Innovative Trials are passionate about ensuring our diverse population is adequately represented within medical research. Whether it is wanting to see more people from underrepresented communities choosing science as a career and pushing for greater patient diversity in clinical trials or focusing on what we are doing internally to celebrate and promote equality and diversity, this month we celebrate Sickle Cell. So far the Equality, Diversity, and Inclusion Committee at Innovative Trials has written blogs to raise awareness surrounding several illnesses, their effects, and treatments such as World Lupus Day, Malaria, Pride Month, Sickle Cell, Endometriosis , Pancreatic Cancer Awareness Month , Parent Mental Health Day, International Day of Women and Girls in Science and International Childhood Cancer Day.

Hemoglobin is a protein found in red blood cells of most vertebrates, which is responsible for the delivery of oxygen to tissues and organs. A healthy red blood cell is shaped like a donut, with the flat center increasing the cell’s surface area to help with oxygen diffusion. The shape of red blood cells can change depending on a variety of factors and this affects their ability to function effectively (Diez-Silva et al, 2010). Sickle Cell Disease (SCD) is a hereditary blood condition characterized by abnormal hemoglobin, which impairs the ability of red blood cells to effectively transport oxygen around the body. The ‘sickle-shaped’ cells, first discovered in 1910, tend to cluster and block blood vessels, which can lead to further health complications (John Hopkins Medicine, 2019). These complications can include (Borhade et al, 2024):

  • Vaso-occlusive crisis – Blockages in the bloodstream caused by sickle red blood cells
  • Spleen crisis – Sickled red blood cells block the passage of blood out of the spleen, leading to tissue death from oxygen deprivation (infarction) 
  • Aplastic crisis – Bone marrow stops making new red blood cells, leading to rapidly dropping hemoglobin levels  
  • Acute chest syndrome – Can follow vaso-occlusive crises and low oxygen levels across the body (hypoxia), due to hypoventilation (increased carbon dioxide levels) or fat embolisms
  • Hemolytic crisis – Destruction of red blood cells occurs at a rate faster than new ones are created, leading to a deficit
  • Osteonecrosis – Sickled red blood cells cause reduced oxygen levels to the point of bone death
  • Nephropathy – Deterioration of kidney function, caused by reduced oxygen function and hypertension 
  • Strokes – Sickled red blood cells cause oxygen and nutrient deprivation of the brain
  • Girdle syndrome – Vaso-occlusion in the lungs, liver, and mesentery (membrane that holds the intestines in place)

Rare Diseases

Rare diseases are classified by low individual prevalence. They can be characterized by high levels of variance, even among patients nominally diagnosed with the exact same condition. This leads to difficulty in fully understanding a disease, correctly diagnosing, providing care to patients, and also developing effective treatments (Eurordis, 2024).

Looking at rare diseases on a global level (Lancet, 2024):

  • There are over 7000 distinct rare diseases, with each affecting 1 in 2000 people within a World Health Organization (WHO) region, at most 
  • 300 million people are estimated to be living with a rare disease
  • 80% of these diseases have a genetic cause
  • 95% lack approved treatment
  • The time for accurate diagnosis is 4-8 years, affecting those in need of urgent treatment

Sickle Cell Disease (SCD) and Sickle Cell Trait (SCT)

SCD is a genetic disorder, inherited as an autosomal recessive trait. Despite its perceived frequency, its actual occurrence is estimated at 8 million people worldwide. The number with Sickle Cell Trait (SCT) rises to over 300 million, though. Patients with SCT can still suffer from sickle cell anemia, but there is a reduced occurrence of the various kinds of vaso-occlusive crises (Ashrobi et al, 2024).

Innovative Trials Experience With Rare Diseases

Innovative Trials have provided patient recruitment and retention support for over 33 successfully completed rare disease studies. These have included: Amyotrophic Lateral Sclerosis (ALS), Acute Myeloid Leukemia (AML), Ankylosing Spondylitis, Duchenne Muscular Dystrophy (DMD), Hemophilia, Lupus, Multiple System Atrophy and Thrombocytopenia. Innovative Trials have supported 4 Sickle Cell clinical trials; 3 in Site & Patient Educational Materials Development, and 1 for 1:1 In-country Recruitment Coaching & Site Support. 

This experience, along with significant research undertaken for service proposals, has resulted in a solid foundation of knowledge that would be an asset for recruitment on future projects. Looking up SCD on ClinicalTrials.gov, there are 1058 studies on record, with 529 completed and 45 not yet recruiting. There are 192 studies that are currently recruiting. Examining those studies further: 40 are in Phase I, 60 are in Phase II, 18 are in Phase III, and 4 in Phase IV.  There are 42 studies that look at getting a better understanding of life with SCD. These look at a variety of aspects:

  • Medical diagnosis methods
  • Care and family planning
  • Pain tolerance
  • Physical therapies
  • Managing childhood development
  • Secondary complications and their prevention

Summary

Opportunities for involvement in SCD studies are present and with Innovative Trials’ experience working in supporting rare disease studies, the potential for a positive impact on recruitment for a study are significant. There is a significant amount of research taking place globally and a challenge for many will be finding the right patients with each rare disease. There is a good spread of research looking at observing patients and others that seek to provide effective interventions.  As a genetic disorder, SCD will be among the many that would benefit from any further breakthroughs made in genetic research. Casgevy and Lyfgenia are 2 gene therapies approved by the USA Food and Drug Administration (FDA) in recent years. Both are treatments that are intended as a single delivery treatment that eliminates the condition. Casgevy uses a gene-editing tool, abbreviated to ‘CRISPR’, to reactivate the production of fetal hemoglobin, which can counter the amount of abnormal hemoglobin caused by SCD. Lyfgenia uses a viral envelope to deliver a gene that produces regular hemoglobin into patients. Both treatments are being observed through long-term follow-up to determine their actual effectiveness. The development of such treatments are promising and give hope for new research being able to fully manage the number of challenges created by SCD (MacMillan, 2023).  

References