Tag Archives: POLR3-related Leukodystrophy

4H Leukodystrophy: Launch of a Proof of Concept Study on a Potential Gene Therapy


The Yaya Foundation for 4H Leukodystrophy, the Research Institute of the McGill University Health Center, the Montreal Children’s Foundation and the University of Massachusetts Medical School Join Forces in a New Six-Figure Project Seeking Treatments for Children Affected by this Rare Disorder


4H gene therapy collaboration

MINNEAPOLIS (September 1, 2021) — The Yaya Foundation for 4H Leukodystrophy, the world’s only organization dedicated to fighting for people affected by 4H (POLR3-Related) Leukodystrophy, is partnering with Dr. Geneviève Bernard of the MyeliNeuroGene Lab at the Research Institute of the McGill University Health Centre (RI-MUHC) and Drs. Guangping Gao and Jun Xie of the Horae Gene Therapy Center at the University of Massachusetts Medical School to develop 4H (POLR3-Related) Leukodystrophy mouse models and study a potential gene therapy for 4H Leukodystrophy.

4H Leukodystrophy is a rare, progressive, genetic neurological disorder that primarily affects children and for which there is not yet a treatment or cure. This six-figure commitment from the Yaya Foundation will enable researchers at the MyeliNeuroGene Lab and Horae Gene Therapy Center to develop and characterize a suite of mouse models that will serve as critical research tools for the 4H Leukodystrophy disease community, as well as develop a pre-clinical gene therapy proof of concept that will help advance discovery of a gene therapy that could one day help patients affected by 4H Leukodystrophy achieve better outcomes.

“I am excited to be partnering with Dr. Gao and the Yaya Foundation on this study,” said Dr. Bernard, a scientist in the Child Health and Human Development Program at the RI-MUHC. “It is only with collaboration between patients, families and researchers with complementary skill sets that we will be able to drive better outcomes for these patients that I care so much about. I am extremely grateful to the Yaya Foundation for their generous commitment to the Montreal Children’s Hospital Foundation in support of this study, which will transform lives.”

“Gene therapy directly targets the underlying disease biology, which I believe has the potential to lead to transformative treatments,” said Dr. Gao. “I am thrilled to be working with Dr. Bernard and the Yaya Foundation on discovery that could bring these kinds of treatments to patients affected by 4H Leukodystrophy.”

Drs. Bernard and Gao each participate in the 4H Leukodystrophy Collaboration Network (#4HLCN), a global research collaborative convened by the Yaya Foundation and comprised of patients, families, researchers, and clinicians working together to accelerate discovery of therapies that will help people affected by 4H Leukodystrophy. The #4HLCN works together as a community to identify and prioritize the highest impact research, find the best people in the world to conduct that research, execute studies, and rapidly disseminate and build upon findings.

“This project is exactly the type of collaboration that the #4HLCN seeks to promote,” said Ron Garber, President of the Yaya Foundation. “We are thrilled to enable partnership among Dr. Bernard, one of the world’s foremost 4H Leukodystrophy experts with Dr. Gao, a preeminent gene therapy leader from outside our disease community. This collaboration will generate important research tools and early data that will de-risk 4H therapy development and make progress towards our ultimate goal, which is a therapy or cure that will enable people affected by 4H Leukodystrophy to live longer, better lives.”

Work on the project will begin immediately. Patients and families interested in learning more about the project are encouraged to contact the Yaya Foundation for 4H Leukodystrophy at info@yayafoundation4HL.org.

This project has been made possible in part by grants from the Chan Zuckerberg Initiative Rare As One Project and the Tallman Family Charitable Fund.

About the Yaya Foundation for 4H Leukodystrophy 

Founded by a group of parents of children with 4H Leukodystrophy, the Yaya Foundation is the only organization in the world dedicated to fighting for patients and families affected by 4H Leukodystrophy. Its mission is to accelerate discovery of therapies and cures that will enable patients affected by 4H Leukodystrophy to live longer, better lives and to provide educational and emotional support to affected families. For more information, please visit www.yayafoundation4HL.org.

About MyeliNeuroGeneLab at Research Institute of the McGill University Health Centre

The MyeliNeuroGene Lab, located at the Research Institute of the McGill University Health Centre in Montreal, Canada, is led by Dr. Geneviève Bernard. Dr. Geneviève Bernard is a pediatric neurologist and clinician scientist. She is in charge of the first and largest leukodystrophy clinic in Canada. She has built a comprehensive research program on leukodystrophies, focusing on 4H (POLR3-related) leukodystrophy, from patients’ bedside, to bench and then back to bedside.

About Horae Gene Therapy Center at the University of Massachusetts Medical School

The Horae Gene Therapy Center at the University of Massachusetts Medical School is dedicated to developing therapeutic approaches for rare inherited disease for which there is no cure, utilizing state of the art technologies to either edit mutated genes that produce disease-causing proteins or introduce a healthy copy of a gene if the mutation results in a non-functional protein. UMass Medical School is consistently ranked as one of the leading medical schools in the nation for primary care education and is ranked 21st nationally in research funding from the National Institutes of Health.

What is gene therapy?

Gene therapy is a method that uses genetic material to treat disease.  This unique treatment addresses the underlying genetic cause, rather than treating the resulting symptoms.  This approach opens up new possibilities to treat or even cure diseases for which few or no other options are available; in particular, it provides hope for rare genetic disorders like 4H Leukodystrophy.

Gene therapy for humans is still an experimental technique; only a few gene therapies are currently approved by the U.S. Food and Drug Administration (FDA) to treat patients. However, a lot of progress has been made over the last decade and there are now many ongoing efforts, both in industry and academia, to develop gene therapies for rare disorders.

Gene therapy for 4H Leukodystrophy

4H Leukodystrophy is caused by mutations in genes that are the recipes for making proteins for an essential cellular machinery (RNA polymerase III). By delivering a functioning copy of the mutated gene directly to cells, we hope to repair the body’s ability to make those proteins. The replacement gene compensates for the nonfunctioning copies and bypasses the underlying cause of the problem.

This study

To deliver the therapeutic genetic material correctly, it needs to be packaged into a vector that can find and attach to the right cells (in our case oligodendrocytes in the brain). Think of wrapping and addressing a parcel for delivery. This delivery method is similar to how a virus enters our cells, but without the infectious part.

Drs. Guangping Gao and Jun Xie are the researchers who work on developing the right vector for our purpose. The vector must then be tested in appropriate disease models to see whether it works as anticipated (known as “Proof of Concept”). Dr. Geneviève Bernard’s laboratory is responsible for generating a mouse model for 4H Leukodystrophy and then performing those tests. The Yaya Foundation’s grant will provide the resources for this important work.

What comes next?

Proof of Concept, mentioned in the previous section, is the very first step on the road to a therapy. If successful, this is followed by the preclinical stage which includes further research and extensive testing to ensure safety. If all goes well, an application is submitted to the FDA to allow testing in humans and to proceed to clinical trials. This is a promising step toward finding a treatment for 4H Leukodystrophy.

Learn more about gene therapy

  • Gene Therapy at a Glance: Quick overview of gene therapy with AAV vectors, the same kind of vector that is used in our study

Join Us September 19th for the Next #4HLFamilies Call

The next #4HLFamilies call hosted by the Yaya Foundation is scheduled for Sunday, September 19th at 4:00 pm ET / 1:00 pm PT. Please join us for:

  • updates from the Foundation
  • discussion on a variety of 4H-related topics, led by Tammy Bock
  • to connect with others in our community

Please use this link to register: https://yayafoundation4hl.kindful.com/register/zoom-hangout-for-4hlfamilies-sunday-september-19th-2021

We look forward to seeing you! If you have questions or topics for our call, please email christina@yayafoundation4hl.org.

Yaya Foundation Welcomes Dr. Nicole Wolf to Family Call

Patient advocacy groups like the Yaya Foundation can play many roles – educating, raising funds and driving research strategy, advocating for, and providing support services to our families. One of the important support services comes in the form of bi-monthly #4HLFamilies Zoom calls – event details can be found on our Facebook page.

On May 16th, the Yaya Foundation invited a very special guest to join the #4HLFamilies call – Dr. Nicole Wolf of the Amsterdam Leukodystrophy Center and the Amsterdam University Medical Center. Dr. Wolf is one of the world’s leading clinician scientists of 4H/POLR3-related Leukodystrophy.

Several important topics were presented including the history of 4H Leukodystrophy, how this rare disease is described and diagnosed, both typical and atypical clinical course, and current research in 4H Leukodystrophy. Dr. Wolf also described the critical importance of data collection efforts, or disease registries, in further understanding rare diseases, designing clinical trials and identifying possible clinical trial candidates. The families also discussed topics important to them, including the Covid vaccine.

The Yaya Foundation is incredibly grateful to Dr. Wolf for her valuable time, insight and care for families affected by 4H Leukodystrophy. You can watch the discussion here:

“It is so nice to have Dr. Wolf share time with us, she diagnosed my daughter 8 years ago and was part of the team that discovered the syndrome. Without her, hundreds of families would still be searching for answers. Dr. Wolf gave us hope that some day there will be treatments or even a cure for 4HL.”
— Tammy

Finally, thank you to our families affected by 4H for actively engaging in the hosted #4HLFamilies calls.

The Yaya Foundation is committed to hosting family calls and events that are relevant for everyone, including those newly diagnosed. Please join us for the next call on Sunday, July 18th.