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.

Stable core crosslinked poly (amino-acid) based particles as biodegradable delivery materials

RCSI and DCU have developed a scalable emulsion polymerisation process for the synthesis of cross-linked nanoparticles based on α-amino acids. The nanoparticles are expected to be fully biodegradable, non-toxic and amenable to a wide range of functionalisation via standard peptide chemistry. This materials platform is thus highly adaptable for various applications in the pharmaceutical, cosmetic and personal care sectors.

ChemoGel: A thermoresponsive drug delivery platform for intratumoral delivery of chemotherapeutics in pancreatic cancer

ChemoGel is a unique, thermoresponsive, hydrogel drug delivery platform for the site-specific delivery and sustained release of chemotherapeutics at solid tumour sites. ChemoGel is a platform technology which enables the sustained local delivery of chemotherapeutics agents and is intended for use in the chemical ablation of solid tumours alone or in conjunction with other treatment approaches. The technology is now in pre-clinical development at RCSI for its first clinical indication in pancreatic cancer.

Disease-modifying treatment for epilepsy

Researchers at RCSI's Department of Physiology & Medical Physics discovered that levels of microRNA-134 are abnormally high in human epilepsy and silencing microRNA-134 expression in vivo using a microRNA-134 antagomir (‘AntmiR134’) rendered mice refractory to both seizures and hippocampal injury caused by status epilepticus (Nature Medicine 18, 1087 to 1094, 2012). Subsequent research by the RCSI research group has shown the antagomirs work in other seizure models and, most recently, has shown that a single systemic injection of AntmiR134 (30 mg/kg) resulted in: (a) a significant reduction in the total number of epileptic seizures; and (b) the total time spent in seizures.

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.

InnovoSep – A novel method of treating or preventing sepsis

Sepsis is a major challenge in the intensive care unit, where it is one of the leading causes of death. It arises unpredictability and can progress rapidly. Staphylococcus aureus and Escherichia coli are among the most common microorganisms isolated from sepsis patients. The Cardiovascular Infection Research Group in RCSI has demonstrated that cilengitide prevents both S. aureus and E. coli from binding to the endothelium thus inhibiting early signal generation that results in endothelial cell dysfunction in sepsis.

STAR polypeptides – Versatile reagents for RNA drug delivery

Star-polymers are a new class of polymer architecture which consist of linear arms radiating from a central core. Novel Star-polypeptides discovered at RCSI have been demonstrated to have superior transfection and delivery efficacy compared to current commercially available technologies. Therapeutic applications include the delivery of DNA plasmids, siRNA and miRNA to cells.

FKBPL: Novel target for obesity and metabolic syndrome

The obesity pharmaceutical market is projected to grow from $407 million in 2012 to $8.4 billion by 2022. 40-70% of inter-individual variability in BMI is attributable to genetic factors. Although treatment strategies are available, the side-effects associated with their use necessitates development of novel therapies. FKBPL is a promising novel drug target for obesity and metabolic syndrome and researchers at RCSI have developed FKBPL peptide mimetics and gene therapies as therapeutic options.

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).

STAR polypeptides – Versatile therapeutics for respiratory, cardiac, anti-infective and regenerative medicine

Star-polymers are a new class of polymer architecture which consist of linear arms radiating from a central core. Novel Star-polypeptides discovered at RCSI have been demonstrated to have superior transfection and delivery efficacy compared to current commercially available technologies. Therapeutic applications include the delivery of DNA plasmids, siRNA, miRNA, proteins and small molecules. The polypeptides have also been demonstrated to have intrinsic angiogenic, osteogenic and antimicrobial properties.

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.