Abstract：
:Neurotrophic factors as candidates for ALS therapeutics have previously been studied in the context of attempts to slow disease progression. For a variety of reasons, clinical trials of neurotrophic factors have failed to show efficacy in ALS patients. Previous studies in Parkinson's Disease (PD) models have shown promise with the use of recombinant adeno-associated virus serotype-2 (rAAV2)-neurturin (NRTN) [AAV2-NRTN] providing neuroprotection and behavioral improvements in preclinical models which subsequently resulted in several clinical studies in patients with PD. Given that this neurotrophic compound has not been studied in the context of ALS, we conducted a study of AAV2-NRTN to assess the preclinical safety, tolerability, biodistribution, and efficacy of this compound in an ALS mouse model. SOD1G93A mice were injected with AAV2-NRTN intraspinally at several doses into the cervical spinal cord at 60 days of age. NRTN expression was noted in motor neurons (MNs) of the targeted cervical spinal cord as well as in their neuromuscular junction projections but not in the lumbar spinal cord, which was not targeted. Neuropathologically, a dose-dependent neuroprotective effect was seen in cervical MNs and neuromuscular junctions that was reflected in a slowing of forelimb grip strength decline. As expected, this neuroprotection was found to be focal and was not seen beyond the immediate region of injection. Overall, there were no increases in morbidity, changes in serum chemistries or blood counts and no cases of drug-related mortality. Because there is a broad clinical experience for this compound, these data provide evidence to support further investigation of AAV2-NRTN as a potential ALS therapeutic.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Gross SK,Shim BS,Bartus RT,Deaver D,McEachin Z,Bétourné A,Boulis NM,Maragakis NJdoi
10.1016/j.expneurol.2019.113091subject
Has Abstractpub_date
2020-01-01 00:00:00pages
113091eissn
0014-4886issn
1090-2430pii
S0014-4886(19)30238-9journal_volume
323pub_type
杂志文章abstract：:Recent work has indicated that photobiomodulation (PBM) may beneficially alter the pathological status of several neurological disorders, although the mechanism currently remains unclear. The current study was designed to investigate the beneficial effect of PBM on behavioral deficits and neurogenesis in a photothromb...
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