathology, because then you start to learn which pieces of the C9 puzzle actually lead to the disease," says ALS Therapy Development Institute's Fernando Vieira MD.  

Testing the limits

The utility of genetic tests also remains limited. 

People at high risk of developing C9 ALS can be detected by existing methods. But identifying people who will develop the disease remains tricky to do. 

The reason, at least in part, is that C9 ALS appears to be one of a growing number of forms of ALS that may be oligogenic in nature. Multiple mutations in multiple genes may contribute to the onset and progression of the disease.

C9ORF72 Rademakers RNA foci repeat expansion motor neuron ALS MND FTD FTLD

 

Standardized tests? Existing blood tests help identify people with C9 ALS by detecting expanded repeat-rich RNAs. But according to a study led by University of Umeå's Peter Andersen MD, nearly 8% of people may diagnosed incorrectly due to a lack of testing standards. Image: Courtesy of Nature Publishing Group.

An alteration in at least one other gene linked to ALS can be detected in people with C9 ALS - at least in some cases according to results from Marka Blitterswijk MD PhD, now at Mayo Clinic in Florida.

“It is probably the tip of the iceberg,” says University of Massachusetts’ Bob Brown MD PhD. “It is clear that we can find more than one variant in a person with ALS.”

What’s more, existing genetic tests only help identify people with C9 ALS.  The size of the expanded RNA – at least in key cells isolated from the blood and the skin – do not appear to correlate with the progression rate of their disease.

“There is little we can do with repeat length to predict clinical outcome,” says Rosa Rademakers PhD.

***

To learn more about C9orf72 ALS, check out ALS Antisense and Sensibility. To find out more about emerging diagnostic strategies for the disease, check out C9 Comes Into Focus.

References

Akimoto, C. et al. (2014) A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories.  Journal of Medical Genetics doi:10.1136/jmedgenet-2014-102360Abstract  |  Full Text  

Haeusler, A.R. et al. (2014) C9orf72 nucleotide repeat structures initiate molecular cascades of disease.  Nature 507(7491), 195-200. Abstract  |  Full Text  (Subscription Required)

van Blitterswijk, M. et al. (2014) TMEM106B protects C9ORF72 expansion carriers against frontotemporal dementia.  Acta Neuropathologica 127(3), 397-406.  Abstract  |  Full Text (Subscription Required)

Gallagher, M.D. et al. (2014) TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions. Acta Neuropathologica 127(3), 407-418.  Abstract  |  Full Text (Subscription Required)

Cistaro, A. et al. (2014) The metabolic signature of C9ORF72-related ALS: FDG PET comparison with nonmutated patients. European Journal of Nuclear and Molecular Imaging doi: 10.1007/s00259-013-2667-5 Abstract  |  Full Text  (Subscription Required)

Van Laere, K., Vanhee, A., Verschueren, J., De Coster, L., Driesen, A., Dupont, P., Robberecht, W. and Van Damme, P.  (2014) Value of 18Fluorodeoxyglucose-Positron-Emission Tomography in Amyotrophic Lateral Sclerosis: A Prospective Study.  JAMA Neurology doi: 10.1001/jamaneurol.2014.62.  Abstract  |  Full Text (Subscription Required)

Farg, M.A. et al. (2014) C9ORF72, implicated in amytrophic lateral sclerosis and frontotemporal dementia, regulates endosomal trafficking. Human Molecular Genetics doi: 10.1093/hmg/ddu068 Abstract  |  Full Text

Waite, A.J., Bäumer, D., East, S., Neal, J., Morris, H.R., Ansorge, O., Blake and D.J. (2014) Reduced C9orf72 protein levels in frontal cortex of amyotrophic lateral sclerosis and frontotemporal degeneration brain with the C9ORF72 hexanucleotide repeat expansion. Neurobiology of Aging doi: 10.1016/j.neurobiolaging.2014.01.016. Abstract  |  Full Text (Subscription Required)

Lee, Y.B. et al. (2013) Hexanucleotide repeats in ALS/FTD form length-dependent RNA foci, sequester RNA binding proteins, and are neurotoxic.  Cell Reports 5(5), 1178-1186.Abstract | Full Text

Donnelly, C.J. et al. (2013) RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense intervention. Neuron 80(2), 415-428. Abstract  |  Full Text (Subscription Required)

Sareen, D. et al. (2013) Targeting RNA foci in iPSC-derived motor neurons from ALS patients with a C9ORF72 repeat expansion. Science Translational Medicine 5(208), 208ra149. Abstract  |  Full Text  (Subscription Required)

Lagier-Tourenne, C. et al. (2013) Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration. Proceedings of the National Academy of Sciences 110(47), E4530-E4539.  Abstract  |  Full Text  (Subscription Required)

Almeida, S. et al.  (2013) Modeling key pathological features of frontotemporal dementia with C9ORF72 repeat expansion in iPSC-derived human neurons. Acta Neuropathologica 126(3), 385-399. Abstract  |  Full Text

van Blitterswijk, M. et al. (2013) C9ORF72 repeat expansions in cases with previously identified pathogenic mutations.  Neurology 81(15), 1332-1341.  Abstract Full Text

van Blitterswijk, M. et al. (2013) Association between repeat sizes and clinical and pathological characteristics in carriers of C9ORF72 repeat expansions (Xpansize-72): a cross-sectional cohort study.  Lancet Neurology 12(10), 978-988.Abstract Full Text  (Subscription Required)

Panda, S.K., Wefers, B., Ortiz, O., Floss, T., Schmid, B., Haass, C., Wurst, W. and Kühn, R. (2013) Highly efficient targeted mutagenesis in mice using TALENs. Genetics 195(3), 703-713.  Abstract  | Full Text (Subscription Required)

Brettschneider, J. et al. (2013) Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Annals of Neurology 74(1), 20-38. Abstract  |  Full Text (Subscription Required)

Bede, P., Bokde, A.L., Byrne, S., Elamin, M., McLaughlin, R.L., Kenna, K., Fagan, A.J., Pender, N., Bradley, D.G. and Hardiman, O. (2013)  Multiparametric MRI study of ALS stratified for the C9orf72 genotype. Neurology 81(4), 361-369. Abstract  |  Full Text  (Subscription Required)

Xi, Z. et al. (2013) Hypermethylation of the CpG island near the G4C2 repeat in ALS with a C9orf72 expansion. American Journal of Human Genetics 92(6), 981-989.  Abstract  |  Full Text

Xu, Z. et al. (2013) Expanded GGGGCC repeat RNA associated with amyotrophic lateral sclerosis and frontotemporal dementia causes neurodegeneration.  Proceedings of the National Academy of Sciences 110(19), 7778-7783.  Abstract  |  Full Text

Mori, K. et al. (2013) hnRNP A3 binds to GGGGCC repeats and is a constituent of p62-positive/TDP43-negative inclusions in the hippocampus of patients with C9orf72 mutations.Acta Neuropathologica 125(3), 1178-1186. Abstract  |Full Text (Subscription Required)

Mori, K. et al. (2013) The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS. Science 339(6125), 1335-1338. Abstract  |  Full Text  (Subscription Required)

Ash, P.E. et al. (2013) Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALS. Neuron 77(4) 639-646. Abstract  |  Full Text (Subscription Required)

Williams, K.L., Fifita, J.A., Vucic, S., Durnall, J.C., Kiernan, M.C., Blair, I.P. and Nicholson, G.A. (2013) Pathophysiological insights into ALS with C9ORF72 expansions. Journal of Neurology, Neurosurgery and Psychiatry 84(8), 931-935. Abstract  |  Full Text (Subscription Required)

Gómez-Tortosa, E. et al. (2013) C9ORF72 hexanucleotide expansions of 20-22 repeats are associated with frontotemporal deterioration. Neurology 80(4), 366-370. Abstract  |  Full Text  (Subscription Required)

Reddy, K., Zamiri, B., Stanley, S.Y., Macgregor, R.B. Jr and Pearson, C.E. (2013) The disease-associated r(GGGGCC)n repeat from the C9orf72 gene forms tract length-dependent uni- and multimolecular RNA G-quadruplex structures. Journal of Biological Chemistry 288(14), 9860-9866. Abstract  |  Full Text

Fratta, P., Mizielinska, S., Nicoll, A.J., Zloh, M., Fisher, E.M., Parkinson, G. and Isaacs, A.M. (2012)  C9orf72 hexanucleotide repeat associated with amyotrophic lateral sclerosis and frontotemporal dementia forms RNA G-quadruplexes. Scientific Reports 2, 2016.  Abstract  |  Full Text

van Blitterswijk, M. et al. (2012) Evidence for an oligogenic basis of amyotrophic lateral sclerosis. Human Molecular Genetics 21(17), 3776-3784. Abstract  |  Full Text

Majounie, E., et al. (2012) Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Lancet Neurology 11(4), 323-330. Abstract  |  Full Text

DeJesus-Hernandez, M., et al. (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72(2), 245-256.  Abstract  |  Full Text

Renton, A. E., et al. (2011) A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72(2), 257-268. Abstract  |  Full Text

Vance, C. et al. (2006) Familial amyotrophic lateral sclerosis with frontotemporal dementia is linked to a locus on chromosome 9p13.2-21.3. Brain 129(4), 868-876. Abstract | Full Text

 

 

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Categories: Spotlight

Timeline: The Whole C9 Yards - 2014

clock April 18, 2014

About 1 out of 10 cases of ALS appear to be linked to repeat expansions in the C9orf72 gene, the most common form of the disease identified to date. 

Researchers are working hard to how these repeat sequences may contribute to ALS in hopes to create a treatment for people with C9 ALS.  And, develop tools to anticipate their needs.

A genetic test is now available - enabling clinicians to confirm the diagnosis. Cutting-edge imaging techniques are beginning to emerge - paving the way to predicting outcomes. And, the first potential treatment strategy, developed in partnership with ISIS pharmaceuticals, entered the pipeline.

Ahead of the 2014 meeting of the American Academy of Neurology (AAN), ALS Today takes a look back at key advances in C9 ALS in this interactive timeline. Click on the timeline to learn more about emerging strategies to diagnose, track and treat this form of the disease.

***

To learn more about C9orf72 ALS, check out ALS on cloud C9. To find out more about emerging treatment strategies for the disease, check out  ALS Antisense and Sensibility.

Image credits: Mark Lythgoe PhD & Chloe Hutton PhD, Wellcome Images; Jonathan Charles, Flickr; George Shuklin, Wikimedia Commons;  Judith Stoffer, National Institute of Genome Sciences; Stephen Neidle PhD, American Chemical Society; European Journal of Human Genetics, Nature Publishing Group; Nature Chemical Biology, Nature Publishing Group and Despicable Me 2 (Viva Press).

References

Akimoto, C. et al. (2014) A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories.  Journal of Medical Genetics doi:10.1136/jmedgenet-2014-102360Abstract  |  Full Text  

Haeusler, A.R. et al. (2014) C9orf72 nucleotide repeat structures initiate molecular cascades of disease.  Nature 507(7491), 195-200. Abstract  |  Full Text  (Subscription Required)

van Blitterswijk, M. et al. (2014) TMEM106B protects C9ORF72 expansion carriers against frontotemporal dementia.  Acta Neuropathologica 127(3), 397-406.  Abstract  |  Full Text (Subscription Required)

Gallagher, M.D. et al. (2014) TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions. Acta Neuropathologica 127(3), 407-418.  Abstract  |  Full Text (Subscription Required)

Cistaro, A. et al. (2014) The metabolic signature of C9ORF72-related ALS: FDG PET comparison with nonmutated patients. European Journal of Nuclear and Molecular Imaging doi: 10.1007/s00259-013-2667-5 Abstract  |  Full Text  (Subscription Required)

Van Laere, K., Vanhee, A., Verschueren, J., De Coster, L., Driesen, A., Dupont, P., Robberecht, W. and Van Damme, P.  (2014) Value of 18Fluorodeoxyglucose-Positron-Emission Tomography in Amyotrophic Lateral Sclerosis: A Prospective Study.  JAMA Neurology doi: 10.1001/jamaneurol.2014.62.  Abstract  |  Full Text (Subscription Required)

Farg, M.A. et al. (2014) C9ORF72, implicated in amytrophic lateral sclerosis and frontotemporal dementia, regulates endosomal trafficking. Human Molecular Genetics doi: 10.1093/hmg/ddu068 Abstract  |  Full Text

Waite, A.J., Bäumer, D., East, S., Neal, J., Morris, H.R., Ansorge, O., Blake and D.J. (2014) Reduced C9orf72 protein levels in frontal cortex of amyotrophic lateral sclerosis and frontotemporal degeneration brain with the C9ORF72 hexanucleotide repeat expansion. Neurobiology of Aging doi: 10.1016/j.neurobiolaging.2014.01.016. Abstract  |  Full Text (Subscription Required)

Lee, Y.B. et al. (2013) Hexanucleotide repeats in ALS/FTD form length-dependent RNA foci, sequester RNA binding proteins, and are neurotoxic.  Cell Reports 5(5), 1178-1186.Abstract | Full Text

Donnelly, C.J. et al. (2013) RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense intervention. Neuron 80(2), 415-428. Abstract  |  Full Text (Subscription Required)

Sareen, D. et al. (2013) Targeting RNA foci in iPSC-derived motor neurons from ALS patients with a C9ORF72 repeat expansion. Science Translational Medicine 5(208), 208ra149. Abstract  |  Full Text  (Subscription Required)

Lagier-Tourenne, C. et al. (2013) Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration. Proceedings of the National Academy of Sciences 110(47), E4530-E4539.  Abstract  |  Full Text  (Subscription Required)

Almeida, S. et al.  (2013) Modeling key pathological features of frontotemporal dementia with C9ORF72 repeat expansion in iPSC-derived human neurons. Acta Neuropathologica 126(3), 385-399. Abstract  |  Full Text

van Blitterswijk, M. et al. (2013) C9ORF72 repeat expansions in cases with previously identified pathogenic mutations.  Neurology 81(15), 1332-1341.  Abstract Full Text

van Blitterswijk, M. et al. (2013) Association between repeat sizes and clinical and pathological characteristics in carriers of C9ORF72 repeat expansions (Xpansize-72): a cross-sectional cohort study.  Lancet Neurology 12(10), 978-988.Abstract Full Text  (Subscription Required)

Panda, S.K., Wefers, B., Ortiz, O., Floss, T., Schmid, B., Haass, C., Wurst, W. and Kühn, R. (2013) Highly efficient targeted mutagenesis in mice using TALENs. Genetics 195(3), 703-713.  Abstract  | Full Text (Subscription Required)

Brettschneider, J. et al. (2013) Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Annals of Neurology 74(1), 20-38. Abstract  |  Full Text (Subscription Required)

Bede, P., Bokde, A.L., Byrne, S., Elamin, M., McLaughlin, R.L., Kenna, K., Fagan, A.J., Pender, N., Bradley, D.G. and Hardiman, O. (2013)  Multiparametric MRI study of ALS stratified for the C9orf72 genotype. Neurology 81(4), 361-369. Abstract  |  Full Text  (Subscription Required)

Xi, Z. et al. (2013) Hypermethylation of the CpG island near the G4C2 repeat in ALS with a C9orf72 expansion. American Journal of Human Genetics 92(6), 981-989.  Abstract  |  Full Text

Xu, Z. et al. (2013) Expanded GGGGCC repeat RNA associated with amyotrophic lateral sclerosis and frontotemporal dementia causes neurodegeneration.  Proceedings of the National Academy of Sciences 110(19), 7778-7783.  Abstract  |  Full Text

Mori, K. et al. (2013) hnRNP A3 binds to GGGGCC repeats and is a constituent of p62-positive/TDP43-negative inclusions in the hippocampus of patients with C9orf72 mutations.Acta Neuropathologica 125(3), 1178-1186. Abstract  |Full Text (Subscription Required)

Mori, K. et al. (2013) The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS. Science 339(6125), 1335-1338. Abstract  |  Full Text  (Subscription Required)

Ash, P.E. et al. (2013) Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALS. Neuron 77(4) 639-646. Abstract  |  Full Text (Subscription Required)

Williams, K.L., Fifita, J.A., Vucic, S., Durnall, J.C., Kiernan, M.C., Blair, I.P. and Nicholson, G.A. (2013) Pathophysiological insights into ALS with C9ORF72 expansions. Journal of Neurology, Neurosurgery and Psychiatry 84(8), 931-935. Abstract  |  Full Text (Subscription Required)

Gómez-Tortosa, E. et al. (2013) C9ORF72 hexanucleotide expansions of 20-22 repeats are associated with frontotemporal deterioration. Neurology 80(4), 366-370. Abstract  |  Full Text  (Subscription Required)

Reddy, K., Zamiri, B., Stanley, S.Y., Macgregor, R.B. Jr and Pearson, C.E. (2013) The disease-associated r(GGGGCC)n repeat from the C9orf72 gene forms tract length-dependent uni- and multimolecular RNA G-quadruplex structures. Journal of Biological Chemistry 288(14), 9860-9866. Abstract  |  Full Text

Fratta, P., Mizielinska, S., Nicoll, A.J., Zloh, M., Fisher, E.M., Parkinson, G. and Isaacs, A.M. (2012)  C9orf72 hexanucleotide repeat associated with amyotrophic lateral sclerosis and frontotemporal dementia forms RNA G-quadruplexes. Scientific Reports 2, 2016.  Abstract  |  Full Text

van Blitterswijk, M. et al. (2012) Evidence for an oligogenic basis of amyotrophic lateral sclerosis. Human Molecular Genetics 21(17), 3776-3784. Abstract  |  Full Text

Majounie, E., et al. (2012) Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Lancet Neurology 11(4), 323-330. Abstract  |  Full Text

DeJesus-Hernandez, M., et al. (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72(2), 245-256.  Abstract  |  Full Text

Renton, A. E., et al. (2011) A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72(2), 257-268. Abstract  |  Full Text

Vance, C. et al. (2006) Familial amyotrophic lateral sclerosis with frontotemporal dementia is linked to a locus on chromosome 9p13.2-21.3. Brain 129(4), 868-876. Abstract | Full Text

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Categories: Spotlight

Timeline: ALS 2013, A Year in Review

clock January 15, 2014

2013 has now come and gone. Lest the auld year be forgot, ALS Today turns back the clock - highlighting key advances in 2013 and key challenges going forward.

High-resolution ultrasound entered the ALS clinic, an emerging technique that aims to identify people with ALS with fewer EMGs. An ALS cognitive test, ECAS, was unveiled. A whole-brain imaging technique, MIDAS, emerged; opening the door to using MRS to monitor people with ALS. And, new insights into the spread of ALS may help physicians in the future to predict the course of their disease.

Potential therapies for ALS moved forward in the clinic. GlaxoSmithKline’s ozanezumab advanced to phase II across the globe. AB Science’s Masitinib neared phase III in Europe. And, potential stem cell treatments, Brainstorm’s NurOwn and Neuralstem’s NSI-266, reached phase II in Israel and the US.

New treatment strategies for ALS also emerged. In the US, Novartis’ Gilenya and the generic mexiletine moved into the ALS clinic. In China, the generic fasudil re-entered phase II. Misfolded SOD1-targeted antibodies including Neurimmune’s NI-204 entered the pipeline. And, GlaxoSmithKline’s potential ‘stress-buster’ GSK2606414 targeting PERK resurfaced.

Neurologists, however, remain divided on how to test these potential therapies in people with ALS. In the wake of the failure of Biogen-Idec/Knopp's dexpramipexole, a growing number of research teams launched phase IIA and larger phase IIB clinical trials to increase confidence in dose selection and phase II go/no go decisions. But others continue to evaluate these drugs in smaller phase II studies.

What's more, with the humanitarian device exemption looming large, neurologists remain at odds over recommending the NeuRX DPS and how best to evaluate its use.

Take a look back at 2013 by exploring our interactive timeline. Click on key advances to learn more.

Image Credits: Søren Storm Hansen, Flickr; Alice-Palace, Flickr; Judith Stoffer, National Institute of Genome and Medical Sciences; tnsasse, Flickr; Go, Dog,Go!, PD Eastman; Inside Star Wars Insider #133, Lucas Films LTD; Nature Publishing Group, UCDavis Biowiki and The Smithsonian Institution. 

Categories: Spotlight

Timeline: ALS 2012, A Year In Review

clock January 9, 2013

The year 2012 has now drawn to a close.  ALS Today turns back the clock - highlighting key advances in 2012 and key challenges going forward.

Monocytes, T-cells and oligodendrocytes emerged as potentially key players that could be targeted in ALS. Advances in induced pluripotent stem (iPS) cell technologies opened the door toward the discovery of new medicines for the disease.  Emerging antisense-based treatment strategies surfaced for C9- ALS, the most common form of ALS identified to date. GSK’s potential neuromuscular junction protector Ozanezumab (anti-NOGO A) approached phase II. And, Avanir’s emotionality-regulator Nuedexta, Novartis’ T cell sequesterer fingolimod (Gilenya), and the potential neuronal excitability-reducer mexiletine re-entered the pipeline – phase II clinical trials expected to begin sometime in 2013.

Key challenges, however, remain.  The first clinical reports of C9-ALS reawakened the debate about how to define inherited forms of the disease (fALS) and test for them. Clinical trials launched in 2012 hope to establish evidence-based clinical practice guidelines for the NeuRXNIV and feeding tube to help clinicians best meet their ALS patients’ respiratory and nutritional needs. And, the failure of ceftriaxone and dexpramipexole fueled the debate about which drugs to push forward in the clinic and how best to evaluate them.

Take a look back at 2012 by exploring our interactive timeline. Click on key advances and challenges ahead to learn more.

Images courtesy of Arcadian, Bradford Timeline, East Birmingham Hospital's Graham Beards MD, NIGMS' Judith Stoffer.

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Exercise: stretching the limits of ALS care

clock March 28, 2012

GDNF neurotrophin ALS

 

Bundle of nerves. Scientists at BrainStorm Cell Therapeutics hope to use patient-derived astrocyte-like cells to boost supplies of the neurotrophin GDNF in people with ALS. Image: Protein Data Bank

In people with ALS, the motor nerves deteriorate leading to muscle weakness and ultimately paralysis.  In hopes to stop this neurodegeneration in its tracks, researchers are looking towards substances called neutrophins including BDNF, GDNFIGF-1 and VEGF  to keep nerves healthy and plugged into muscles.  But delivering these protective substances safely at the right place, at the right time and at the right dose has turned out to be extremely difficult to do.  And, scientists remain unsure which one of these neurotrophins is the best choice for people with ALS to protect the motor nerves from further deterioration.

Studies suggest that moderate aerobic exercise such as stationary bicycling or treadmilling might have the potential to help keep muscles and nerves healthy longer in people with ALS by increasing levels of many of these protective substances in the brain and spinal cord. What’s more, a moderate workout might even help fight the disease by boosting energy supplies, removing damaged proteins and reducing inflammation.

Neurologists nevertheless remain reluctant to recommend specific exercise routines for their patients.  There simply is not enough clinical evidence according to experts to indicate which routines are safe and offer the most benefit to people with ALS.  New clinical trials promise to change that by putting exercise to the test in people with ALS.

Run, mouse, run

Exercise can keep your heart healthy and keep your spirits up. But according to experts, a short workout might do a lot more good for people with ALS. Certain forms of moderate aerobic exercise might help keep nerves plugged into muscles and protect them from destruction.

mouse exercise running wheel als

 

Mighty mouse.  Researchers often study the underlying benefits of moderate aerobic exercise in mice by providing a running wheel.  Image: Salk Institute of Biological Studies, San Diego.

Researchers first suspected that exercise might benefit people with ALS upon the discovery in the mid 1990s that a short aerobic workout boosted levels of neurotrophins - substances that protect motor neurons or trigger the growth of new motor neurons - in the brain. A team led by University of California Irvine neuroscientist Carl Cotman PhD reported in 1995 in rats that running for one week increased levels of BDNF in the brain more than two-fold.  And, researchers from the Cajal Institute in Madrid reported in 2000 and 2001 that increased levels of the neurotrophin IGF-1 following moderate aerobic exercise helped to protect the brain in rats from injury or neurodegenerative disease.

Scientists subsequently discovered that moderate aerobic exercise increased circulating levels of a number of neurotrophins in people including those with multiple sclerosis or a spinal cord injury.

Encouraged by the ability of short aerobic workouts to boost neuroprotective mechanisms, researchers in the early 2000s tested ALS mice to determine whether or not such routines could help slow down the disease.  In 2003 and 2005, scientists reported that running moderately increased the lifespan of ALS mice.  And, in 2009, scientists from the Université de Paris Descartes found that swimming significantly delayed clinical onset and dropped losses of motor neurons in the spinal cord of ALS mice by nearly 50%.

The power of exercise

BDNF brain exercise ALS

 

Growth spurt. Scientists discovered that moderate exercise induces the production of protective factors in the CNS. Here, the levels of BDNF are shown (yellow, red) in the brain of an exercised (b) vs. non-exercised (a) mouse. Adapted from Neeper, S.A. et al. (1995), Nature. Courtesy of Nature Publishing Group. All rights reserved.

Researchers however suspect that moderate aerobic exercise might have the potential to do much more to keep the motor nerves healthy in people with ALS. Exercise may help keep the power on in the motor nerves by boosting levels of oligodendrocytes: critical cells in the brain and spinal cord that are thought in part, to supply critical energy-making ingredients to mitochondria keeping the energy flowing in distal axons and nerve terminals.   Reporting in 2011, scientists from the University of California in Los Angeles found that mice that frequented the running wheel for one week boosted numbers of oligodendrocyte precursors called NG2+ cells more than two-fold in the spinal cord.  And, in 2009, scientists from the Université de Paris Descartes found that ALS mice which swam regularly maintained near healthy levels of spinal cord oligodendrocytes compared to unexercised mice which lost nearly a third of their oligodendrocytic populations.

What's more, exercise might keep neuroinflammation in check.  Researchers at the Université de Paris Descartes reported in 2009 that swimming regularly dropped levels of activated astrocytes in ALS mice to nearly those of healthy mice – reducing levels of potentially damaging inflammatory cytokines in the spinal cord.  And, scientists at the University of Illinois in Urbana reported in 2011 that providing access to a running wheel increased levels of microglia producing IGF-1 more than two-fold in healthy mice suggesting that moderate aerobic exercise might help push microglia from the neurotoxic to the neuroprotective mode.

“The potential effects of exercise are diverse,” says Johns Hopkins University School of Medicine Neurologist Nicholas Maragakis MD.  “That’s what makes exercise so appealing.”

And, these potential benefits might just be the tip of the iceberg.  A moderate aerobic workout according to a recent study in mice might even switch on intracellular vacuum cleaners within the motor nerves, reducing inflammation.  Called autophagosomes, these mini Hoovers could help keep levels of neuronal destruction down by swallowing up aggregated proteins and malfunctioning mitochondria that accumulate during the course of the disease - dropping levels of reactive oxygen species (ROS) that further deteriorate the motor nerves.  Looking ahead, the Baylor College of Medicine team hopes to evaluate whether or not this so-called exercise-induced autophagy could help protect against neurodegenerative disease.

"We do know that autophagy is likely a protective mechanism against these diseases," says Baylor College of Medicine internist Beth Levine MD who led the study. "Increasing autophagy may be a strategy to treat them."

Of mice to men

Translating these moderate aerobic workouts into specific routines for people with ALS however has been extremely challenging to do. And, the implementation of physical exercise into routine practice remains hotly debated and extremely controversial.

endurance exercise stationary bike

 

Spinning wheels. A growing number of researchers suspect that moderate aerobic exercise such as stationary bicycling might be helpful to people with ALS. But the use, the intensity and the duration of such routines remain controversial. Image: sirwiseowl, Flickr. 

Some neurologists worry that regular exercise could speed up the progression of the disease by turning up the production of reactive oxygen species (ROS), potentially damaging weakening muscles and increasing inflammation of the connecting nerves.

But a growing number of neurologists argue that physical inactivity could expose people with ALS to even greater health risks.  And, exercise in moderation could bring the benefits of exercise while minimizing the risk of worsening their condition.

“I do think that mobility is important,” says Johns Hopkins neurologist Nicholas Maragakis MD. “I usually tell them to exercise on an every other day basis.  [But] I don’t want them to be fatigued or have any muscle pain following an exercise regimen.” 

Most clinical studies on the books that evaluate the benefits and risks of exercise comes from studies that involve people with other neuromuscular diseases – particularly complications due to polio - not ALS.   

“There is no evidence that exercise is harmful to people with ALS,” says Oxford University neurologist Martin Turner MA PhD MRCP.  

Many neurologists therefore find themselves in a Catch-22.  Exercise could be helpful and could be good for the overall wellness of their patients.  But how much exercise is enough but not too much?  What kinds of workouts should they do?

With existing randomized controlled exercise studies extremely limited and conducted in fewer than 25 people with ALS, neurologists are unable to figure out which kinds of exercise are safe and offer the most benefits at the lowest risk for their patients.

“We need to know which type of exercise at what duration and intensity could be protective,” explains INSERM – Strasbourg neuroscientist Luc Dupuis PhD.

We can work it out

University of Lisbon physician Anabela Pinto MD PhD grew frustrated in the mid 1990s that she could not do more for her patients with ALS.  Noninvasive ventilation appeared to extend survival but did not improve their quality of life or slow down their disease.  In hopes to change that, she began to introduce exercise into their daily routine.

CPET exercise testing treadmill

 

Sweet oxygen. Experts perform cardio pulmonary exercise testing (CPET) to determine the maximum output of oxygen (VO2 max): a critical benchmark that indicates to researchers the point at which muscles could be overworked or damaged. Image: Salem Elizabeth, Flickr. 

Reporting in 1999, the University of Lisbon physicians found that a group of 8 people with ALS who exercised showed significant reductions in decline of breathing abilities after one year of rehabilitation (FVC, P < 0.002).  20 people with ALS participated in the controlled clinical trial.

The strategy her Santa Maria Hospital -based team developed is loosely based on a typical cardiac stress test.  Exercise either on a cycle ergometer or a treadmill ramped up to 60-65% oxygen output (about 70-75% heart rate) for about 10-20 minutes - sufficient intensity to keep weakening muscles moving but not overworking or damaging them.  Workouts are typically scheduled three times per week.

The idea: By performing aerobic exercise regularly for a short period of time, the team hopes to keep fast-twitch muscles critical to maintain optimal breathing rate and to power rapid motions moving; muscles which are especially vulnerable to atrophy in people with ALS.  

In subsequent years, the team implemented this supervised exercise program in their Lisbon-based clinic.  Non-invasive ventilation and body-weight support systems are provided if needed.

“Our current practice is to include exercise throughout the clinical evolution of the disease,” says Pinto.

Reporting the first results of her latest exercise study at the 2011 ALS/MND meeting in Australia last December, the University of Lisbon team found that people with ALS on this supervised exercise regimen showed significant signs of reduced functional decline (ALS-FRS) and increased survival post-rehabilitation (p = 0.04) over a one year period.  40 patients participated.

Now, the Santa Maria Hospital-based team is working hard to adapt these exercises for home use. And at the same time, the team is adjusting these routines to accommodate people with ALS that might have trouble adhering to such regular workouts due to deficits in executive function, estimated to affect as many as 50% of people with the disease.

“I am really interested in making this [exercise] program available to as many patients as possible,” says Pinto.

But the Neuromuscular Unit at Santa Maria Hospital is small.  The team’s aerobic exercise routines have only been tested in a few people with ALS.  Larger studies are needed according to experts to implement specific therapeutic workouts into routine practice.

neuromuscular junction als

 

NMJ Unplugged. In people with ALS, neuromuscular junctions can become unstable leading to the nerves being unplugged from muscles ultimately resulting in paralysis. Exercise may help stabilize these connections according to experts. John Wildgoose, Wellcome Images.

Now, a group of neurologists led by Johns Hopkins University School of Medicine neurologist Nicholas Maragakis MD are stepping up to the plate by launching a clinical trial to evaluate the benefits of exercise in people with ALS.  The clinical trial, which will take place over six months in four centers in the US, will put three forms of moderate exercise to the test in people with ALS: stationary bicycling (aerobic exercise), weightlifting (resistance exercise) and stretching (the standard of care).  Patients will be monitored for improvements in muscle strength/fatigue, signs of reduced functional decline and quality of life.  About 60 people with possible, probable or definite ALS are expected to participate. 

“The trial's power is to really study the safety and tolerability of exercise [in people with ALS],” explains Johns Hopkins School of Medicine neurologist Nicholas Maragakis MD.  “I think that will go a long way.”

Researchers however anticipate that workouts that experts ultimately develop for people with ALS will extend well outside the exercise gym.  By understanding the underlying mechanisms behind the benefits of these workouts, scientists hope to gain insight into the underlying mechanisms of this exercise-based neuroprotection to help them develop more effective medicines to fight the disease.

Scientists at Johns Hopkins School of Medicine hope to identify the underlying benefit of any workout found to be helpful in a future clinical trial by measuring levels of circulating neurotrophins and possibly looking for changes in muscle fiber composition in people with ALS following exercise.

The findings according to Luc Dupuis PhD, also at Germany's University of Ulm, could help scientists figure out how to fight one of the hardest aspects of the disease: denervation, when the motor nerves become unplugged from muscles leading to weakness and paralysis.

“During exercise, neuromuscular junctions are strengthened and stabilized,” explains Dupuis.  “Understanding what really happens during exercise might lead to a therapeutic strategy to treat ALS.” 

References - Clinical Studies

Lui, A.J. and Byl, N.N. (2009) A systematic review of the effect of moderate intensity exercise on function and disease progression in amyotrophic lateral sclerosis. Journal of Neurological Physical Therapy 33, 68-87. Abstract | Full Text  (Subscription Required)

Dalbello-Haas V, Florence JM, Krivickas LS. (2008) Therapeutic exercise for people with amyotrophic lateral sclerosis or motor neuron disease. Cochrane Database of Systematic Reviews 2, CD005229. Abstract | Full Text  (Subscription Required)

Rojas Vega, S., Abel, T., Lindschulten, R., Hollmann, W., Bloch, W. and Strüder, H.K. (2008) Impact of exercise on neuroplasticity-related proteins in spinal cord injured humans. Neuroscience 153(4), 1064-1070. Abstract | Full Text (Subscription Required)

Bello-Haas, V.D., Florence, J.M., Kloos, A.D., Scheirbecker, J., Lopate, G., Hayes, S.M., Pioro, E.P. and Mitsumoto, H. (2007) A randomized controlled trial of resistance exercise in individuals with ALS. Neurology 68, 2003-2007. Abstract | Full Text (Subscription Required)

Gold, S.M., Schulz, K.H., Hartmann, S., Mladek, M., Lang, U.E., Hellweg, R., Reer, R., Braumann, K.M. and Heesen C. (2003)  Basal serum levels and reactivity of nerve growth factor and brain-derived neurotrophic factor to standardized acute exercise in multiple sclerosis and controls. Journal of Neuroimmunology 138(1-2), 99-105. Abstract | Full Text (Subscription Required)

Drory VE, Goltsman E, Reznik JG, Mosek A, Korczyn AD. (2001) The value of muscle exercise in patients with amyotrophic lateral sclerosis.  Journal of Neurological Sciences 191, 133-137. Abstract | Full Text (Subscription Required)

Pinto, A.C., Alves, M., Nogueira, A., Evangelista, T., Carvalho, J., Coelho, A., de Carvalho, M. and Sales-Luís, M.L. (1999) Can amyotrophic lateral sclerosis patients with respiratory insufficiency exercise? Journal of Neurological Sciences 169, 69-75. Abstract | Full Text (Subscription Required)

References - Preclinical Studies

He, C. et al. (2012) Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis. Nature 481, 511-5. Abstract | Full Text (Subscription Required)

Kohman, R.A., Deyoung, E.K., Bhattacharya, T.K., Peterson, L.N. and Rhodes, J.S. (2011) Wheel running attenuates microglia proliferation and increases expression of a proneurogenic phenotype in the hippocampus of aged mice. Brain, Behavior and Immunity doi 10.1016/j.bbi.2011.10.006. Abstract | Full Text (Subscription Required)

Krityakiarana, W. et al. (2010) Voluntary exercise increases oligodendrogenesis in the spinal cord. International Journal of Neuroscience 120(4), 280-290. Abstract Full Text  

Nave, K.A. (2010) Myelination and the trophic support of long axons. Nature Reviews Neuroscience 11(4), 275-283. Abstract | Full Text (Subscription Required)

Deforges, S., Branchu, J., Biondi,O., Grondard, C., Pariset, C., Lécolle, S., Lopes, P., Vidal, P.P., Chanoine, C. and Charbonnier, F. (2009) Motor neuron survival is promoted by specific exercise in a mouse model of amyotrophic lateral sclerosis. Journal of  Physiology 587, 561-572. Abstract | Full Text

Kaspar, B.K., Frost, L.M., Christian, L., Umapathi, P. and Gage, F.H. (2005) Synergy of insulin-like growth factor-1 and exercise in amyotrophic lateral sclerosis. Annals of Neurology 57(5), 649-655. Abstract | Full Text (Subscription Required)

Kirkinezos, I.G., Hernandez, D., Bradley, W.G. and Moraes, C.T. (2003) Regular exercise is beneficial to a mouse model of amyotrophic lateral sclerosis. Annals of Neurology 53(6), 804-807. Abstract | Full Text (Subscription Required)

Carro, E., Trejo, J.L., Busiguina, S. and Torres-Aleman, I. (2001) Circulating insulin-like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy. Journal of Neuroscience 21(15), 5678-5684.  Abstract | Full Text (Subscription Required)

Carro, E., Nunez, A., Busiquina, S. and Torres-Aleman I.   (2000) Circulating Insulin-like growth factor 1 mediates effects of exercise on the brain. Journal of Neuroscience 20, 2926-2933. Abstract | Full Text (Subscription Required)

Itoh, H., Ohkuwa, T., Yamamoto, T., Sato, Y., Miyamura, M. and Naoi, M. (1998) Effects of endurance physical training on hydroxyl radical generation in rat tissues. Life Sciences 63(21), 1921-1929. Abstract | Full Text (Subscription Required)

Neeper, S.A., Góauctemez-Pinilla, F., Choi, J. and Cotman, C. (1995) Exercise and neurotrophins. Nature 373, 109. Abstract | Full Text (Subscription Required)

Further reading

Lopes de Almeida, J. P., Silvestre, R., Pinto A. C., and de Carvalho, M. (2012) Exercise and amyotrophic lateral sclerosis.  Neurological Sciences 33, 9-15. Abstract | Full Text (Subscription Required)

Ashworth, N.L., Satkunam, L.E. and Deforge, D. (2012) Treatment for spasticity in amyotrophic lateral sclerosis/motor neuron disease.  Cochrane Database of Systematic Reviews 2, CD004156.  Abstract | Full Text  (Subscription Required)

Patient Resources

Trial of Resistance and Endurance Exercise in Amyotrophic Lateral Sclerosis (ALS)  ALSTDI | Website | Contact

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Categories: Spotlight

Timeline: ALS 2011, A Year in Review

clock January 8, 2012

NeuRX DPS FDA approved ALS More Than a Power Play ALS More Than a Power Play ALS A Prion Disease ALS A Prion Disease MRI Make That A Double MRI Make That A Double Ubqln2 ALS Gene the 13th Ubqln2 ALS Gene the 13th Ubqln2 ALS Gene the 13th TAF15 Going On More Than 16 TAF15 Going On More Than 16 TAF15 Going On More Than 16 TAF15 Going On More Than 16 Empower Gathers Steam Empower Gathers Steam Empower Gathers Steam Spotlight Spotlight Spotlight antiCD40L antiCD40L antiCD40L TDP 43 Targets Emerge TDP 43 Targets Emerge TDP 43 Targets Emerge Dexpramipexole Dexpramipexole Dexpramipexole Dishing ALS Dishing ALS NP001 NP001 NP001 Silence Is Not Golden Silence Is Not Golden

With the drop of the ball, the clinks of champagne glasses and the last fireworks exploded, the year 2011 drew to a close.  Lest the auld year be forgot, ALS TODAY turns back the clock to toast the achievements and innovations in ALS in 2011.

The banner year marked the advancement of a number of cutting-edge ALS treatment strategies to phase II and phase III clinical trials and the introduction of innovative trial designs and analysis tools that promise to expedite the evaluation of these potential medicines.  Innovations in reprogramming technologies continued to push forward the possibility of personalized medicine for people with ALS.  And a new online disease registry fired up, enabling ALS researchers to unravel the genetic and environmental influences that contribute to the disease. Take a look back at ALS in 2011 by exploring this interactive timeline.

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Categories: Spotlight

Astrocytes Ignite New Therapies for ALS

clock October 28, 2011



Express delivery. Astrocytes (red) supply life's essentials to neighboring neurons (green) in the rat brain. Miriam Ascagni, San Raffaele Institute for the GE Healthcare Image Competition.

Astrocytes keep neighboring motor neurons in the central nervous system healthy by delivering essential nutrients and protective substances through regulating blood flow. But in people with ALS, growing evidence suggests that astrocytes turn against these motor neurons by triggering inflammation, injury and ultimately death.  

Researchers are now trying to understand the role of astrocytes in ALS. Recent insights into these cellular turncoats are shedding new light into disease mechanisms and inspiring new directions in drug therapies for the disease.

ALS Today's Michelle Pflumm talks to experts about astrocytes, their role in ALS and potential treatment strategies to foil their neuronal coup d'état.

 

From The Bench
A new astrocyte on the ALS block

Scientists at Uruguay's Institut Pasteur de Montevideo discover a new kind of astrocyte in rats that may contribute to ALS progression.

In Translation
Operation neuroprotection

Researchers at Johns Hopkins School of Medicine are developing a stem cell-based strategy in mice to slow or stop the progression of the disease.

Tool Time
Dishing ALS

Scientists at the Nationwide Children's Hospital recreate ALS in the laboratory dish paving the way for the discovery of new therapies for the disease.

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