Therapeutics

Highly selective inhibitors of HDAC6 for the treatment of cancers and neurodegenerative disease

Researchers in RCSI and the Dana-Farber Cancer Institute have discovered a novel structural class of highly-selective HDAC6 inhibitors. These patented small molecules have a unique non-hydroxamic acid chemical structure and are >250-fold selective over the other HDACs. The lead compound BAS-2 has been shown to inhibit glycolysis in Triple Negative Breast Cancer Cells – a unique vulnerability independent of the mitochondrial apoptosis pathway which is one of the key drivers of chemoresistance.

Novel epigenetic biomarkers and targets for metastatic colorectal cancer

Researchers at RCSI have developed a novel biomarker panel to identify patients with colorectal cancer who are at high risk of developing metastatic disease. The team are seeking industry partners to co-develop this predictive test and also to leverage the extensive epigenetic dataset to identify new drug targets in mCRC. Biomarker-led early intervention with directed therapies may help to improve outcomes for this high-risk group.

ADAM22 and LGI1 mimetic peptide: A complete solution as a directed therapeutic strategy for endocrine related tumour metastasis

ADAM22 is a novel therapeutic target for metastatic disease, with a peptide drug based on its natural ligand, LGI1. The technology compromises of a clinically validated and commercially ready immunohistochemical assay for the detection of ADAM22 in breast cancer tissue to be utilised as (i) as a biomarker for predicting the metastatic potential of breast tumours in endocrine treated breast cancer patients and (ii) as a companion diagnostic for a novel therapeutic (LGI1) to treat metastatic ER positive breast cancer.

This technology is being commercialised by RCSI spin-out company Probmet.

Rapid Acting Pharmaceutical for Infectious Disease (RAPID)

A key hallmark of sepsis is loss of epithelial and endothelial barrier integrity thus facilitating fluid to leak into tissues that results in organ failure, shock and death. To date, dysfunction of the endothelial/epithelial barrier has been untreatable. Inthelia Therapeutics is developing a novel small molecule drug, cilengitide, that stabilises the epithelial and endothelial barrier. Inthelia has granted patents to protect use of cilengitide in sepsis and others filed for COVID-19.

This technology is being commercialised by RCSI spin-out company Inthelia Therapeutics.

STARMAT – A versatile star polypeptide platform for oligonucleotide drug delivery

Star-polymers are a new class of polymer architecture which consist of linear arms radiating from a central core. Novel star polypeptide-based vectors discovered at RCSI have superior transfection and delivery efficacy compared to current commercially available technologies coupled with improved stability, biocompatibility and immunogenicity. Therapeutic applications include the targeted delivery of DNA plasmids, siRNA mRNA and miRNA and incorporation into bioactive scaffolds and medical devices.

This technology is being commercialised by RCSI spin-out company StarMAT.

FKBPL: Novel target for obesity and metabolic syndrome

RCSI researchers have discovered a novel target, FKBPL, which regulates energy expenditure, and have shown that obesity and type 2 diabetes (T2D) develop when levels of this protein are low in mice and humans. Proof of concept data demonstrates that therapeutic delivery of FKBPL improves T2D and promotes weight loss in mice. The aim is to develop a novel mRNA-FKBPL nanoparticle therapeutic and to pre-select patients who are suitable for treatment based on their serum FKBPL levels.

This technology is being commercialised by RCSI emerging spin-out company Imuphile Therapeutics.

A novel therapeutic approach to restore haemostasis in individuals with haemophilia

RCSI has developed a novel therapeutic approach to restore haemostasis in individuals with haemophilia by the inhibition of the initiation and activity of anticoagulant pathways mediated by activated protein C (APC).

Modulating macrophage plasticity for the treatment of disease

Researchers in RCSI have discovered that enhancing the expression of a particular enzyme maintains macrophages in an anti-inflammatory and tissue regenerative state. They have developed a target site blocker which up-regulates the expression of this enzyme and can be incorporated within biocompatible nanoparticles for targeted drug delivery. This disruptive technology can be exploited as a therapy for a range of autoimmune, inflammatory and neurological diseases associated with an inflammatory burden mediated by macrophages.

Novel RNA therapeutic targeting sodium channelopathies

Genetic epilepsies caused by mutations to voltage-gated sodium channels do not currently have adequate treatment options. These diseases begin in the early years of life, with infants suffering severe seizures as well as developmental deficits such as ASD. RCSI researchers are developing a new and innovative treatment which selectively restores the function of specific voltage-gated sodium channel genes.