The Center for Proteomic and Genomic Research, a new facility based in Cape Town, South Africa, has recently begun several studies with the goal of developing array-based theranostics and diagnostics for allergies and asthma, according to a CPGR official.
Reinhard Hiller, director of the CPGR, told BioArray News recently that the center opened its doors earlier this year. Among other projects, the center has been studying asthma using an allergen chip platform Hiller helped develop as an R&D director at Vienna-based VBC Genomics, where he worked before coming to Cape Town to lead the CPGR.
The center is funded through a ZAR 20 million (US $2.8 million) grant from Cape Biotech Trust and Plant Bio, biotech regional innovation centers that dispense government funds to help grow South Africa’s biotech resources. According to Hiller, the first projects are part of CPGR’s long-term objective to establish a high-throughput biology research facility that serves the needs of the life science and biotech communities in South Africa.
As a core facility, Hiller said that CPGR is mainly engaging in joint research initiatives with the scientific community who gain access to “cutting-edge technology and the respective expertise” through the CPGR.
“Based on a strong interest expressed by clincians in South Africa, a key focus of research is on asthma,” he said. So far the CPGR has been involved in “simple disease marker monitoring, or allergen-specific antibody monitoring, in children suffering from Type-1 allergy-related asthma,” Hiller said. “What we are really looking for is antibody patterns and if there is something that is important to understand for treatment.”
Hiller is using the antibody arrays to study immunoglobulin E, an antibody frequently associated with hypersensitivity, and immunoglobulin G, an antibody resposible for adaptive immune response, in parallel in patients to discover protective IgG antibodies.
“Sometimes you can detect IgGs against an allergen in patients, when then there’s no IgE or there’s very low IgE,” Hiller said. “This means that they have a protective IgG, which is very good. So to understand this you will know that the treatment is going to be very different for these patients,” he added.
Together with leading allergy experts in South Africa, Hiller is currently preparing two studies based on this methodology: one studying allergic reactions to latex and another studying patients with occupational asthma. In the latex study, which is scheduled to begin next year, the CPGR is using its antibody arrays to profile IgG/IgE patterns in a cohort of 100 individuals.
“What we are trying to establish here is antibody patterns in response to immune therapy that could in turn lead to the development of theranostic tests, for example predicting efficacy or side-effects of treatment,” Hiller said.
In a few months, the CPGR will also begin studying patients with occupational asthma — respiratory problems that are attributable to an individual’s work environment. Hiller said that the occupational asthma study will involve between 400 and 600 patients with the goal of “trying to develop and improve better diagnostic algorithms to help these patients and then also implement preventive measures.”
“It’s really translational as we are aiming at an immediate clinical and practical use of the results generated in the study,” he said. “It’s more of a molecular phenotyping study or a molecular diagnostics study where we want to understand the underlying antigen-specific IgE patterns in these patients.”
In the scheme of array-based diagnostics development, allergy chips barely register. Many companies, like Agendia, Pathwork Diagnostics, and CombiMatrix Molecular Diagnostics, have instead decided to develop tests for cancer diagnosis or prognosis, while others have taken advantage of the multiplexing capabilities of arrays to develop chips for identifying congenital birth defects or carriers of genetic diseases, like cystic fibrosis.
According to Hiller, the reason for his ongoing research into allergy is based on a belief that there is a unique niche in array-based research that is overlooked despite the prevalence of allergy and asthma in developed countries.
“This is a disease that is pretty much neglected in developing countries in comparison to other diseases, like infectious diseases for example,” Hiller said. “What we see today is that allergy is an interesting disease because nobody knows why it is spreading and developing so quickly,” he said.
“One thing for sure is that as soon as the population changes from rural to urban, the frequency of these diseases skyrockets. And this is what is happening in Africa because there’s large-scale urbanization,” he added.
Hiller pointed to a recently published study that found the prevalence of asthma in Africa to be high. In 2007, the researchers found the prevalence of asthma in Cape Town to be 20 percent, while in Nairobi, Kenya, it is 18 percent, and in France’s Reunion Island, located off the coast of Madagascar, it is nearly 22 percent [Ait-Khaled, et al. Prevalence of symptoms of asthma, rhinitis and eczema in 13- to 14-year-old children in Africa: the International Study of Asthma and Allergies in Childhood Phase III. Allergy. 2007 Mar;62(3):247-58.]
Hiller said that the rationale for allergen studies in Africa is three-fold. Firstly, because of the prevalence of diseases like asthma in North America and Europe, any diagnostic breakthroughs in South Africa would have international significance. Secondly, Hiller said that due to insufficient diagnosis, “chronic respiratory diseases like asthma are already posing a considerable burden on health care systems in Africa” — a fact that makes his work more urgent.
“One thing for sure is that as soon as the population changes from rural to urban, the frequency of these diseases skyrockets.”
Another factor that makes the South African work relevant is the fact that the CPGR can draw on a diverse population of cohorts. In a country where the motto is “unity in diversity,” Hiller has access to cohorts of northern European, African, and South Asian descent.
“You have different populations with many different symptoms,” he said. “So when we develop a diagnostic test, then it very easily can be used all over the world because we have weighed it against many different populations at this point. That’s one of the benefits of working in South Africa.”
Tools of the Trade
To access the samples for its studies, CPGR will rely on an informal network of clinicians and researchers in South Africa. Also, through the center’s contacts with South African companies such as Synexa Life Sciences and BioClones it can establish public-private partnerships “that speed up conversion of scientific findings into products with practical and commercial value,” Hiller said.
CPGR’s primary allergy-related tool is the Immuno Solid-phase Allergen Chip Hiller helped develop at VBC Genomics.
Hiller said he plans to add allergens to ISAC to meet the demand of different projects. “For example, we want to develop seafood allergen microarrays because seafood allergy is very important, especially in those countries where seafood is a major component of their diet,” Hiller said. “So, together with collaborators in South Africa and South East Asia, amongst others, there is ongoing work where we ... use this array and we are adding new content.”
To avoid IP issues, Hiller will order custom ISAC arrays from VBC for CPGR’s various projects, he said.
In addition to its allergen studies Hiller said that a good proportion of CPGR’s projects are related to infectious disease. This is an immediate focus for the center, which aims to enable “improved biomedical research related to key African diseases such as tuberculosis, AIDS, malaria and cancer. However, CPGR is also engaged in plant-related projects, such as for the identification of pathogen-resistant traits in key crops such as maize,” he said.
CPGR’s overall objective is to stimulate the South African biotech community, and to do that it maintains a significant core facility in Cape Town that offers Affymetrix GeneChips, arrays for Agilent ChIP-on-Chip applications, Exiqon Mircury LNA microarrays, and Operon custom-expression profiling arrays, as well as a variety of platforms for proteomic research, including equipment for protein microarray development and mass spectrometry-based protein characterization and profiling.
According to Hiller, CPGR aims to serve the existing biotech market in South Africa, which he admits is comparatively small, as well as to facilitate the achievement of more life sciences-relevant research and stimulate biotech sector activity.
“I have been employed to make sure that we can build up this kind of resource [for] the scientific community because it has been identified as a gap in growing the biotech sector in South Africa,” he said.
“Eventually what we are supposed to do is stimulate the biotech economy, by helping people develop new IP, by increasing the output of scientific publications, by spinning out companies and by supporting existing companies,” said Hiller.