BOSTON– Latus Bio Inc. has reported new preclinical findings showing that its engineered gene delivery technology improved targeting of cells in the brain, spinal cord and kidneys, potentially addressing longstanding challenges in developing gene therapies for neurological and kidney disorders.
The biotechnology company presented the findings at the European Society of Gene and Cell Therapy’s 33rd Annual Congress, held October 27-30 in Hamburg, Germany.
The research focused on modified adeno-associated virus (AAV) capsids, which serve as delivery vehicles for transporting genetic material into specific cells.
The company said its experimental capsid variants demonstrated improved delivery efficiency and tissue targeting compared with AAV9, a commonly used viral vector in gene therapy development.
One of the experimental variants, known as AAV-PN, was designed to deliver genetic material broadly to neurons throughout the brain and spinal cord while minimizing unwanted gene expression in other organs.
In studies involving adult nonhuman primates, researchers administered AAV-PN at low doses directly into the brain’s ventricular system.
The results showed widespread distribution throughout the central nervous system, with approximately 40% to 60% of neurons in the cerebral cortex receiving the genetic material.
The capsid also demonstrated delivery to as many as 40% of motor neurons in the spinal cord.
According to Latus Bio, the engineered variant achieved substantially higher gene expression in the central nervous system than AAV9 administered through either intracerebroventricular or intravenous delivery.
The experimental capsid also showed reduced off-target expression in peripheral tissues, including the liver and dorsal root ganglia, structures associated with sensory nerve cells.
The findings suggest that engineered capsids could potentially improve the precision of gene therapies targeting neurological conditions while reducing unwanted exposure in other tissues.
Latus Bio also presented results involving a separate group of engineered AAV capsids designed specifically for kidney diseases.
The company’s AAV-Kd variants demonstrated increased delivery of genetic material to cells within the kidneys following low-dose intravenous administration in nonhuman primates.
One variant, AAV-Kd-1, successfully delivered genetic material to approximately 80% of the glomeruli in both kidneys.
Glomeruli are microscopic structures responsible for filtering blood and removing waste products from the body.
The study also found that AAV-Kd-1 achieved more than 30% transduction in several important kidney cell types, including podocytes, glomerular endothelial cells and mesangial cells.
In addition, the variant reached approximately 30% of proximal tubular cells and demonstrated more than twice the delivery efficiency of AAV9 in distal tubules and collecting ducts.
The company said additional engineered kidney-targeting variants are being evaluated for their ability to improve delivery to kidney tissue while limiting exposure to the liver.
Such advances could help address a major obstacle in kidney gene therapy, where delivering sufficient genetic material to disease-relevant cells has remained challenging.
Beyond its capsid engineering platform, Latus Bio presented additional preclinical findings from its investigational gene therapy programs for Huntington’s disease and CLN2 Batten disease.
Its experimental Huntington’s disease treatment, LTS-201, combines an engineered capsid called AAV-DB-3 with an artificial microRNA designed to reduce production of the MSH3 protein.
MSH3 plays a role in DNA mismatch repair and has been linked to genetic instability associated with the onset and progression of Huntington’s disease.
The treatment is designed to target specific neurons in the striatum and cerebral cortex that are affected by the progressive neurological disorder.
In nonhuman primate studies, LTS-201 reduced MSH3 messenger RNA levels by as much as 94% in more than 90% of targeted medium spiny neurons.
Researchers also observed dose-dependent reductions in genetic instability in a mouse model of Huntington’s disease.
The company presented a computational model developed using human data to estimate how reducing MSH3 activity could potentially delay clinical disease progression.
The model connects the degree of MSH3 suppression and the proportion of targeted neurons with projected delays in disease progression.
The findings were also published in the scientific journal Nature Communications.
Latus Bio additionally presented preclinical safety findings for LTS-101, its experimental gene therapy for CLN2 Batten disease, a rare inherited neurological disorder.
The treatment uses the company’s engineered Ep+ capsid to deliver a functional gene encoding tripeptidyl peptidase 1 (TPP1), an enzyme deficient in patients with CLN2 Batten disease.
In a nonhuman primate toxicology study conducted under Good Laboratory Practice standards, LTS-101 was generally well tolerated through six months following administration.
The treatment also maintained TPP1 protein levels in cerebrospinal fluid that the company believes could have therapeutic potential.
LTS-101 has received Fast Track, Orphan Drug and Rare Pediatric Disease designations from the U.S. Food and Drug Administration.
The FDA has also cleared the company’s Investigational New Drug application for LTS-101, allowing the treatment to advance into clinical testing.
Latus Bio is developing its engineered AAV technology to improve gene delivery across multiple tissues, with a particular focus on neurological and rare genetic diseases.
While the preclinical findings demonstrate improvements in gene delivery and biological activity, additional clinical research will be necessary to determine whether the experimental treatments are safe and effective in humans.
