NEJM: LentiGlobin Gene Therapy for Sickle Cell Disease

Sickle cell disease is an inherited disorder of the function of hemoglobin molecules.
When the hemoglobin molecules are exposed to various environments, the red blood cell hemoglobin polymerizes and distorts into a sickle shape
.

Sickle cell disease is characterized by recurrent blood vessel blockages that cause painful crises

Vascular children

Gene therapy for sickle cell disease with LentiGlobin includes autologous transplantation of hematopoietic stem and progenitor cells, transduction of a BB305 lentiviral vector encoding a modified β-globin gene (encoding anti-sickle hemoglobin HbA ^T87Q )
.

HbA ^{T87Q T87Q}

In an ongoing Phase 1-2 trial, investigators optimized the treatment process for the initial 7 patients with sickle cell disease in arm A and 2 patients in arm
B.

Cohort C was established for the pivotal assessment of LentiGlobin in sickle cell disease with stricter inclusion criteria requiring at least 4 serious vascular occlusive events in the 24 months prior to enrollment

Changes in hemoglobin levels

Changes in hemoglobin levels

As of February 2021, all 35 patients received an infusion of LentiGlobin, with a median follow-up of 17.
3 months (range 3.
7-37.
6 months)
.

Implantation occurred in all 35 patients

Median total hemoglobin levels increased from 8.

Serious Vascular Occlusion Events with LentiGlobin Infusion

Serious Vascular Occlusion Events with LentiGlobin Infusion

The hemolytic index of the tested patients was generally decreased
.

Of the 25 evaluable patients, all had resolution of serious vaso-occlusive events, with an average of 3.

The overall decrease in the hemolytic index of the test patients

In conclusion, a one-time treatment with LentiGlobin resulted in sustained production of HbA ^T87Q from most red blood cells , thereby reducing hemolysis and completely resolving severe vascular occlusion events

One-time treatment with LentiGlobin resulted in sustained production of HbA T87Q by most red blood cells , ^{resulting in} reduced hemolysis and complete resolution of severe vascular occlusive events of vascular occlusive events ^T87Q

Original source:

Original source:

Julie Kanter, et al.