Seelos Therapeutics announced the initiation of a preclinical study of SLS-004 in Parkinson’s disease (PD) through an all-in-one lentiviral vector targeting the synuclein alpha (SNCA) gene.

Seelos is constructing a bimodular viral system harboring an endogenous alpha-synuclein (α-synuclein) transgene and inducible regulated repressive CRISPR/Cas9-unit to achieve constitutive activation and inducible suppression of PD-related pathologies.

“There has been a high level of interest in the alpha-synuclein approach to Parkinson's and beginning further work on our first gene therapy program is exciting,” said Raj Mehra, Ph.D., Chairman and CEO of Seelos. “Initiating this preclinical study earlier than expected is also very significant."

Previously, it was shown that enrichment in DNA methylation at intron 1 of the α-synuclein gene SNCA, through SLS-004, facilitated robust and precise repression of SNCA expression, which coincides with rescuing of PD-phenotypes. The SNCA gene, which encodes α-synuclein expression, has been implicated as a highly significant risk factor for PD. Accumulative evidence suggests that elevated levels of wild-type α-synuclein are causative in the pathogenesis of PD. The role of SNCA overexpression in PD pathogenesis and the need to maintain normal physiological α-synuclein protein levels emphasize the so far unmet need to develop new therapeutic strategies, such as SLS-004, targeting the regulatory mechanisms of SNCA expression. 

Alpha-synuclein (α-synuclein) is a protein which is of great interest to Parkinson's researchers because it is a major constituent of Lewy bodies and Lewy neurites, protein clumps that are the pathological hallmark of synucleinopathies, such as Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). In the several years since its discovery, alpha-synuclein has been the focus of intensive efforts by PD researchers working to definitively characterize the protein's role in Parkinson's and its potential as a target for neuroprotective therapies.