Duchenne Muscular Dystrophy Patient Dies in Gene Therapy Trial

 

Fierce Biotech recently carried an article about the death of Terry Horgan. Terry was a 27-year-old Duchenne muscular dystrophy (DMD) patient and the brother of the CEO of the clinical trial sponsor. The study involved CRISPR, a now well-known gene editing tool.

Duchenne is caused by a mutation in a gene that produces a protein called dystrophin. The goal of the trial was to produce the muscle protein (dystrophin) that his body was not producing hoping to stabilize symptom progression.

Terry was the only participant in the trial (NCT05514249) that was designed for him. He died eight days after receiving the therapy. Most Duchenne patients eventually die from heart or lung issues.

The developer, Sarepta Therapeutics, had previously restricted the therapy to children ages four through eight.

An investigation of Terry’s death had begun in order to determine if it was in any way connected to CRISPR transactivation. A post-mortem analysis showed severe respiratory distress.

The trial sponsor, Cure Rare Disease, reported the findings as being injuries to the patient’s lungs possibly caused by the dose of treatment he received.

Vectors transport genetic material into cells and are harmless when stripped of disease-causing genes.

Further, the findings showed immune signaling together with a capillary leak causing toxicity in cases of advanced DMD treated with high-dose rAAV gene therapy.

Later it was learned that Terry’s immune system had an overreaction to the virus that was used to deliver the treatment. Recent studies are using another type of virus considered to be safer for that purpose. There are some observers who are skeptical about the ethics surrounding a clinical trial involving only one person. They believe that a trial must have at a minimum 5, 10, or 20 participants so they can have data to analyze.

Terry once wrote that as he realized the devastation caused by DMD, he began to develop deep fears. He said that there were no prospects for clinical trials for his disease but then he became aware of the possibility of a customized drug and was enrolled in the study on August 31.

The treatment began with his immune system being suppressed followed by a one-time treatment of gene editing which was monitored by the hospital staff at Massachusetts University medical school.

A CRISPR expert at the UC Berkeley Genomics Institute, Fyodor Urnov, said that no other trial has targeted DMD with this form of virus delivering a modified type of CRISPR.

He added that some gene trials treating blood diseases such as sickle cell disease involve the removal of stem cells from a patient’s blood via CRISPR and returning the altered cells back into the patient.

Therefore, Dr. Urnov does not think that Terry’s death will impact gene therapy related to blood diseases. However, he said that finding the cause of his death will still be helpful to scientists in general.

 

 

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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