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Lest we forget, sickle cell disease not yet fully curable despite a century of trials

Thursday July 02 2020
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Even though studies of new technologies such as gene editing and whether they can replace bone marrow transplant—the only known definitive cure for sickle cell disease—are in early stages, the technologies are also offering much needed probes for understanding SCD, thus informing identification of new drug targets. FILE PHOTO | NMG

By BERNHARDS OGUTU

Sickle cell disease was first brought to light in America around 1910. The first recorded patient was a young medical student of African descent from Grenada named Walter Clement Noel.
It was not until 40 years later that it was determined that sickle cell disease (SCD) was due to a hereditary phenomenon affecting the haemoglobin chains in the red blood cells.
There have been few treatment modalities ever since. The only pharmacological treatment for SCD has been hydroxyurea till the second decade of the 21st century.
Even then, its use had started in 1995 but as a repurposed drug.

Treatment options

The first cure of SCD that occurred in 1984 through bone marrow transplant was also incidental as the patient was being treated for leukaemia.

This extols the neglect for this disease in all aspects of research, pathogenesis, diagnosis and treatment options.

Be that as it may, SCD diagnosis has greatly benefited from technological advances, from basic microscopy to genome sequencing.

The designation of the orphan disease status to SCD by regulatory agencies, such as US Food and Drug Administration, spurred interest in product development for therapeutic agents in the treatment of the disease.

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As we look into the future of research, we need to be cognisant of the fact that we are dealing with a disease viewed as affecting a small segment of the population.
Prevalence of SCD in African countries is about one to two per cent of the population with the carrier status of above 20 per cent.

For example, in the Lake Victoria Basin, the prevalence of SCD carriers is about 25 per cent. The mortality rate in most African countries is still high mainly because of lack of established programmes 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.

Such an understanding will enhance development of strategies to mitigate the burden of disease in next generations and formulation of appropriate policies for the management of SCD in different regions.

To this end, there are pan-African networks of research groups involved in developing 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.

Bone marrow transplants

There are several clinical trials of existing drugs being repurposed for the management of SCD and new molecules that have shown promising results in its treatment.

Even though studies of new technologies such as gene editing and whether they can replace bone marrow transplant—the only known definitive cure for sickle cell disease—are in early stages, the technologies are also offering much needed probes for understanding SCD, thus informing identification of new drug targets.

However, since SCD is a multisystem disease, collaboration is necessary for a number of the treatments will have to be used in combination as has happened with chronic diseases.

Broken health systems

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.

Thus pharma companies, academia, philanthropists and other disease consortia will have to work with researchers from SCD endemic countries to mine existing large pool of chemical and technological database to identify promising interventions.

To harness this framework, we will need well characterised cohorts of people living with SCD to understand what interventions are likely to improve their quality of life and even provide cure.

Community screening

To get well characterised Sickle cell disease cohorts we need comprehensive care centres linked through a functional programme 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 programme has to be embedded in a strong diagnostic framework for newborn screening to enable early diagnosis and establish catch up community screening to identify those who are carriers and at risk of having children with SCD in future.

In a setting like Kenya with communities known to have high prevalence of Sickle cell disease, 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, there is a need operational research to inform what will work best for a particular community prior to their deployment.

Dr Ogutu is a senior researcher at Kenya Medical Research Institute.

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