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Gene & Protein in Disease Sickle cell disease’s journey

there is an abrogation of hypoxia-induced vaso-occlusion Academy of Pediatricians, all SCD children below 5 years
in SCD patients. Crizanlizumab was approved by the of age are required to get a penicillin prophylaxis against
FDA in 2019 as a treatment for vaso-occlusive pain in life-threatening pneumococcal infection. Children above
SCD patients aged 16 or above following the multicenter 5 years of age who have undergone splenectomy need to
clinical trial SUSTAIN. It has been shown to decrease continue this prophylaxis. Penicillin prophylaxis is also
the frequency of pain crises in SCD, with no significant recommended in adults who have undergone splenectomy
change in hemolytic parameters. In a systematic review of as well as in SCD females who have conceived. As a
the SUSTAIN trial, post hoc studies, retrospective cohort standard practice, pediatric SCD patients aged 0 to 3 years
studies, reviews, and case reports, a significant reduction are given 125 mg penicillin V potassium twice daily. From
in the rate of vaso-occlusive crisis, longer time for onset 3 to 5 years of age, the dose is increased to 250 mg orally
of first and second crises, and a decrease in hospitalization twice daily. At 2 years or above, the 23-valent Streptococcus
were noted. However, there was no significant change pneumoniae polysaccharide vaccine (PPV-23) is also
to the patients’ requirement for transfusion, opioids, recommended. 110,111
or emergency room visits. Reported side effects are
constitutive, and the recommendation is an intravenous 6.2. Curative treatments
dose of 5 mg/kg over a period of 30 min at weeks 0, 2, and Although newborn screening, penicillin prophylaxis,
every 4 weeks thereafter. 94,105 and disease-modifying treatments discussed above have
lowered the rates of infant and pediatric mortality, and
6.1.7. Other potential candidates for treatment in SCD more than 94% of SCD children survive into adulthood,
Rivipansel is a pan-selectin inhibitor that was subjected to they are still affected by chronic complications, reduced
the initial phase of clinical trials without much promising quality of life as well as increased mortality risk in
results. However, the post hoc tests revealed that in patients adulthood. Hence, curing SCD has become the prime
who presented to hospitals within 26 h of onset of a vaso- goal for hemoglobinopathy teams. The only curative
occlusive episode, rivipansel shortened the length of treatment that was available till the FDA approval of gene
hospital stay and the duration of intravenous opioid use, therapy recently for SCD was hematopoietic stem cell
as well as significantly decreased the time of readiness-to- transplantation (HSCT). HSCT could be autologous where
discharge; therefore, it has been designated as an orphan a patient’s stem cells are genetically modified to correct the
drug by FDA. 105,106 point mutation, or can be allogeneic where defective stem
cells are replaced with healthy stem cells from the donor.
L-Arginine is a substrate for nitric oxide generation.
L-Arginine supplements decreased oxidative stress and Autologous HSCT was not found therapeutically effective
hemolysis in mice by increasing nitric oxide bioavailability. in SCD until the emergence of the recently approved
It also significantly reduced opioid use by >50% in SCD gene therapies for SCD. Allogeneic HSCT can involve
112,113
patients enrolled in a phase 2 trial. A Nigerian study myeloablative or non-myeloablative procedures. The
involving randomized controlled trials showed that more recent and promising curative therapies include the
arginine significantly decreased the time to resolution of FDA-approved gene therapies Casgevy and Lyfgenia, both
vaso-occlusive pain, the length of stay in hospital, and of which employ autologous transplantation of genetically
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the total use of analgesics. It was also shown to improve modified stem cells.
hemodynamics in pulmonary hypertension in SCD. Thus, 6.2.1. Allogeneic stem cell transplantation
arginine could be an inexpensive treatment for pain and
pulmonary hypertension in SCD. 105,107 Allogeneic HSCT is the only time-tested curative treatment
for SCD till date, but several limitations lie in how SCD
Phosphodiesterase 9 (PDE9) is an enzyme that patients can be eligible for the treatment.
degrades cGMP and is found in the neutrophils and RBCs
of patients with SCD. IMR-687, a selective PDE9 inhibitor, First, it involves a not-so-easy decision-making and
has been shown to increase levels of cGMP and fetal warrants a thorough discussion on benefits versus risks
hemoglobin F in vitro and is currently being investigated such as graft versus host disease, infections, organ injury,
for the treatment of SCD. 108,109 or unexpected effects on preexisting cardiopulmonary or
renal diseases.
6.1.8. Penicillin V potassium prophylaxis in children Second, HLA typing is necessary to identify a matching
Due to hyposplenism, the case fatality rate of pneumococcal donor. In fact, in 2014, the National Heart Lung and
infection in pediatric SCD patients <3 years of age is reported Blood Institute issued clear guidelines that more research
to be as high as 24%. As recommended by the American is needed on the selection procedures for patient–donor

Volume 4 Issue 1 (2025) 9 doi: 10.36922/gpd.4361