This roundup of recent amyotrophic lateral sclerosis (ALS) research and clinical trials news includes:
Orphan drug status in Europe for NurOwn
The European Commission on July 29, 2013, granted orphan drug designation for NurOwn, for the treatment of ALS in the European Union. Orphan drug designation provides pharmaceutical companies with financial incentives to develop a medicine for a rare disease. The stem cell therapy, under development by BrainStorm Cell Therapeutics, previously received orphan drug designation from the U.S. Food and Drug Administration (FDA) in 2011. BrainStorm announced in an Aug. 1, 2013, press release preliminary safety data from its phase 2a trial of NurOwn in people with ALS at the Hadassah Medical Center in Jerusalem, Israel. The company said the experimental treatment was well-tolerated and no serious events were observed in the second group of trial participants.
Higher ALS risk in northern New England?
Study results indicate areas of high ALS incidence (the number of new cases of ALS identified each year) within the northern New England states of New Hampshire, Vermont and Maine, reports a research team led by Elijah W. Stommel at Dartmouth-Hitchcock Medical Center in Lebanon, N.H. The team identified 11 ALS clusters in four distinct areas, where the number of people with ALS was higher than the expected incidence for the disease in the United States. Further analysis is needed to determine if any correlation exists between these areas and potential environmental risk factors. The findings were published online July 23, 2013, in Muscle and Nerve.
ALS-affected cerebrospinal fluid in rats
A research team led by T.R. Raju at the National Institute of Mental Health and Neurosciences in Kamataka, India, reports that infusing cerebrospinal fluid from people with sporadic ALS into the brains of rats was associated with increased activity (hyperexcitability) of motor neurons, the muscle-controlling nerve cells that are lost in ALS, as well as structural changes in the brain that led to motor dysfunction. The findings, which were published online July 31, 2013, in the Journal of Neural Transmission, support the idea that changes in motor neuron excitability play a role in ALS.
K3E mutation in the SOD1 gene
In a study conducted in people with ALS who were of Polish and Japanese descent, findings show that the ALS-causing K3E mutation in the superoxide dismutase 1 (SOD1) gene is associated with a slowly-progressing, limb-onset form of ALS. In study participants with the K3E mutation, average age of onset was 54 years; average survival time was approximately 8.5 years; and age of death ranged from 45 years to 77 years. The team — led by Hubert Kwiecinski, with members in Poland and Japan — published its findings online July 30, 2013 in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration.
Blood DNA test to determine C9ORF72-associated ALS
It's possible that a disease-causing mutation present only in central nervous system (brain and spinal cord) tissue could be missed if it were screened for in a blood DNA sample. However, findings from an Australian study involving 38 people with sporadic ALS suggest that it is unlikely there would be evidence of an ALS-associated C9ORF72 mutation in central nervous system tissue without simultaneous evidence of the mutation being found in blood. The findings suggest that a routine blood DNA test likely is sufficient to make a diagnosis of C9ORF72-associated ALS. The team, led by Bing Yu at Royal Prince Alfred Hospital and Sydney Medical School, published its findings online July 19, 2013, in PLoS One. See Can ALS-Associated C9ORF72 Repeat Expansions Be Diagnosed on a Blood DNA Test Alone? Note: Genetic testing using a blood sample is available for C9ORF72-associated ALS and C9ORF72-associated frontotemporal dementia (a spectrum of cognitive and behavioral problems). For help obtaining genetic testing or interpreting test results, contact your local MDA clinic or MDA/ALS center.
Cellular model for sporadic ALS
In disease research, the research “model” — whether a mouse or cells in a petri dish — must accurately represent the disease being studied. To that end, a research team reports that it generated induced pluripotent stem cells (iPSCs) from cells that were taken from people with sporadic ALS (ALS that occurs with no known family history) and from unaffected individuals. The iPSCs — adult cells that have been genetically reprogrammed back to a stem-cell-like state — were then coaxed into becoming motor neurons, the muscle-controlling nerve cells that are lost in ALS. When the ALS and non-ALS iPSCs were compared, the cells derived from people with ALS showed ALS-associated abnormalities. The team notes that such iPSC-derived motor neurons could provide an accurate cellular model for the disease. The findings were published online July 25, 2013, in Molecular and Cellular Neuroscience.
Progesterone exerts neuroprotective effect in mice
Results from a study conducted in South Korea show that treatment with the hormone progesterone was associated with reduced nerve cell death, slower progression of motor dysfunction and longer average life span in a research mouse model of ALS. The apparent benefits in the mice may have resulted from activation in the spinal cord of a cellular cleanup and disposal process called autophagy. The research team, led by Jae-Young Koh at the Ulsan College of Medicine in Seoul, published its findings online July 26, 2013, in Neurobiology of Disease.
Emotion processing may predict ALS- FTD
The ability to process emotions refers to such skills as accurately interpreting others' facial expressions, tone of voice and gestures; recognizing sincerity or sarcasm; and analyzing contextual clues to determining truth or deceit in conversation. Results from a study conducted in Australia show that processing of emotions is significantly impaired in people with frontotemporal dementia (FTD) and with ALS-FTD. (FTD causes a spectrum of cognitive and behavioral problems; ALS-FTD refers to the simultaneous occurrence of both ALS and FTD.) By contrast, emotion processing was unaffected in people with ALS who did not have dementia.
Performance on emotion processing tasks may provide a useful clinical tool in identifying those with early FTD-ALS, noted the research team led by John Hodges at the University of South Wales, Sydney. The team published its findings online July 29, 2013, in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.
TDP43 in ALS and FTD
Jonathan Janssens and Christine Van Broeckhoven, both at the University of Antwerp (Belgium), highlight and discuss the current understanding of the role abnormal TDP43 protein plays in neurodegeneration. The authors address different disease pathways associated with abnormal TDP43 protein, the lack of effective therapies to cure or delay ALS and FTD disease progression, the importance of animal models that mimic ALS and FTD in gaining novel insights into TDP43 biology, and advances in stem cell technology that may create new opportunities to study TDP43-related neurodegeneration and therapeutic strategies. Read the full review, published online July 29, 2013, in Human Molecular Genetics: Pathological Mechanisms Underlying TDP43 Driven Neurodegeneration in FTLD-ALS Spectrum Disorders.
Environmental factors and ALS
A research team based at Second University of Naples (Italy) reviewed the current understanding of toxic factors that may contribute to the development of ALS, with emphasis on the potential roles of cyanobacteria (also known as blue-green algae), heavy metals and pesticides. The team published its review online July 24, 2013, in the International Journal of Molecular Sciences. See Exposure to Environmental Toxicants and Pathogenesis of Amyotrophic Lateral Sclerosis: State of the Art and Research Perspectives.