(Medical Xpress)—A team led by Dr. Alex Parker, a professor of pathology and cellular biology and a researcher at the University of Montreal Hospital Research Centre (CRCHUM), has identified an important therapeutic target for alleviating the symptoms of Lou Gehrig's disease, also known as amyotrophic lateral sclerosis (ALS), and other related neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease.
In a study published in the online version of Neurobiology of Disease, the team both confirmed the importance of this new target as well as a series of compounds that can be used to attenuate the dysregulation of one of the important cellular processes that lead to neuronal dysfunction and ultimately to brain cell death.
Although scientists are unclear about causes of ALS, they have made headway in identifying the cellular process potentially implicated in disease onset and progression. One such process which has attracted researcher interest involves the endoplasmic reticulum (ER), a component of cells that plays an important role in maintaining cell health. In collaboration with Dr. Pierre Drapeau at the University of Montreal and using worm and zebrafish models of ALS, Parker's team not only confirmed that incapacitated ER leads to the motor neuron death typical of ALS, but also identified a series of compounds that alleviate the fatal consequences of defective ER.
"Since Riluzole, the one approved treatment compound for treating ALS, only has a modest effect on slowing disease progression, we set out to test a number of other compounds, and in so doing we discovered that they work by compensating for defective ER" explains Dr Parker. The compounds in question, Methylene blue, Salubrinal, Guanabenz and Phenazine, were each tested individually and in different combinations.
With the exception of Phenazine, these compounds have known benefits for treating neurodegenerative diseases. Parker and his team showed that each of these compounds reduces paralysis and neurodegeneration and that each acts on different parts of the ER pathway to achieve neuroprotection. More importantly, the researchers found that using these compounds in different combinations can enhance their therapeutic effects.
"These results are quite encouraging," says Dr Parker, "and have given us a much better understanding of ER's role in ALS as well as showing the way for improved treatments". Parker's team plans to test and confirm these findings with more complex animal models, a necessary step in developing medication that can be of benefit to human beings.
About amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis is an adult onset neurodegenerative disorder characterized by a progressive and selective loss of motor neurons in the motor cortex, the brainstem and the spinal cord, leading to rapidly progressing weakness, muscle atrophy, muscle spasticity and difficulty speaking, swallowing, and breathing. Most ALS patients die from respiratory failure. The disease, for which there is no known cure, affects about 1-3 people in 100,000. The etiology of ALS is composed of both genetic and environmental factors and its origins remain unknown for most cases. Its clinical development is extremely variable.
Explore further: Potential new drug target in Lou Gehrig's disease
"Pharmacological reduction of ER stress protects against TDP-43 neuronal toxicity in vivo" was published on April 5, 2013 in the online version of Neurobiology of Diseases. An abstract of the article can be viewed on Pubmed: www.ncbi.nlm.nih.gov/pubmed/23567652.