Research needed for sickle cell disease

In Summary

• In the research landscape for a neglected disease there is need to have a high appetite for opportunistic adaptation of new technologies and therapeutic agents being used in other diseases and other scientific advances.

• This will require a strong collaboration between the researchers in the SCD form endemic countries.

Kenya Medical Research Institute.
Kenya Medical Research Institute.
Image: FILE

Sickle cell disease (SCD) is an old disease with a characteristic geographical distribution that mirrors malaria endemicity before its elimination in Europe and the Americas and parts of Asia and Middle East. By virtue of sickle cell disease being a hereditary disorder with globalization SCD disease is now found in every territory of the world. However, SCD has remained a disease of neglected persons and this is depicted from the early times when it was first described in medical literature. The disease was first described around 1910 in America in young medical student from Grenada named Walter Clement Noel of African heritage.

Like many other diseases prevalent in Africa, SCD have been known to occur in Africa for over 5000 years based on the names that describe the disease in many languages and recently through genetic modeling. A reference in time from the fist description it took almost 40 years before it was determinedthat SCD was caused by a hereditary phenomenon affecting the heamoglobin chains in the red blood cells. As with any globally distributed disease, the morbidity and mortality in SCD has a dichotomous disparity that mirrors the status of the health system in a country.

As a neglected disease much of the 100 years since the first description of SCD there have been very few treatment modalities available. The onlypharmacological treatment for SCD has been hydroxyurea till the second decade of the 21st century, however, it’s use started in 1995 but as repurposed drug. The first cure of SCD that occurred in 1984 through bone marrow transplant was also incidental as the patient was being treated of leukaemia using bone marrow transplant. This extols the neglect for this disease in all aspects of such as research concerning pathogenesis, diagnosis and treatment options. However, the diagnosis has greatly benefited from technological advances from basic microscopy to whole genome sequencing currently enabling further characterization of the disease.

It the designation of the orphan disease status for SCD by regulatory agencies namely FDA and EMA has seen a spur in interest by players in product developmentfor therapeutic agents in the treatment of the disease. Therefore, as we look into the future of research in SCD disease we need to be cognoscente of the fact that we are dealing with disease viewed as affecting a small segment of the population. The disease is prevalent in Africa where thousands of children are born yearly with SCD. It is estimated that the prevalence of SCD in African countries is about 1-2% of the population with the carrier status of > 20%. A case in point is the lake Victoria basin where the prevalence of SCD carriers is about 25%.

The mortality rate is still very high in the childhood in most African countries mainly because of lack of  established programs for the management of SCD. There is a renewed interest in understanding the magnitude of SCD disease in sub-Saharan Africa with the aim of improving the survival and quality of life for those with SCD. The better understanding of the burden of the disease will also enhance development of strategies to mitigate burden of disease in the next generations and formulation of appropriate policies for the management of SCD in different regions. In this context there are pan African networks of research groups to develop databases across different countries that will create large cohorts of people living with SCD to support the development of new interventions in the treatment of SCD.

There are several clinical trials of existing drugs being repurposed for the management of SCD and new molecules that have shown promising results in treatment of SCD. In the recent times there is emergence biologics namely monoclonal antibodies in the treatment of SCD and their impact will be proven with time as they get deployed in large population of people with SCD. SCD is benefiting from new technologies such as gene editing and their import is yet to be seen as most studies are in early stages and whether they may replace bone marrow transplant, the only known definitive cure for SCD. The new technologies such as gene editing are also offering much needed probes for understanding  SCD in greater detail thus informing identification of new drug targets.

However, SCD being a multisystem disease none of the treatments will be a silver bullet and a number of the treatments will have to be used in combination and this calls for greater collaboration. The evaluation of promising drugs in combination creates another hurdle in the product development pathway but is the only solution to optimal care for those with the disease. Combination therapy has worked well in the treatment of a number of chronic diseases. SCD disease being a neglected entity any product development program should have a access plan in focus from conception if impact is achieved in those who really need it.

In the research landscape for a neglected disease there is need to have a high appetite for opportunistic adaptation of new technologies and therapeutic agents being used in other diseases and other scientific advances. This will require a strong collaboration between the researchers in the SCD form endemic countries and biotech, pharma companies, academia, philanthropists and other disease consortia to be able to mine existing large pool of chemical and technological database to identify promising interventions.

To be able to harness this framework for development of new interventions we will need to have well characterized cohorts of people living with SCD to understand what interventions are likely to improve their quality of life and even provide cure. To be able to have well characterized SCD cohorts we need to have comprehensive care centres linked through a functional program that provides a holistic care for the persons living with SCD. This is not a responsibility of the governments alone, but all the stakeholders interested in the welfare of persons living with SCD.

The program has to be embedded in a very strong diagnostic framework for newborn screening to enable early diagnosis and also establish catch up community screening to identify those who are careers and at risk of having children with SCD in future to help the make appropriate matrimonial commitments. In a setting like Kenya where there communities known the have high prevalence of SCD, community screening as strategy that will ultimately lead to reduction of the SCD burden is of essence. As more interventions become available for the management of SCD, prior to their deployment there is need operational research to inform what will work best for a particular community.

Holistic management of SCD in Kenya is an urgent need and this has to underpinned within a robust national program based on research. The research has to be need driven poised to improve the quality of life for persons living with SCD.

Dr. Bernhards Ogutu is a senior researcher at KEMRI