Nneka Uchea Smith
- Sep 17, 2023
- 6 min read

Research - why we still need to fight!

Sickle cell disorders are one of the most under researched hereditary disease groups and even the research there has been tends to focus on HbSS (what some know as sickle cell anaemia). The disorder affects over 15,000 people in the UK, which is more than how many people affected by cystic fibrosis (~11,000).

Where we were

Findings from a research study the US in the 1990s was the first to demonstrate that those with sickle cell had fewer painful crises and blood transfusions.[1] In 1995, the national heart, lung and blood institute (US) found that it reduced the number of painful episodes by 50% in severely affected adults with sickle cell. [2] However, hydroxycarbamide is a chemotherapy treatment and belongs to a group of treatments known as anti-metabolites. Anti-metbolites stop cells making and repairing DNA [3] and so, this means it reduces the cell replication of the defective haemoglobin. This means, there is an increase in fetal haemoglobin (the red cells that are seen in babies) it can also make the blood thick by reducing the white cell count. [4]

This all comes with lots of issues;

1. it has a huge exclusion criteria (those with HbSC and other forms do not have as many crises);

- you have had three or more hospital admissions in the last 12 months for a sickle cell crisis

- have regular crises at home affecting your work or normal daily life

- have had two or more chest crises

2. it is difficult to predict who will benefit from hydroxicarbamide

3. it tends to only be suitable to those with HbSS or HbS/Beta forms of sickle cell disorders

4. it takes up to 3 months to see the benefits (in that time, you need to have constant monitoring of your blood count to ensure your haemoglobin/white cell count etc do not drop too low)

5. it can reduce the white count and platelet count to low levels and this may increase risk of infection and bleeding

For over 20 years, other than blood transfusions and pain medication, if you were excluded from hydroxycarbimide, you had limited treatment options. The standard advice was to:

- drink plenty of fluids to avoid dehydration

- wear warm clothing to stop you getting cold

- avoid sudden temperature changes, such as swimming in cold water [5]

Where we are now

In 2020, Adakveo (official Novartis brand name), known as crizanlizumab in the UK), was the first targeted sickle cell therapy which aimed to prevention of recurrent vaso-occlusive crises (VOCs) to be made available for use in Europe.[6] So, in Jan 2020 I began the trail. I was the second patient in the whole of the UK (and we believe that I am the longest UK participant in the trial.

Criz is a P-selectin medication, P-selectin (a protien) plays a role in the multicellular interaction that lead to VOCs and therefore this medication would prevent VOCs and have other potential benefits. In 2022, after initially being regected by the National Institute for Health and Care Excellence (NICE) and lots lobbying and parlimentary debates the medication was given to a patient on the NHS. It was broadcast with headlines such as "Crizanlizumab is the latest in a line of NHS drugs deals that is seeing patients benefitting from new cutting-edge treatments..." [7]

More recently though, Novartis discussing the changes and improvements to their study, the European Medical Agency (EMA) have formally withdrawn the license for Criz. I was the patient representative at this and at the sharing my story of success with Criz over the last 3 years with the EMA and with the Medicines and Healthcare products Regulatory Agency (UK). These meetings were frustrating and sad. Having to deal with inaccuracies, poor choices/use of language and the lack of knowledge with those who ultimately have the power to decide how my life will progresses is hard and it did take a lot out of me. I was honoured to do it, and to represent a whole community of sickle cell warriors in the UK, but personally, having to share what life is like with those who have to avoid empathy and stay rational and pragmatic in their decision making, was emotionally draining.

Where we are going

Since then, there has been many more clinical drug trials and therapy treatments being trialed and researched. These are a combination of aiming to prevent/reduce VOCs or aiming to prevent the red cells sickling. [8] The sickle cell society have a list of active clinical trials happening in the UK at present. [9]

Science is evolving and with it, our techniques, and the ways that we target disorders that previously have not had much progress. Currently, laboratory grown red blood cells are being transfused into volunteers in a clinical trial that would revolutionise treatments further. [10]

In 2022, the University of York was awarded £2.3 million by the Bill & Melinda Gates Foundation towards their research into stem cell gene therapy for sickle cell. This was a collaborative project linking with those in Cambridge, Boston, Tanzania and Uganda. [11]

As we continue on the research journey, it is important to remember the gaps experienced by sickle cell warriors with regards to the inconsistency of care across the NHS. The reasons given for this is the limited understanding of the condition as reported. [12]

There is still room for growth

In 2021, an All-Parliamentary Group published a report [13] detailing the issues patients with sickle cell disease experience and it highlighted that ‘awareness of sickle cell among healthcare professionals is low, with sickle cell patients regularly having to educate healthcare professionals about the basics of their condition at times of significant pain and distress’. When presenting the report, the former chair of the APPG who led the report, Pat McFadden MP said "a pattern of many years of sub-standard care, stigmatisation and lack of prioritisation which have resulted in sickle cell patients losing trust in the healthcare system that is there to help them, feeling scared to access hospitals, expecting poor treatment from some of those who are supposed to care for them and fearing that it is only a matter of time until they encounter serious care failings".

Key findings from the inquiry included:

- evidence of sub-standard care for sickle cell patients admitted to general wards or attending Accident & Emergency (A&E) departments (including a widespread lack of adherence to national care standards)

- low awareness of sickle cell among healthcare professionals and clear examples of inadequate training and insufficient investment in sickle cell care

- frequent reports of negative attitudes towards sickle cell patients and a weight of the evidence suggests that such attitudes are often underpinned by racism [13]

I fed into this report and some of the stories were heartbreaking, we forget how embroiled access, inclusion and level of healthcare is when is comes to socio-economic and education status. Access to healthcare should not depend on your postcode, whether you went to university or what your household income is.

Even the smallest stone makes ripples

As I highlighted in my first sickle cell awareness blog, "don't get me wrong, we have a long way to go to improve our health inequalities and the standards of care for our warriors, but let us highlight a few of the positive things..."

- when I was in school (early/mid 90s), the predicted age of survival was 40 for people with sickle cell...

- we hadn't realised how other haemoglobinopathies can combine with the known haemoglobin S (HbS) to form the various genotypes in the sickle cell disorder groups. - you may have heard people refer to sickle cell aneamia etc this was used to refer to HbSS we now have formally identified other types; HbSC (my type) HbS/α-Thal, HbSD, HbSE, HbSO-Arab, HbSβ0 + Alpha Thal and many more...

- we have patient information groups, many of which have been part of the All-Parliamentary Group report