While gene therapy offers the promise of addressing and treating many genetic disorders, creating a better quality of life for many people, there are also ethical issues associated with this therapy. For example, some people question the ethics of gene therapy if we do not know how it might affect or impact someone. Admittedly, there are many situations in which gene therapy has shown immense promise and benefit. But in the case of Strimvelis, a gene therapy from Orchard Therapeutics, there are now serious concerns about its efficacy and safety. According to Fierce Pharma, Strimvelis was linked to leukemia in a patient with ADA-SCID who previously received the treatment.
In 2016, Strimvelis was approved in the European Union for the treatment of ADA-SCID (adenosine deaminase deficiency/severe combined immunodeficiency). Initially, the therapy was developed by GlaxoSmithKline. Strimvelis edits hematopoietic stem cells (HTSCs) from the patient to add a functional ADA gene. Usually, in patients with ADA-SCID, this gene is mutated. Once the stem cells are placed back into the body, the patient is able to produce an adequate amount of ADA.
During a Compassionate Use Program, the patient in question was treated. Only 16 patients ever have received Strimvelis. At this time, no other patients will be treated until Orchard Therapeutics is able to further research the connection between Strimvelis and leukemia.
In a press release, Orchard Therapeutics shared:
Preliminary findings suggest this diagnosis [of lymphoid T-cell leukemia] may be attributable to an insertional event related to treatment with Strimvelis. Leukemia arising from the insertion of gammaretroviral vectors into the genome, a process known as insertional oncogenesis (or mutagenesis), is a known risk factor for gammaretroviral vector-based gene therapy and is described in the Strimvelis product information as a potential risk of treatment.
Adenosine Deaminase Deficiency (ADA)
An ADA gene defect prevents the body from creating enough adenosine deaminase. Normally, this enzyme helps break down and remove deoxyadenosine from the body. But when the body does not produce enough adenosine deaminase, it is unable to clear this cellular by-product. As a result, deoxyadenosine accumulates, causing lymphocyte damage. Then, as lymphocytes become damaged, the body is unable to protect against infection. Patients must receive a defective gene from both parents to inherit this condition.
ADA deficiency impacts anywhere from 1 in every 200,000 to 1 in every million births. Symptoms usually appear in infancy and prevent infants from fighting infections. Symptoms from ADA deficiency, and SCID, include:
- Frequent skin rashes
- Absent tonsils and lymph nodes
- Developmental delays
- Failure to thrive
- Chronic diarrhea
- Lung damage
Severe Combined Immunodeficiency (SCID)
A variety of gene mutations are linked to severe combined immunodeficiency (SCID), a group of conditions that impact immune cell development and function. When these gene mutations affect T- and B-cells, the immune system has a more difficult time fighting infections. Some forms of SCID are inherited in an autosomal recessive pattern; others are X-linked. Symptom onset appears in infancy. Generally, SCID affects those of Navajo, Apache, or Turkish heritage more often than other groups. Symptoms include the following infections, which rarely respond to treatment:
- Frequent ear infections
- Yeast infections
- Skin infections
- Blood infections