Preclinical Study of SLS-004, Potential Parkinson’s Gene Therapy, Starting

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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PD GENEration study

Seelos Therapeutics announced it is beginning, earlier than expected, a preclinical study into its investigational gene therapy candidate for Parkinson’s disease called SLS-004.

The exact nature of this early research work was not detailed in a press release.

Nerve cell damage in Parkinson’s is caused by the buildup of toxic forms of the alpha-synuclein protein, and resulting clumps of misfolded proteins known as Lewy bodies. These toxic aggregates damage and eventually kill nerve cells — called dopaminergic neurons — in a region of the brain that regulates muscle movement and coordination.

The loss of these nerve cells leads to a shortage of dopamine, a neurotransmitter (chemical messenger) that allows nerve cells to communicate and helps to regulate movement.

Seelos reports that SLS-004 uses a modified, harmless form of a virus, known as a lentivirus, to deliver an enzyme called DNA methyltransferase 3A to promote the methylation of a particular region of the gene coding for alpha-synuclein, called SCNA.

Methylation — the addition of specific chemical (methyl) groups that sit on top of a particular region within DNA — is a way to regulate the activity of a gene mainly by “switching” it off.

This system is based on CRISPR-dCas9 gene editing technology, and intends to fine-tune the activity of the SNCA gene to lower the production of alpha-synuclein.

“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,” Raj Mehra, PhD, chairman and CEO of Seelos, said in the release.

“Initiating this preclinical study earlier than expected is also very significant,” he added.

Earlier preclinical studies investigated SLS-004’s efficacy when delivered to dopaminergic neurons derived from stem cells donated by a Parkinson’s patient. Results showed that the gene therapy effectively altered the activity of the SCNA gene, leading to a lower levels of alpha-synuclein.

It also was seen to possibly protect against disease-related changes, including the production of harmful reactive oxygen species (ROS), and to improve cell viability.

Seelos is also testing SLS-007, another Parkinson’s gene therapy candidate that aims to lessen the aggregation of alpha-synuclein in patients.

SLS-007 is made of a family of peptide blockers that specifically target a central region of alpha-synuclein, called the non-amyloid component core, that is particularly prone to aggregation.

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