Raj Mehra, PhD, and Krishna Subramanian, PhD, on Parkinson Disease Gene Therapy Mouse Studies


Mehra and Subramanian discussed preclinical safety studies with the gene therapy SLS-004 and plans for future research.

“We administered this drug not just in the disease model, but also in several safety studies [with normal mice] and looked for pathology and changes to the blood counts and to the end organs. In all these studies, what we found was that there was no safety-related risk associated with this treatment; everything from the blood values to the liver and kidneys came back as normal... Our pathologist’s comment was ‘these look like normal mice; they don't look like they've been treated with anything.’”

Seelos Therapeutics’ SLS-004 is a preclinical CRISPR-dCas9-based epigenome-editing therapy intended to reduce expression of the α-synuclein protein via a DNA-methylation approach targeted at the SNCA gene.1 In a mouse model of Parkinson disease, SLS-004's downregulation of α-synuclein production was shown to result in a substantial recovery of TH+ dopaminergic neurons in the region of the brain where SLS-004 was injected, compared to a region of the brain which received injection with a control article. Updated results from this research are expected to be presented at the International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders (AD/PD), held in Gothenburg, Sweden, March 28 to April 1, 2023.

In an interview with CGTLive, Raj Mehra, chairman and chief executive officer, Seelos Therapeutics, and Krishna Subramanian, PhD, head of non-clinical and translational science, Seelos Therapeutics, discussed some potential advantages of SLS-004, as well as the limitations of the preclinical research and plans for future study.

Image depicting modulation of SNCA with AAV-A53T + SLS-004 vector.

Image depicting modulation of SNCA with AAV-A53T + SLS-004 vector.

In particular, Mehra touched on several limitations of the data reported so far, such as the fact that behavioral changes were not examined in the treated mice, and also discussed plans for future safety research in non-human primates. Subramanian expanded on the encouraging safety data seen so far in mouse studies.

Seelos Therapeutics announces data demonstrating downregulation of alpha synuclein in an in vivo gene therapy study of SLS-004 utilizing CRISPR-dCas9 in Parkinson's disease. News release. Seelos Therapeutics. December 15, 2022. https://seelos.irpass.com/profiles/investor/NewsPrint.asp?v=6&b=2376&ID=114509&m=rl&g=1201
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