Gene Therapy

Alport syndrome is an inherited disorder characterized by progressive kidney disease, hearing loss, and eye abnormalities. It is caused by a mutation in one of the genes encoding for part of type 4 collagen, an important structural protein.

No cure currently exists for Alport patients, but research is ongoing into new and potential therapies. Gene therapy is an avenue that has been dormant for a while, but interest and efforts here are picking up again.

What is gene therapy?

Gene therapy is a treatment approach that introduces new genetic material into cells with the aim of replacing or fixing a disease-causing mutation.

For example, where a disease is caused by a lack of a specific protein, gene therapy could be used to introduce a functioning copy of the mutated gene into the patient’s cells. If this copy works, the patient’s own cells could produce a working copy of the required protein, which may slow or reverse disease symptoms.

With new gene editing techniques, it may even be possible to fix an existing mutated gene. One such experimental technique is the CRISPR/Cas9 system. This tool — still in early investigational stages — might one day enable the removal of a faulty section of a gene by providing a guide sequence to target that part of the genome. Using a template for the healthy gene segment provided alongside the CRISPR/Cas9 tool and the body’s own DNA repair system, the faulty portion could be corrected.

History of gene therapy in Alport syndrome

Potentially, Alport syndrome might be treated with gene therapy as it is caused by a mutation in one of three genes: COL4A3, COL4A4, or COL4A5. Gene therapy could allow the body to produce the missing type 4 collagen protein, addressing symptoms that affect the kidneys, eyes, and ears. The idea of gene therapy for Alport syndrome has been explored since the 1990s, but progress has been limited and it remains in early testing.

For example, a study at Washington University School of Medicine, led by  Jeffery Miner, used gene therapy to provide a functioning type 4 collagen-encoding gene to mice in a model of Alport syndrome.  Study results found the therapy significantly extended the animals’ lifespan and slowed the progression of kidney disease, and were published in the Journal of the American Society of Nephrology in November 2013.

Future of gene therapy in Alport syndrome

More recently, a preclinical study of gene therapy in Alport syndrome was chosen to be part of the 2018 ASF Research Program. This study is being jointly led by Alessandra Renieri at the University of Siena in Italy and Mary Nabity at Texas A&M University.

A proof-of-concept study, it uses a dog model of the disease to test whether gene therapy can correct a mutation in the COL4A5 gene.

Researchers are using the CRISPR/Cas9 system to target the faulty COL4A5 gene in a kidney cell taken from urine. The gene with the edited DNA will then be delivered back to the animals using an adeno-associated virus or AAV, which is a harmless virus modified to contain the gene of interest, in this case, the “fixed” portion of the COL4A5 gene. The goal is to see if the engineered gene-carrying virus “infects” the kidneys, and the corrected gene survives.

The CRISPR/Cas9 system is being investigated in a number of diseases, including research looking into its therapeutic potential in kidney disease.

Although still in its infancy, gene therapy may one day be part of clinical trials assessing its potential in Alport syndrome patients.


Alport Syndrome News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.