Primary immune deficiencies

Adenosine deaminase severe combined immunodeficiency (ADA-SCID)

Overview

ADA-SCID is a rare and life-threatening inherited disease of the immune system. Babies born with ADA-SCID have a faulty gene (the ADA gene).  Normally, this gene allows cells to build a protein called adenosine deaminase (ADA). When this protein is missing, the body cannot make a sufficient number of white blood cells (the cells in the blood that are responsible for fighting off infections). As a consequence, patients tend to have repeated and severe infections. If ADA-SCID is not treated properly, life expectancy can be very poor. ADA-SCID occurs in fewer than 1 in 200,000 births. 

Treating ADA-SCID

ADA-SCID can be treated in several ways. For example, patients can receive regular infusions of ADA protein. This requires weekly injections. Although this can help initially, over the long-term children remain at risk of life-threatening infections. Another way of treating ADA-SCID is by using a bone marrow or cord blood transplant when a suitable donor is available. This means that the patient with ADA-SCID receives stem cells, usually from the marrow of a healthy person. From these transplants stem cells, white blood cells can develop which will contain the functional ADA protein. If a matching donor is found, ideally a close family member, bone marrow or cord blood transplants can be very successful. However, when the donor is not a close enough match, there can be severe complications where the donor stem cells perceive the body of the patient as “foreign” and attack it.

Our approach

Doctors and scientists have invented a potential new way of treating ADA-SCID called "autologous ex vivo gene therapy". This involves making a copy of the normal gene in the laboratory and inserting it into a sample of the patient’s own blood or bone marrow stem cells, using a modified virus which carries the normal gene. This means that the stem cells now have a working copy of the missing gene (that is, the ADA gene). These genetically modified stem cells are then given back to the patient (the procedure is referred to as a “hematopoietic stem cell transplant”). After the stem cells are given back to the patient, they can grow and divide into new and functioning white cells that are able to fight off infections. One key advantage of “autologous ex vivo gene therapy” is that it uses the patient’s own cells (rather than a donor’s), so there is no chance that these cells attack the patient’s body or that the cells are rejected by the patient’s body.

Strimvelis®: EMA-approved autologous ex vivo gammaretroviral gene therapy

Strimvelis® is the first approved ex vivo gene therapy product, having received authorization by the European Medicines Agency in 2016. Strimvelis® is approved for the treatment of patients with ADA-SCID who do not have a suitably matched stem cell donor. The treatment is available at the Ospedale San Raffaele in Milan, Italy. For more information, please contact a healthcare professional.

Strimvelis® has not been approved by the FDA.

OTL-101: autologous ex vivo lentiviral gene therapy in clinical development for ADA-SCID

Orchard is developing OTL-101, autologous ex vivo lentiviral gene therapy for ADA-SCID. For more information, please contact a healthcare professional.

Wiskott-Aldrich syndrome (WAS)

Overview

Wiskott–Aldrich syndrome (WAS) is a rare and life-threatening inherited disease of the immune system. It occurs in approximately one baby in 200,000 births and affects boys almost exclusively. Babies born with WAS have a faulty gene that builds a protein called Wiskott–Aldrich protein (WASp). As a result, the number of platelets (the cells that are responsible for helping the body to form blood clots) is low and immune system cells (the cells in the blood that are responsible for fighting off infections) do not function normally. This means that patients with WAS are at risk of having bleeds, which can be very serious and life-threatening infections. In addition, some patients experience so called “autoimmune manifestations” (that is, the body attacks itself), severe eczema and cancers such as leukaemia or lymphoma.

Treating WAS

WAS can be treated in several ways. For example, doctors can attempt to prevent and manage symptoms of the disease with medicines to fight infections (such as antibiotics and immunoglobulin). This method is generally successful at preventing minor infections, but sometimes it is not able to combat severe infections. In addition, patients are given platelet infusions to prevent excessive bleeding. Another way of treating WAS is by using a bone marrow or cord blood transplant, when a suitable donor is available. This means that the patient with WAS receives stem cells from a healthy person. These normal stem cells will replace the defective ones and build a normal immune system and platelets to prevent infections and bleeds. If a matching donor is found, ideally a close family member, bone marrow or cord blood transplants can be very successful. However, when the donor is not a close enough match, there can be severe complications where the donor stem cells perceive the body of the patient as "foreign" and attack it.

Our approach

Doctors and scientists have invented a potential new way of treating WAS called "autologous ex vivo gene therapy". This involves making a copy of the normal gene in the laboratory and inserting it into a sample of the patient’s own blood or bone marrow stem cells, using a modified virus that carries the normal gene. This means that the stem cells now have a working copy of the missing gene (that is, the WAS gene). These genetically modified stem cells are then given back to the patient (the procedure is referred to as “hematopoietic stem cell transplant”). After the stem cells are given back to the patient, they can grow and divide into new and functioning white cells and platelets that are able to fight off infections and prevent bleeding. One of the features of "autologous ex vivo gene therapy" is that it uses the patient’s own cells (rather than a donor’s), so there is no chance that these cells attack the patient’s body or that the cells are rejected by the patient’s body.

OTL-103: autologous ex vivo lentiviral gene therapy for WAS

Orchard is developing OTL-103, autologous ex vivo lentiviral gene therapy for WAS. For more information, please contact a healthcare professional.

X-linked chronic granulomatous disease (X-CGD)

Overview

X-linked chronic granulomatous disease (or X-CGD) is a rare and life-threatening inherited disease of the immune system. It occurs in approximately one baby in 100,000 to 200,000 births and affects boys almost exclusively. Babies born with X-CGD have a faulty gene (the CYBB gene). As a result, the white blood cells (the cells in the blood that are responsible for fighting off infections) are unable to kill bacteria and fungi. This leads to repeated chronic infections, especially in the lung, and abscesses in organs such as the liver. It is estimated that around 40% of patients with X-CGD will die by 35 years of age (source: Van den Berg 2009).

Treating X-CGD

X-CGD is managed in several ways. For example, doctors can attempt to prevent and manage symptoms of the disease with medicines to fight infections (such as antibiotics antifungal medicines). This method is generally not successful in preventing severe infections. Another way of treating X-CGD is by using a bone marrow or cord blood transplant, when a suitable donor is available. This means that the patient with X-CGD receives white blood cells from a healthy person. These white blood cells are able to kill bacteria and fungi. If a matching donor is found, ideally a close family member, bone marrow or cord blood transplants can be very successful. However, when the donor is not a close enough match, there can be severe complications where the donor stem cells perceive the body of the patient as "foreign" and attack it.

Our approach

Doctors and scientists have invented a potential new way of treating X-CGD called "autologous ex vivo gene therapy". This involves making a copy of the normal gene in the laboratory and inserting it into a sample of the patient’s own blood or bone marrow stem cells, using a modified virus that carries the normal gene. This means that the stem cells now have a working copy of the missing gene CYBB gene. These genetically modified stem cells are then given back to the patient (the procedure is referred to as “hematopoietic stem cell transplant”). After the stem cells are given back to the patient, they can grow and divide into new and functioning white blood cells which can fight off infections. One of the features of "autologous ex vivo gene therapy" is that it uses the patient’s own cells (rather than a donor’s), so there is no chance that these cells attack the patient’s body or that the cells are rejected by the patient’s body.

OTL-102: autologous ex vivo lentiviral gene therapy for X-CGD

Orchard is developing OTL-103, autologous ex vivo lentiviral gene therapy for X-CGD. For more information, please contact a healthcare professional.