Seelos Set to Begin Animal Studies for SLS-007 Using Gene Therapy Approach

Seelos Therapeutics will begin animal studies to test a gene therapy approach to deliver its investigational candidate SLS-007 for Parkinson’s disease.

SLS-007, originally developed by scientists at the University of California, Los Angeles, is intended to lessen the aggregation, or clumping, of alpha-synuclein protein — a major component of the Lewy bodies found in Parkinson’s patients.

The investigational therapy consists of a family of peptide blockers that specifically target a central region of alpha-synuclein called the non-amyloid component core, which is particularly prone to aggregation.

In preclinical studies, SLS-007 was able to slow disease progression, including stopping alpha-synuclein propagation and seeding — a process in which a “seed” provides the template for the aggregation of normal protein into clumps. This occurred when scientists used fibril preparations and alpha-synuclein seeds collected from patients with Parkinson’s or Lewy body dementia.

Now, the researchers at Seelos will test a modified, harmless form of a virus, called an adeno-associated virus, or AAV, as a vehicle to deliver SLS-007. In preparation, the company currently is producing the viral vectors and preparing the animals for its preclinical study.

“Identifying the AAV vector as the optimal route of systemic administration of SLS-007 may ultimately yield a convenient one-time delivery of the peptides,” Raj Mehra, PhD, chairman and CEO of Seelos, said in a press release.

“This is a novel method of viral delivery that has been a collaboration between our R&D team and key opinion leaders that, if successful, could be a major advancement in the field,” Mehra said.

The aim of the animal studies is to test the best route of administration, establish the pharmacokinetic and pharmacodynamic profiles of SLS-007, and assess parameters of target engagement to alpha-synuclein. In pharmacokinetics, researchers evaluate the movement of a compound into, through, and out of the body —essentially how the body affects a medicine. Pharmacodynamics determines the interactions between the body and a compound.

“The study will include measurements of several key biomarkers that will assess the extent of alpha-synuclein (α-synuclein) aggregates expression in key target areas of the brain, such as the forebrain and the substantia nigra,” said Tim Whitaker, MD, Seelos’ head of research and development.

“These outcomes will help determine key target engagement and set the stage for our next steps with the program,” he added.

The results from these studies, namely delivery and target engagement, are expected in the second half of this year.

Seelos also is developing SLS-004, its other candidate to treat Parkinson’s disease. SLS-004 uses another modified, harmless form of a virus, known as a lentivirus, to deliver an enzyme called DNA methyltransferase 3A. This targets a particular region of the SCNA gene, which provides the instructions for making alpha-synuclein, and limits the protein’s production.