Development and evaluation of novel foetal Haemoglobin Inducers

Key Inventor

Dr Jim Vadolas

Summary of the opportunity

Researchers at the Murdoch Childrens Research Institute have identified numerous lead compounds for the treatment of β-thalassaemia using a novel cell-based assay. The lead compounds are already approved by the FDA for the treatment of other diseases. The novel cell-based assay is a simple red/green read-out, quantifiable using FACS analysis of suspension cells.

The Problem / Target Market

There will be approx > 900,000 annual births of HbE/β βo Thalassaemia

• The current treatment for thalassaemia involves regular blood transfusions every 3-4 weeks combined with daily intravenous iron chelation.
• If untreated, thalassaemia is a lethal disease.
• Increased levels of γ-globin (the major subunit of foetal haemoglobin) expression can ameliorate the clinical symptoms associated with β-thalassaemia and sickle cell disease.

Technology, State of Development and Competitive Edge

The Cell & Gene Therapy Group at the Murdoch Childrens Research Institute has developed a novel genomic dual-reporter assay system to identify and evaluate factors which may influence globin gene expression and elucidate further our understanding of the globin switching process. Constructs were used to generate stable human erythroleukaemic (HEL) and murine erythroleukaemic (MEL) cell lines. These genomic reporter assays closely resemble the γ- and β-globin gene expression in embryonic/foetal (HEL) or adult (MEL) environments, allowing rapid and simultaneous analysis of both globin genes' expression at specific developmental stages. Current results show that these genomic reporter assays have applications in the identification and evaluation of new chemical inducers of HbF, as well as in the study of globin gene regulation in particular the γ- to β-globin switch.

Using the dual fluorescence γ-globin cellular reporter system described above, a chemical compound library consisting of 2000 mainly Food and Drug Administration (FDA) approved drugs has been screened. The HTS identified numerous compounds that induced expression from the γ-globin promoter in 1o and 2o screens. Importantly, one class of these compounds induced γ-globin promoter activity in vitro at much higher levels than hydroxyurea and butyrate (the current 'gold standard' in thalassaemia treatment). This family of novel inducers of HbF contain FDA approved drugs for use in humans to treat unrelated conditions and are amenable to further medicinal chemistry alterations.
The researchers have also generated a humanized mouse model that could be used as an in vivo testing platform.

Nature of the Deal

The Murdoch Childrens Research Institute is looking to identify and secure a licensing partner in the pharmaceutical or biotechnology industry to contribute to the development of the technology. Murdoch Childrens Research Institute is seeking an up-front license fee and an annual royalty for the use and application of the technology by the licensee. Royalties would also be payable in the event the licensee wishes to sub-licence the use of the technology for an agreed purpose.