Man’s joint damage eased by gene therapy, robotic hip replacement
27-year-old with hemophilia A was in clinical trial
Combining gene therapy with minimally invasive, robot-assisted hip replacement surgery safely and effectively treated severe joint damage for a 27-year-old man in China with hemophilia A, according to a case report.
The approach significantly reduced the need for replacement therapy to counter deficient blood-clotting factor VIII (FVIII) and enabled the successful reconstruction of the hip joint, resulting in functional recovery.
“This case report may represent a novel precision treatment strategy,” the researchers wrote. The man’s experience “suggests potential safety and feasibility, with a dramatic 96% reduction in exogenous FVIII requirements,” they said.
The case report, “Robot-assisted total hip arthroplasty following gene therapy for hemophilia a arthropathy: a case report,” was published in Arthroplasty.
Hemophilia A is caused by mutations in the F8 gene that cause deficient or defective FVIII production, leading to reduced levels or complete absence of the protein. A hallmark sign of hemophilia is bleeding into the joints, which can lead to joint swelling, stiffness, and pain, impairing patients’ mobility.
Man was in trial evaluating gene therapy
Although gene therapies have recently been approved to treat hemophilia, their efficacy has not been assessed in the context of joint surgeries with high potential for bleeding.
The man whose case was described in the report was treated with an experimental gene therapy in a clinical trial (NCT04728841) and underwent robot-assisted total hip arthroplasty (THA), or hip replacement, for severe hemophilia-associated hip damage.
The trial is evaluating the safety and tolerability of Gritgen Therapeutics’ GS1191-0445 gene therapy, which uses a modified and harmless adeno-associated virus, called AAV8, to deliver a shorter version of the F8 gene to cells in the liver.
Although the gene therapy successfully increased FVIII activity, the man required total hip arthroplasty about one year later due to severe joint damage that caused him debilitating pain and restricted his mobility. Imaging scans revealed severe deformities in the head of the left femur, the uppermost part of the thigh bone (femur) that fits into the hip socket, forming the hip joint.
Surgeons used a minimally invasive, muscle-sparing approach to remove the damaged femur’s head and a robotic system to guide them through the procedure. They replaced the removed bone with a prosthetic implant.
The procedure also involved removing the synovial membrane, or joint lining, and reconstructing the joint structures. Imaging scans 24 hours after the surgery demonstrated a successful restoration of the hip joint, with near-equal leg length.
No FVIII replacement therapy, which involves supplying a working version of FVIII, was needed before or during the surgery, and the total blood loss was 300 mL.
The day after the surgery, a drainage volume of 150 mL, combined with a drop in hemoglobin (the protein that carries oxygen in red blood cells), prompted the transfusion of plasma (the liquid part of blood that contains clotting factors), red blood cells, and a minimal amount of FVIII replacement therapy. Drainage volume is a measurement of the fluid collected in the reservoir of a surgical drain, ensuring that fluids do not collect inside the body where they could cause pressure or complications.
With the assistance of a physical therapist, the man was able to sit, stand, and attempt walking with a walker on the day after the surgery. A day later, he was able to perform normal walking exercises with the aid of a walker. He did not report any discomfort, and no further complications were observed.
The man maintained normal blood coagulation and achieved favorable wound healing and functional recovery.
“This case confirms the potential of combining gene therapy and [robotic assisted]-THA to manage advanced hemophilic arthropathy, effectively minimizing the need for exogenous clotting factor,“ the researchers wrote.
It also suggests that “broader adoption of gene therapy may enable early intervention to prevent joint deterioration in hemophilia patients, ultimately reducing the need for arthroplasty,” they wrote.
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