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Rare Diseases And Foundations: Gene Therapy Developments #3

May 24, 2013

This is a third in a series of Blog Posts this week, on the topic of gene therapy developments in the rare disease and orphan drug space. This blog post discusses two rare disease patient families, their journeys to set up foundations, and their success in leading the way for funding gene therapy research.

I – Giant Axonal Neuropathy (GAN) And Hannah’s Hope Fund

Giant Axonal Neuropathy (GAN) is an ultra rare disease, with only about fifty cases worldwide. Several years ago, Hannah Sames is diagnosed with GAN. GAN is a recessively inherited condition that results in progressive nerve death, with patients typically becoming quadriplegic. The disease is caused by a dysfunction of a gene called gigaxonin. Without gigaxonin in nerve cells, proteins can’t be broken down and accumulate, resulting in swollen axons.

Hannah’s Hope Fund (HHF), a 501(c)(3) public charity, is created by Hannah’s parents, Matt and Lori Sames, for the purpose of raising “funds to support the development of a treatment and cure for GAN, and to be the resource for doctors, scientists and families worldwide.” HHF has raised as of April 30, 2013, over $1 million to help fund the start of a gene therapy clinical trial.  At the next Recombinant DNA Advisory Committee meeting at the NIH, scheduled for June 11-12, 2013, a Phase I clinical trial to evaluate gene therapy for GAN is to be reviewed. It will be the first gene therapy delivered to the spinal cord. This is just one example of rare disease patient families setting up not-for-profits and leading the way for funding research. A research article in the current issue of The Journal of Clinical Investigation looks at GAN. Here is the citation :

J Clin Invest. Giant axonal neuropathy–associated gigaxonin mutations impair intermediate filament protein degradation. 2013;123(5):1964–1975. doi:10.1172/JCI66387.

A book, The Forever Fix: Gene Therapy And The Boy Who Saved It, by Ricki Lewis, explores gene therapy and its science, and its impact on children and their families. One story in the book follows Hannah and her family’s journey with GAN.

II – Canavan Disease And The Canavan Research Foundation

Canavan Disease is a rare genetic disorder resulting in severe neurological dysfunction and eventually results in the degeneration of the brain. Patients with Canavan Disease gradually lose the ability to swallow food, to see, and usually die within the first decade of life.

The Canavan Research Foundation is founded by Drs. Helene and Roger Karlin, whose daughter Lindsay is diagnosed with Canavan Disease. The couple met with Dr. Paola Leone and Dr. Matthew During at Yale University, and they work on developing a gene therapy approach for the disease. After a year and a half, a vector system to transport new genes into brain cells is developed. The new genes are administered into the ventricles (area between the brain where spinal fluid flows) of Lindsay and another child with the same disease. This gene therapy, administered in New Zealand in 1996, is the world’s first gene therapy for a genetic brain disease. Both children showed improvement.

The same gene therapy is approved by the FDA in 1998 to be used in a second experimental trial in the US. Due to both the US regulatory red tape  and the death in 1999, of 18-year-old Jesse Gelsinger after an experimental gene therapy for a metabolic disease, it wasn’t until 2001 that the Canavan trial begins. The surgeons inject the gene therapy (a virus called AAV2 carrying a healthy ASPA gene) into six holes in a patient’s brain. All of the children are still alive today, but “the 3 oldest children, including Lindsay, are just as disabled as they were before the procedure. The rest showed some minor improvements … but because the disease is so rare and so variable, it’s hard to know whether the gains were due to gene therapy, better medical care …”. The Karlins and their foundation have now shifted focus to stem cell research.

Please Note: “ExRNA Cartoon” National Institute of Health [Public domain] | Wikimedia Commons.

Copyright © 2012-2013, Orphan Druganaut Blog. All rights reserved.

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