SICKLE CELL DISEASE

Sickle cell anemia (SCA) is an inherited hematological disorder caused by a single point mutation in the HbB gene, which encodes the beta subunit of hemoglobin. This mutation results in the production of an aberrant hemoglobin variant that induces erythrocytes to adopt a characteristic sickled morphology. These deformed cells exhibit increased adhesiveness within the vasculature, impeding blood flow and leading to ischemic organ damage, severe pain episodes, and potentially severe complications such as vision loss, stroke, or mortality. Additionally, SCA is associated with anemia, dyspnea, chronic pain, jaundice, and recurrent infections, cumulatively leading to reduced life expectancy. It is estimated that approximately 500,000 children are born with SCA annually, with India contributing to about 50% of these cases.

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The burden of Sickle Cell Disease (SCD) in India is notably high, particularly among tribal populations in Kerala, Tamil Nadu, Madhya Pradesh, Maharashtra, Gujarat, Chhattisgarh, and Odisha, rendering India the second most affected country globally. The prevalence is exacerbated within communities of lower socioeconomic status, highlighting a significant public health challenge. 

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Current SCD management primarily involves symptomatic treatment, including hydroxyurea administration, blood transfusions, and hematopoietic stem cell transplantation, as no definitive cure is presently available. Recent initiatives by governmental and non-governmental organizations have focused on genetic counseling, systematic screening, and patient monitoring in high-prevalence regions.

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Advancements in CRISPR-Cas-based gene editing therapies offer promising avenues for a permanent cure. The RNA Biology Lab at CSIR-IGIB is actively developing CRISPR-Cas9-based ex vivo therapeutics for SCD, supported by the Ministry of Tribal Affairs (MoTA) and the Department of Science and Technology (DST). In collaboration with clinical and research partners, including AIIMS New Delhi, SCIC Raipur, CSIR-IICT, ICMR-NIIH Mumbai, NNF Bangalore, and the University of Washington Seattle, the lab is pioneering robust, cost-effective gene editing strategies to address the growing SCD burden in India.

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PRELEVANCE

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The prevalence of Sickle Cell Disease (SCD) in India varies significantly, ranging from 1% to 40% across different regions. Madhya Pradesh, home to major tribal groups such as the Gonds and Bhils, bears the highest disease burden, with more than half of its districts classified as high-prevalence zones. In Maharashtra, SCD prevalence ranges from 0% to 35%, predominantly among the eastern tribal communities, including the Pardhans, Otkars, Madhias, and Bhils. However, comprehensive epidemiological data remains scarce for several states, particularly Uttar Pradesh, Uttarakhand, Bihar, and the entire northeastern region.

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SCREENING APPROACHES

Most SCD screening programs in India utilize the Sickling Test or the Rapid Solubility Test, followed by confirmatory hemoglobin electrophoresis. The dithionate qualitative solubility test, developed indigenously, is widely employed due to its cost-effectiveness, simplicity, and high sensitivity and specificity at room temperature, making it a reliable first-line screening tool. The test relies on the turbidity resulting from differential lysis of soluble HbA versus insoluble HbS, enabling efficient point-of-care assessment.

In recent years, High-Performance Liquid Chromatography (HPLC) has gained popularity for the accurate identification of sickle cell carriers and affected individuals. Additionally, some centers have adopted capillary electrophoresis for enhanced diagnostic precision.

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CURRENT TREATMENT MODALITIES

Although no definitive cure for SCD is currently available in Indian clinical settings, several therapeutic strategies help manage symptoms and improve patient quality of life:

Hydroxyurea Therapy: Administered at 10-15 mg/kg/day, hydroxyurea promotes the production of fetal hemoglobin, thereby reducing the proportion of sickled cells. It also decreases leukocyte counts, mitigating vaso-occlusion and reducing the frequency of vaso-occlusive crises and blood transfusion requirements.

Blood Transfusion Therapy: Acute transfusions are employed to correct severe anemia, while chronic transfusion regimens are used to prevent primary strokes or recurrent episodes. Chronic transfusions also reduce the risk of acute chest syndrome, particularly when hydroxyurea is ineffective.

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SUPPORTIVE AND PREVENTIVE MEASURES

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• Prophylactic Penicillin: Administered from birth until five years of age to prevent severe infections.

• Pain Management: Acute pain crises are managed with opioid analgesics, while chronic pain is controlled using non-opioid painkillers.

• Vaccinations and Supplements: Patients older than two years are recommended to receive pneumococcal vaccines and folic acid supplementation to support erythropoiesis.

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Severe SCD is typically characterized by three or more pain crises requiring hospitalization or three or more blood transfusions within a year, warranting more aggressive management strategies.
Despite significant advancements in gene therapy worldwide, no permanent curative gene therapy for SCD is currently available in Indian clinical settings. Ongoing research and clinical trials in CRISPR-Cas9 gene editing are showing promise for potential curative interventions. Meanwhile, comprehensive symptom management and preventive strategies continue to play a crucial role in improving patient outcomes and quality of life.​​​​​​​​​