New Research Will Test CLR01 ‘Molecular Tweezer’ in Sanfilippo Models

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by Marisa Wexler |

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A newly funded research study will test whether an investigational therapy dubbed a “molecular tweezer” — officially called CLR01 — might ease symptoms of Sanfilippo syndrome in preclinical models.

The project is co-funded by the Cure Sanfilippo Foundation, the Australian Sanfilippo Children’s Foundation, and the HANDS consortium of patient groups, scientists, and clinicians.

“The hope is that with promising results, we can move to a clinical trial for treating children with CLR01,” Cara O’Neill, MD, chief science officer at the Cure Sanfilippo Foundation, said in a press release.

Leading the new project under this research grant is Alessandro Fraldi, PhD, a professor at CEINGE – Advanced Biotechnology, in Naples, Italy.

In prior work, Fraldi and other researchers demonstrated that certain proteins — called amyloid proteins — form aggregates, or clumps, in the brains of mice with Sanfilippo type A. Then, they tested the effect of treatment with CLR01 in these mice.

Described by the researchers as a “molecular tweezer,” CLR01 is a broad-spectrum inhibitor of protein self-assembly. In other words, it stops a variety of different proteins from clumping up.

In the type A mouse model, treatment with CLR01 prevented the formation of such amyloid protein aggregates. It also worked to normalize other biological processes in the brain that are typically impaired in Sanfilippo syndrome, such as lowering brain inflammation. CLR01 treatment also reduced neurodegeneration — the death of brain cells — and eased symptoms, such as lessening memory impairment, in these mice.

Fraldi and his colleagues have published their previous findings in the journals Molecular Therapy and Frontiers in Molecular Neuroscience.

The researchers noted that treatment with CLR01 was generally more effective when given to mice in the early disease stages. It conferred little benefit to animals with more advanced disease.

In the new project, Fraldi and other researchers will build on the prior findings by testing whether similar benefits can be achieved with CLR01 treatment in mice with other types of Sanfilippo syndrome. Specifically, the team will investigate whether CLR01 is effective in Sanfilippo type B and type C.

The scientists also will test whether higher doses and longer treatment might lead to more benefits in older mice with advanced disease.

In addition, the researchers will compare treatment with CLR01 with treatment with gene therapy, and will assess the possibility of combining the two. Sanfilippo is caused by mutations in specific genes, making it a candidate for gene therapy. Such therapy is a treatment strategy that aims to deliver a non-mutated version of the gene to the body’s cells.