It needs subcutaneous administration and is considered to work by increasing regulatory T cell immunity. In addition, it might also provide antiglutamatergic and growth factor stimulating effects. 123 Link between preclinical studies are limited and contradictory, some studies found that it prolongs survival in SOD1 mutant mice, 124 while the others didn’t. 125 In a phase II trial conducted on 20 ALS individuals the drug showed safe, well tolerated benefits and influenced the immune system at the dosage studied. 126 A recent large scale Lu AA21004 double-blind, randomized placebo controlled multicenter trial on 366 ALS individuals proved safety and tolerability of glatiramer acetate at a dose of 40 mg/day but didn’t show any beneficial effect of the drug on rate of deterioration of the ALS FRS scale, or time to death, tracheostomy or permanent assisted ventilation. 127 Further studies are expected. AM 1241 Cannabinoids produce anti-inflammatory actions via cannabinoid receptor 1 and 2 and delay the progression of neuroinflammation. 128 AM 1241 is a selective agonist at the CB2 cannabinoid receptors, which can be substantially up regulated in inflamed neural tissues related to CNS disorders. 128 Animal reports on SOD1 mutant mice reported Immune system that the shots at symptom on-set can significantly increase survival. 128, 129 Nevertheless, there’s no experience with this particular compound on administration and humans probably will be parenteral. 23 Celastrol Celastrol, a pure product from southern China, has multiple effects that may be strongly related ALS. It puts powerful anti-inflammatory and anti-oxidative effects, by suppression of interleukin 1B, cyst necrosis factor, and nitric oxide. 23 Additionally it acts potently to increase expression of heat-shock proteins. 130 The oral administration prior to the onset of symptoms somewhat improved weight loss, engine performance and delayed the onset of ALS in SOD1 transgenic mice. 130 But, there’s a lack of safety and pharmacokinetic data in humans with ALS. 23 Thalidomide Thalidomide, is an old sedative and now could be used again in treating myeloma, leprosy and cachexia. It has numerous intriguing mechanisms of action for neurodegenerative Deubiquitinase inhibitors issues such as ALS, including suppression of TNF. 23 When administered orally to SOD1 mutant rats, it increased motor performance, decreased motor neuron cell death, and dramatically prolonged expected life. 131 But a small open label study found no improvement in development of the disease. Additionally, therapy with thalidomide was associated with many side effects. 132 Further clinical trials are nevertheless underway. 24 Due to thalidomide s unwanted effects, lenalidomide may offer a better alternative. 131, 133 Nordihydroguaiaretic acid Nordihydroguaiaretic acid Iis a lipoxygenase inhibitor that improves glutamate uptake in engine neuronal cells and inhibits TNF activation of microglia134. 135 A current animal research on SOD1 transgenic mice found that nordihydroguaiaretic acid extends survival and slowed motor dysfunction.