Impact case study database

Mitochondria are present in almost all animal, plant and fungal cell types, generating adenosine triphosphate (ATP), the energy currency of cells. Their role in cellular signalling is increasingly being understood and they are also key to cell death. Mutations in nuclear or mitochondrial DNA can cause life-threatening and currently incurable mitochondrial diseases which affect 1 in 4,300 adults. Mitochondrial dysfunction is a much wider phenomenon, and contributes to many common disorders in the general population, including heart disease, neurodegeneration and inflammation. Therefore, understanding the role of mitochondria in health and disease is critical to the treatment of any dysfunction but requires reliable and high fidelity tools such as the suite of molecular probes developed by Prof. Hartley. This has delivered commercial impacts in a specialised market, and contributed to a reduction in the number of animals required in research to develop therapies for common diseases.

Commercial adoption of UofG probes:

Cayman Chemical is a specialist manufacturer and supplier of biochemical reagents used primarily by pharmaceutical companies and universities life sciences research. Cayman Chemical has grown its customer base through the provision of a comprehensive portfolios of related products; they currently hold the largest portfolio of UofG mitochondria-targeted molecular probes.

“Starting in 2015, Cayman Chemical added MitoP and MitoB to our catalogue and quickly invested resources by building application notes and other web content to help promote these unique reagents. In addition, reagents were packaged both as a standalone reagent as well as value-added kit formats.” [5.1]

Cayman Chemical also provides mitochondrial hydrogen peroxide measurements as a contracted service using MitoP/MitoB. Since the company’s introduction of MitoB in March 2015, the Hartley portfolio of products has had sales in over 15 countries [text removed for publication.] Within the United States alone, customers include biopharmaceutical companies, governmental laboratories, hospitals, private institutions, clinical research organisations, research laboratories and universities.

“The portfolio of Hartley compounds available from Cayman recently expanded in 2018 with the inclusion of MitoPQ and octyl itaconate, further expanding the catalog of these reagents to researchers worldwide.” [5.1]

AbCam, a leading international supplier of life science research tools, reports that, since its inclusion in the Abcam catalogue in 2016, MitoParaquat sales have grown year-on-year, [text removed for publication] with sales across Europe, Asia and North America enabling investigations into the role of mitochondria in areas including cancer biology, parasitology and inflammation.

Non-commercial distribution:

UofG has also supplied its molecular probes to non-direct collaborators, consistent with its commitment to promote widespread use of the compound. Since August 2013, they have been supplied to 43 institutions in 17 countries through Material Transfer Agreements.

The open-access publication of synthesis protocols has enabled high-volume users to synthesise probes themselves. The Director of the USA’s National Heart, Lung, and Blood Institute noted that the ability to manufacture MitoPhotoDNP in-house has saved them USD50,000-100,000 in synthesis and development costs since 2013:

“This probe opened up a whole new area of research into the structure of the mitochondria in health and disease. Frankly, without the demonstrations that this probe provided this area of research would still be struggling to provide direct evidence of a mitochondria conductive network in striated muscle. This is likely one of the major insights into the metabolic design of muscle in the last 50 years” [5.5a].

Reducing the use of animals in research

The breeding of transgenic animals for research purposes is highly cost- and labour-intensive, requiring the breeding of many animals over and beyond those used in the experiments. The Hartley suite of mitochondrial molecular probes reduces the need for animals in research [5.5b] by avoiding the need for knock-out/knock-in of key enzymes and in the case of MitoPhotoDNP allowing for the use of autologous controls (where animals serve as their own control).

We identified 31 institutions internationally which have published research articles using Hartley’s molecular probes since 2013, including in the study of disease aetiologies such as cardiovascular disease, atherosclerosis, diabetes, cancer, neurology, metabolic disorders and aging. Of these, 19 laboratories were contacted whose research outputs used either wild-type or transgenic mammals in vivo/ex vivo; 14 responded to a survey request (74% return rate). All revealed that the UofG molecular probes had reduced the number of animals used for research by ~25% on average by changing their experimental design. This was accomplished by reducing the requirement for breeding of transgenic animals, reducing the crossbreeding of transgenic animals and facilitating the use of more robust wild-type animals.

“The use of these compounds allowed us to decipher the mechanisms in vitro and carefully plan focused in vivo studies with limited mice.” Feinberg School of Medicine, Northwestern University [5.5c]

“The use of these compounds has… offered a more streamlined approach towards the effective assessment of the oxidative state of a cell in vivo. The ability to do this without a need for the crossing to complex reporter mice has been a major step forward”. The University of Texas Southwestern Medical Center [5.5d].

[Text removed for publication.]