Israeli company, hospital partner to develop ASOs for rare diseases

Collaboration has goal of 'propelling' genetic treatments for patients in need

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Skip Therapeutics is teaming up with the Sheba Medical Center in Israel to develop antisense oligonucleotides (ASOs), a type of therapy that can change a given gene’s activity, for rare diseases with a genetic basis.

ASOs can be tailored to address specific genetic mutations, offering a bespoke treatment option for people with rare or ultra-rare diseases, such as aromatic L-amino acid decarboxylase (AADC) deficiency, for which often there are few or no effective treatments.

Sheba will give Skip access to its patient mutation database, which has been cleared of personal information. In turn, the Israel-based company will use its proprietary computational platform to check if ASOs can be designed to work around specific mutations and offer a suitable treatment strategy.

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Goal is finding treatments for AADC deficiency and other rare disease

“We are pleased to enter into a collaboration agreement with the world-renowned Sheba Medical Center for the development of ASO-based treatments for rare genetic diseases,” Ariel Feiglin, PhD, Skip’s chief scientific officer, said in a company press release.

“We look forward to propelling gene therapy forward as a result of this exciting collaboration,” said Dan Dominissini, PhD, the deputy director of the Center for Cancer Research and director of the Hematology Laboratory at Sheba Medical Center.

“Skip Therapeutics’ novel computational engine will [enable] us not only to determine the most appropriate therapeutic design for a given genetic disease, but also to directly identify treatable patient populations, thereby maximizing efficiency and minimizing costs,” Dominissini added.

Like many other rare diseases, AADC deficiency is caused by mutations in a single gene that result in deficient levels of a protein, or in the production of a faulty version of that protein.

“However, the small number of patients for each [rare genetic] disease has hindered development of dedicated treatments,” Feiglin said.

To work around this limitation, scientists have explored the use of ASOs, lab-made RNA or DNA molecules designed to bind to specific messenger RNA (mRNA) molecules, or to the intermediate molecules derived from DNA that guide protein production.

ASOs can be used to correct the function of a gene, either by enhancing or suppressing protein production or by determining which version of the resulting protein is produced by targeting a natural process called splicing.

Splicing is the process by which noncoding parts of a gene are cut from the mRNA molecule, and the remaining coding sections are joined together to define the information that will be translated into a protein.

“Recent advancements in RNA-therapeutics offer an expanded molecular toolkit that can be deployed rapidly and at relatively low costs to restore protein function of mutated genes,” Feiglin said.

ASO-based therapies have already been approved for rare genetic diseases such as Duchenne muscular dystrophy and spinal muscular atrophy, with benefits seen in others, including Batten disease.

ASOs provide “exciting possibilities of drug development for small patient [groups] and eventually even for single patients,” Feiglin said. “To effectively realize these possibilities, it is necessary to incorporate computational tools in the developmental process, and we believe that our computational approach will enable an effective and rapid development of ASO-based treatments.”

Skip, which started up at the FutuRx biotechnology accelerator, has identified potential ASOs for eye and lung diseases that are being tested in preclinical studies with patient-derived cells.