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Therapeutic Strategies

Conventional strategies to treat Friedreich's ataxia are designed to ease symptoms caused by cellular events that are downstream of the loss of frataxin function and have not shown clinical benefit. Researchers at the Li Weibo Institute for Rare Diseases Research seek to identify new, effective therapeutic targets that address the root cause of the disease – reduced FXN expression.  Restoring expression of the FXN gene, and consequently, restoring frataxin function, is a potential therapeutic approach for the disease. Researchers at the Institute are taking two approaches to restoring FXN expression, both of which involve studies in cell lines derived from patients.


Specifically, the lab of Dr. Watts is exploring the potential of oligonucleotides (short stretches of chemically modified DNA) to activate frataxin expression — and Drs. Green and Fang are collaborating to identify therapeutic small molecule inhibitors that can reactivate FXN expression — in cell lines derived from patients with Friedreich’s ataxia and in mouse models of the disease. Ultimately, these strategies aim to elevate frataxin levels, thereby lessening the consequences of frataxin deficiency and potentially alleviating disease symptoms.   

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Activation of frataxin protein expression by antisense oligonucleotides targeting the mutant expanded repeat

Authors: Li L, Shen X, Liu Z, Norrbom M, Prakash TP, O'Reilly D, Sharma VK, Damha MJ, Watts JK, Rigo F, and Corey DR


Published in 2018 in Nucleic Acid Therapeutics


This study explored FXNgene activation by antisense oligonucleotides (ASOs) and duplex RNAs (dsRNAs) in varied cell lines derived from patients with Friedreich’s ataxia. The results showed successful gene activation occurred using a chemically diverse collection of ASOs and dsRNAs,laying a broad foundation for future drug development.

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Friedreich’s Ataxia Investigators

Michael Green

Michael Green, MD, PhD

Chair and professor of molecular, cell & cancer biology, Lambi and Sarah Adams Chair of Genetic Research, Co-director of the Li Weibo Rare Diseases Research Institute, Vice Provost for Strategic Research Initiatives

Green Lab

Jonathan Watts, PhD

Associate professor, RNA Therapeutics Institute

Watts Lab

Minggang Fang, PhD

Minggang Fang, PhD

Assistant professor of molecular, cell and cancer biology

Website

Clinical Trials

At the Li Weibo Institute for Rare Diseases Research, our researchers and clinicians are dedicated to finding new treatment options for patients. Our clinical trials program is another way we continue to advance treatments and make new discoveries. If you or someone you know may be interested in a clinical trial, please subscribe for updates and you will be notified when we open up a new trial.

 

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Several years ago, we began investigating the mechanism by which genes are turned off on the X chromosome — a process termed X chromosome inactivation (XCI). In females, XCI is a naturally occurring phenomenon in which one of the X chromosomes is randomly turned off, or silenced, as a way to equalize the dosage of the X chromosome between females (who have two X chromosomes) and males (who have one).

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The research in my laboratory is focused on improving genome editing technologies so that they can be applied to the development of therapeutics. Inspired by the opportunity to improve the lives of patients with debilitating disorders, my lifelong goal as a scientist is to translate genome editing technologies to the development of therapeutics for a variety of diseases, both common and rare.

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