Gene Therapy Fully Reverses Friedreich’s Ataxia Changes in Mouse Model, Study Shows

Jose Marques Lopes PhD avatar

by Jose Marques Lopes PhD |

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LX2006 for Friedreich's ataxia

A gene therapy approach to deliver frataxin, the protein that’s deficient in Friedreich’s ataxia (FA) patients, was able to reverse disease-related changes in a new mouse model of the disease, a French study reports.

The study, “Rapid and Complete Reversal of Sensory Ataxia by Gene Therapy in a Novel Model of Friedreich Ataxia,” appeared in the journal Molecular Therapy.

Sensory ataxia, the lack of movement coordination due to loss of sensory input about body position, is an early event in FA. Neurological symptoms in this disease mainly result from degeneration of sensory neurons and their nerve fibers in the spinal cord and the cerebellum.

Possible therapies for FA may come from diverse approaches, including gene therapy. The authors previously showed that a gene therapy strategy using harmless viruses to deliver frataxin could prevent and reverse cardiomyopathy, or heart muscle disease, in a mouse model of FA. However, the question of whether sensory peripheral nerve damage (neuropathy) could be reversed remained unanswered.

In this study, scientists developed a new FA mouse model, which they considered better suited for testing gene therapy strategies for the primary sensory ataxia associated with this disorder.

This new model more specifically targets proprioceptive neurons, which are responsible for transmitting information about body position, movement, and balance. The mice were also engineered to enable conditional deletion of frataxin in cells expressing parvalbumin, a calcium-binding protein involved in various physiological processes, such as muscle contraction, and found in muscle, brain, and other types of tissue.

Researchers found that the new model mimics the sensory ataxia and nerve damage associated with FA, although with a more rapid and severe course. Mice exhibited a progressive loss of coordination and gait alterations.

They also observed that alterations in the central nervous system, including the cerebellum, occurred after disease onset in the periphery. Neurons lacking frataxin, although dysfunctional, could survive for many weeks, the scientists reported.

They then delivered viral vectors (carriers) containing frataxin into the vein, which completely prevented the start of peripheral sensory nerve damage. Combined intravenous and brain delivery of these vectors after the onset of behavioral impairment reversed behavioral, physiological, and cellular changes within a week.

“Our results strongly demonstrate that frataxin-deficient proprioceptive neurons with severe phenotype survive for several weeks and can be rapidly and completely rescued by gene therapy in the mouse model,” the researchers wrote. “Thus, this study establishes the pre-clinical proof of concept for the potential of gene therapy in treating FA sensory neuropathy.”

Comments

Bernhard Hunziker avatar

Bernhard Hunziker

This news is really exciting and brings hope to everyone suffering from this disorder. Hope is a very powerful Thing. Thank you and keep up your good work!

Navin avatar

Navin

Excellent....cheers and congrats researchers team

DUCROS avatar

DUCROS

MERCI.

renato avatar

renato

Is there a way to contact these researchers, because im suffering.

PLease reply [email protected]

Vicki kuchowicz avatar

Vicki kuchowicz

My niece is suffering also. She is 43, divorced and has two little ones. Her speech is pretty bad and uses a cane that barely helps. If you find anything out olease let me know. If I can find anything out I will let you know. Thanks.
[email protected]

graciela avatar

graciela

I am from Argentina, I have two relatives suffering from this illness. Please, I need to contact the researchers. Thanks.
[email protected]

Melissa Evans avatar

Melissa Evans

Who can I contact a 57 living with this disease since I was 18 years old I am still in good condition. Who do I contact

R R Rao avatar

R R Rao

My Daughter of 21 yrs is suffering from Friedreichs Ataxia for the last 11 yrs. Is there any chance for cure.?? please intimate if any to 9394166566.(Andhra Pradesh - India)
[email protected]

ali candan avatar

ali candan

I am from Turkiye, I have a nephew suffering from this illness. Please, I need to contact the researchers. Thanks.
[email protected]

Alton avatar

Alton

My dad's friend's dauter has that and I relley hope they find a cure

Martin N. avatar

Martin N.

Thank you for researching and congrats to this success! If the therapy is ready for humans please let me know. Greetings from Germany =)
[email protected]

Anie avatar

Anie

I'm currently do some gene editing in class that can cut out pieces of the GAA sequence in the gene. Which is the mutation that cause FA. Wish us luck

Jamie avatar

Jamie

Are y’all using the Cas9 gene edit tool? How’s it working out?

julius baca avatar

julius baca

I have a mom and brother suffering from this disease if you could contact me please call 304 952 9525 or via email [email protected]

wil.wollersheim avatar

wil.wollersheim

My daughter is suffering of FDA and I hope that he problem will be solved on X25gen chromosome 9, so that the repeat expansion of GAA isn't possible anymore and the production of Frataxin will be continued. That would be the dream of all patients.
Good Job All our hope is on you.
greetings from Holland.([email protected])

Joanne Villarreal avatar

Joanne Villarreal

My daughter suffers from FA and I was wondering where we are today with this research? Are we getting any closer to developing a way to eradicate this horrible disease? Are there any treatments developed at this time?

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