研發肌萎縮性脊髓側索硬化症之藥物

@ Introduction

Recently, there is no cure drug for ALS disease. The treatments of ALS focus on slowing the progression of disease or providing temporary relief of disease discomfort. For examples, MIROCALS (Modifying Immune Response and Outcomes in ALS) project plan recruits 216 participants to test a protein molecule against interleukin-2 (IL-2) for slowing down the advance of the disease. The other drug-GM604, is a peptide drug that regulates signaling pathways of embryonic growth factors and can modulate hundreds of ALS related genes. GM604 has neuroprotective effects in MND patients through intravenous injection. Although, GM604 is safe in people with MND disease through Phase I and Phase II clinical trials. But reportedly there was no difference in ALSFRS-R ratings between patients receiving GM604 and control placebo. Thereof searching a potential peptide/protein drug would be a great demand in the motor neuron disease.

The AAV-based gene therapy for ALS is being developed in preclinical stage, the intravenous injection of rAAVrh10-miR-SOD1 in ALS mice (SOD1 G93A mutant) can extend the survival and delay the disease onset compared to control group; the intravenous injection of AAV9-DOK7 can improve NMJ innervation, nerve terminal area and prolong the survival in ALS mice compared to control group. Although, the treatment of ALS is extensively investigated, there are two drugs approved by FDA so far. The Riluzole (RILUTEK) is the first medication
approved by the FDA, and prolongs patient life span by a few months. In 2017, Edaravone (RADICAVA) was approved by FDA to enhance the ALSFRS-R
scores but without survival benefit on ALS patients, testifying to a strong need for new treatment strategies.