The Sickle Cell Chronicles: A New Hope

Last weeks news of a new potential cure for Sickle Cell Anaemia and Thalassaemia demands attention.

MHRA authorises world-first gene therapy that aims to cure sickle-cell disease and transfusion dependent B-thalassaemia

https://www.gov.uk/government/news/mhra-authorises-world-first-gene-therapy-that-aims-to-cure-sickle-cell-disease-and-transfusion-dependent-thalassemia

I feel like Rafiki in Lion King when he learns Simba is Alive.

But for me the news is learning ‘Hope’ is Alive

Lets not get too carried away

Last weekend I attended a regional Sickle Cell and Thalassaemia patient conference. I listened to Haematology Consultants from across the Country discuss Gene editing therapy in more detail.

Casgevy (exagamglogene autotemcel) (Excel) is based on the innovative gene-editing tool CRISPR, which won its inventors the Nobel Prize in 2020.

As much as I love geeking out about how cool the gene-editing mechanism of action is, the most important thing by far is the effect it will have on peoples lives.

The reality of receiving curative treatment myself has been top of mind since last weekend.

Its only when I think about living free of Sickle Cell that I realise just how much it restricts me.

Its how I imagine a Ostrich would react to finding treatment which enabled it to fly.

Even though imagining this happening lights me up with hope, a dark shadow looms in the corner of my mind whispering;

‘There’s no way you’ll ever get it, your life is not worth a million dollars’.

NICE (National Institute for Health and Care Excellence) is the UKs department for recommending the use of new treatments.

Before Casgevy can be given to patients it has to be reviewed by NICE and they have to recommend eligibility criteria to guide local NHS bodies. Given the cost of the therapy this is likely to be quite strict.

The question inescapable in my mind then is how much is the quality of life of a sickle cell patient worth?

How Gene Editing with Casgevy works

I’ll try to keep this as simple as possible.

Fetal Haemoglobin is present in babies in the womb and after birth, it does a good job of carrying oxygen in the red blood cells without any problems.

However after about 3 months of age the production of Fetal Haemoglobin is switched off as normal Adult Haemoglobin takes over its role.

Unfortunately in Sickle Cell the Adult Haemoglobin starts to cause sickling of the red blood cells leading to all the problems associated with the disease.

Up until this point the Fetal Haemoglobin had been present in a high enough percentage in the red cells to prevent sickling.

The gene BCL11A is responsible for turning off the production of Fetal Haemoglobin in babies.

What gene editing does is cut the BCL11A gene out of the DNA.

With the BCL11A gene no longer present the body starts to produce Fetal Haemoglobin again.

With Fetal Haemoglobin once again present in the Red Blood Cells it is able to maintain the shape of the Red Blood Cells and prevent sickling.

The Red Blood Cells of patients in the clinical trials have been found to contain around 50% Fetal Haemoglobin. This is the same level of normal Haemoglobin that sickle cell carriers have. So far the majority of treated patients have remained free from crisis.

Current Treatments for Sickle Cell

1)Hydroxyurea

This is recommended for people who have recurrent hospital admissions for acute chest syndrome or acute painful crisis. It also works by raising the level of Fetal Haemoglobin.

Acute chest syndrome is a form of lung injury which is severe and life threatening. Its associated with severe sickle cell crisis and infection particularly in early childhood.

To my knowledge I’ve never had it. Around 30% of people with sickle cell will have one episode in their lifetime and half of those will have recurrent episodes.

2)Elective Blood Transfusions

In some patients the level of sickling of the red blood cells is so severe that the sickle cells wreak havoc on a number of different organs. They are also destroyed much faster than they are produced resulting in severe anaemia.

In this situation a blood transfusion may be required to flush normal blood through the body and bring relief from sickle cell crisis and organ damage for a few months at a time.

3)Surgery

Avascular necrosis occurs when the bones are starved of oxygen for so long that areas of bone with particularly poor blood supply die and cause chronic pain.

Surgery may be needed to relieve pain, replace joints and treat bone infections of the dead bone.

4)Stem Cell Transplantation

This is the only cure currently available for sickle cell disease and is only offered to children and some Adults with severe sickle cell disease.

Stem cells are special cells produced by the bone marrow that have the ability to turn into different types of blood cells.

Healthy stem cells are donated by a close family member such as a sibling that has a similar tissue type and transferred to the patient. This is called an allogenic transplant.

The process involves destroying unhealthy blood cells with chemotherapy and then replacing them with the healthy donor stem cells which go on to produce healthy red blood cells.

The main issues:

Gene Editing the practical process

1. Collect stem cells from the patients own bone marrow, so no need to find a matched donor.

2. Treating the collected stem cells with gene editing

3. Strong chemotherapy to kill all the previous stem cells in the body.

4. Returning the treated stem cells into the body

5. The new stem cells produce fetal haemoglobin and the person is cured.

Theres no risk of Graft Versus Host Disease because the treated stem cells belong to the patient so will know they are homies from the same body.

Gene-editing is a better option for relatively healthy people than Bone Marrow Transplant

1. Their stem cells need to be collected over a period of months. It may take 3-4 sessions to harvest enough stem cells to treat.

2. The intensive Chemo and side effects are better tolerated.

3. Pre-existing organ damage related to sickle cell cannot be reversed by Gene-editing. This means long term it has the most potential to benefit patients who don’t already have irreversible organ damage.

What does it mean for me?

From the current sickle cell treatment list above you can see roughly the severity of the patients go up from 1-4. The likelihood is that only the most severely affected patients would qualify for Casgevy, with the caveat that they have no irreversible organ damage.

I’ve taken Hydroxyurea since 2015. Before I started it I was having 2-3 sickle cell crisis a year and had 2 hospital admissions over a 3 year period.

This was probably the worst it had ever been and it appeared to be triggered by the stress of being a junior doctor.

Since then I have a blood test every 3 months to monitor my white blood cell count. Hydroxyurea can lower white bloods cells which are important for fighting infections.

The dose has to balance not lowering my white bloods cells too much but still be strong enough to prevent me having sickle cell crises.

Since I’ve taken the Hydroxyurea I’ve still had crises but I’ve been able to manage them all at home with moderate opiod tramadol.

Quality of Life?

Living on hydroxyurea isn’t ideal. I stay healthy because I’m disciplined but if I wasn’t I’d be a lot worse off.

If you offered me the chance to be able to experience true freedom I would take it in a heart beat.

When you’ve lived with sickle cell your whole life you take for granted adaptations you’ve made to survive.

You get used to a quality of life that would be considered restrictive by normal people. You accept the futility of complaining about what can’t be changed and just get on with it.

I’m simply saying that how I rate my quality of life doesn’t correlate with the reality of it.

In reality if I was cured of sickle cell my life would change significantly and its difficult to conceptualise that for someone looking from the outside seeing an apparently healthy person.

Another potential eligibilty issue is the number of recorded hospital visits with sickle crisis. I’ve not had any hospital admissions for 8 years because I’ve worked my ass off to stay out.

It’s difficult not to imagine a situation where I have to prove my eligibility by reverting back to my past lifestyle to intentionally provoke sickle cell crisis.

Although this would also expose my organs to potential damage and reduce my health further.

For example the other weekend I could have played in an Alumni basketball game. I drove almost 2 hours back to Nottingham but when I got there I decided not to play. I saw the intensity everyone was running and I knew there would be a guaranteed crisis waiting for me hydroxyurea or not.

I’ve really just repressed a lot of the sadness I felt for the loss of activities and experiences that bring me the best quality of life.

Its difficult because I hear how it sounds in my head ‘who am I to live my best life when others are struggling way more than me?’

I’ve always practiced this type of gratitude but I’ve realised recently 3 things:

1. It’s a negative attitude to have, you should aim to be the best that you can be not the best that others can be.

2. Your success doesn’t mean other peoples failure.  

3. Your elevation doesn’t mean others are lowered. It just means you’re in a better position to help them up.

I know that in time the treatment will cheapen and may be more widely available but I don’t want to wait.

I feel like at this point along my personal growth journey my confidence and outlook has improved so much. Its like I know I can do anything I set my mind to but at the same time I can’t.

Sickle cell hangs over me like the sword of damocles.

I’m ready now, I’ve started climbing Mount Everest and I want to reach the top before I freeze to death.

This treatment would really help me and many others like myself so its important now more than ever to:

• Keep talking about it

• Write to the sickle cell society about lived experiences.

• Write to the All-Party Parliamentary Group for Sickle Cell and Thalassaemia

• Get them to discuss it and put pressure on the government.

Even if I don’t get it I want as many people as possible to get it that are worse off than me.

Thank you for reading

Lewis