Perissa
Well-Known Member
My horse has just started this treatment. Does anyone know another horse that has had this treatment and what was the outcome please?
My horse does not have DJD but has had major surgery to remove a cystic bone lesion from his shoulder joint. My vet at Liphook Equine Hospital describes it as 'a new and very exciting new treatment'.
A bit about IRAP
Degenerative joint disease is a common cause of lameness in horses. Injury to a joint initiates a vicious cycle of inflammation leading to degenerative changes within the joint including loss of the articular cartilage. The aim of treatment is to protect the cartilage from furtherdamage and break the cycle of inflammation to prevent further deterioration.
Current therapy consists of anti-inflammatory and / or chondroprotective drugs, which may be administered directly into the affected joint or be given to the horse by injection or in food. Repeated treatments may be necessary.
An alternative approach which shows great promise is gene therapy. Instead of having a therapeutic substance injected into the joint, the patient is treated with a gene which will stimulate the production of the required substance in situ. This is achieved by using a vector, such as a virus, to carry the gene into the nucleus of the target cell.
Gene therapy has been shown to be successful in treating equine joint disease in a collaborative study involving the Departments of Orthopaedic Surgery and Molecular Genetics at the University of Pittsburgh School of Medicine, and the Orthopaedic Research Laboratory at Colorado State University.
They chose to investigate interleukin-1 receptor antagonist (IL-1 Ra) from among several genes which have potential benefit for treatment of degenerative joint disease. Interleukin-1 ( IL-1) is an inflammatory mediator. It activates metalloproteinase enzymes and causes the production of PGE - which further promotes inflammation. Interleukin-1 receptor antagonist inhibits IL-1 and so acts to reduce inflammation.
The first step was completed in 1998 with the identification of the gene responsible for the production of interleukin-1 receptor antagonist in the horse (Eq-IL-1 Ra). The researchers then developed a way of transferring the gene into the nucleus of the synoviocytes (the main type of cell forming the lining of the joint).
For the vector they used an adeno virus. They removed some of its own genetic material and replaced it with the EQ-IL-IRa gene. They were then able to infect synoviocytes growing in tissue culture with the adenovirus vector carrying the EQ-IL-IRa gene.
The synoviocytes produced increased amounts of the IL-1 Ra protein within 48 hours of treatment- indicating that the genetic material had been successfully transferred. Further investigations followed in which the research team determined the optimum dose of Eq IL-IRa vector required to produce the maximum amount of IL-IRa protein in normal equine joints.
Six normal horses, between 2 and 5 years old, were used. The researchers injected one mid-carpal (knee) joint and one metacarpophalangeal (fetlock) joint of each horse with virus particles containing the Eq IL-IRa gene. The other leg was not treated so it could act as a control. A different amount of virus particles was used in each horse to identify the most appropriate dose. They found that the IL-IRa production lasted for 28 days after treating with 10 x 1010 and 20 x l010 adenovirus particles carrying the IL-IRa gene. This is longer than has been achieved by previous investigators and may be due to the fact that the IL-Ra gene used this time was of equine origin.
Sixteen horses were involved in the final stage of the investigation. All had experimental osteo-arthritis in one inter-carpal (knee) joint. Half of the horses received treatment with Ad Eq IL-IRa into the arthritic joint, the other eight horses received no treatment. Fifty-six days after treatment the researchers noted a significant improvement in lameness and pain in the reated horses. There was also a reduction in joint swelling in treated horses.
"Based on the significant improvements in joints with osteoarthritis tre ated with the Ad Eq IL-IRa gene, this therapy is practical and efficient for horses with osteoarthritis " says Dr David Frisbie, spokesman for the group. "Gene transfer of interleukin-1 receptor antagonist is an attractive treatment modality for the equine patient with osteo-arthritis."
Dr Frisbie adds that the same experimental model of osteoarthritis has been used to assess the benefit of other, currently used medications. Compared with such treatments as corticosteroids or hyaluronate injected into the joint, gene therapy was more effective at reducing the progression of experimentally induced equine arthritis. He points out that further work needs to be done to confirm ) that similar improvement is seen in clinical cases of arthritis. If so, it is likely that gene therapy will revolutionise the treatment of equine arthritis in the near future.
My horse does not have DJD but has had major surgery to remove a cystic bone lesion from his shoulder joint. My vet at Liphook Equine Hospital describes it as 'a new and very exciting new treatment'.
A bit about IRAP
Degenerative joint disease is a common cause of lameness in horses. Injury to a joint initiates a vicious cycle of inflammation leading to degenerative changes within the joint including loss of the articular cartilage. The aim of treatment is to protect the cartilage from furtherdamage and break the cycle of inflammation to prevent further deterioration.
Current therapy consists of anti-inflammatory and / or chondroprotective drugs, which may be administered directly into the affected joint or be given to the horse by injection or in food. Repeated treatments may be necessary.
An alternative approach which shows great promise is gene therapy. Instead of having a therapeutic substance injected into the joint, the patient is treated with a gene which will stimulate the production of the required substance in situ. This is achieved by using a vector, such as a virus, to carry the gene into the nucleus of the target cell.
Gene therapy has been shown to be successful in treating equine joint disease in a collaborative study involving the Departments of Orthopaedic Surgery and Molecular Genetics at the University of Pittsburgh School of Medicine, and the Orthopaedic Research Laboratory at Colorado State University.
They chose to investigate interleukin-1 receptor antagonist (IL-1 Ra) from among several genes which have potential benefit for treatment of degenerative joint disease. Interleukin-1 ( IL-1) is an inflammatory mediator. It activates metalloproteinase enzymes and causes the production of PGE - which further promotes inflammation. Interleukin-1 receptor antagonist inhibits IL-1 and so acts to reduce inflammation.
The first step was completed in 1998 with the identification of the gene responsible for the production of interleukin-1 receptor antagonist in the horse (Eq-IL-1 Ra). The researchers then developed a way of transferring the gene into the nucleus of the synoviocytes (the main type of cell forming the lining of the joint).
For the vector they used an adeno virus. They removed some of its own genetic material and replaced it with the EQ-IL-IRa gene. They were then able to infect synoviocytes growing in tissue culture with the adenovirus vector carrying the EQ-IL-IRa gene.
The synoviocytes produced increased amounts of the IL-1 Ra protein within 48 hours of treatment- indicating that the genetic material had been successfully transferred. Further investigations followed in which the research team determined the optimum dose of Eq IL-IRa vector required to produce the maximum amount of IL-IRa protein in normal equine joints.
Six normal horses, between 2 and 5 years old, were used. The researchers injected one mid-carpal (knee) joint and one metacarpophalangeal (fetlock) joint of each horse with virus particles containing the Eq IL-IRa gene. The other leg was not treated so it could act as a control. A different amount of virus particles was used in each horse to identify the most appropriate dose. They found that the IL-IRa production lasted for 28 days after treating with 10 x 1010 and 20 x l010 adenovirus particles carrying the IL-IRa gene. This is longer than has been achieved by previous investigators and may be due to the fact that the IL-Ra gene used this time was of equine origin.
Sixteen horses were involved in the final stage of the investigation. All had experimental osteo-arthritis in one inter-carpal (knee) joint. Half of the horses received treatment with Ad Eq IL-IRa into the arthritic joint, the other eight horses received no treatment. Fifty-six days after treatment the researchers noted a significant improvement in lameness and pain in the reated horses. There was also a reduction in joint swelling in treated horses.
"Based on the significant improvements in joints with osteoarthritis tre ated with the Ad Eq IL-IRa gene, this therapy is practical and efficient for horses with osteoarthritis " says Dr David Frisbie, spokesman for the group. "Gene transfer of interleukin-1 receptor antagonist is an attractive treatment modality for the equine patient with osteo-arthritis."
Dr Frisbie adds that the same experimental model of osteoarthritis has been used to assess the benefit of other, currently used medications. Compared with such treatments as corticosteroids or hyaluronate injected into the joint, gene therapy was more effective at reducing the progression of experimentally induced equine arthritis. He points out that further work needs to be done to confirm ) that similar improvement is seen in clinical cases of arthritis. If so, it is likely that gene therapy will revolutionise the treatment of equine arthritis in the near future.
