Author Archives: Christina Butterworth

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.

#4HLFamilies Zoom Features Family Stories

On July 18, 2021, three parents of children affected by 4H (POLR3-Related) Leukodystrophy shared their children’s and families’ stories. They discussed the stories of their diagnoses, challenges and successes, and key choices they’ve made in their children’s medical care. Their stories highlight the broad spectrum in the effects of 4H and the resilience of our patient and families community.

Following the #4HLFamilies stories, parents discussed questions they have about particular care choices they’ve made or are considering.

Ron Garber from the Yaya Foundation also shared updates about the recently launched 4H Leukodystrophy Data Collection Program, an exciting upcoming grant announcement, and preliminary plans for a 4H Family and Scientific Conference in 2022.

Click to see the recording of the #4HLFamilies call:

Please join us for the next #4HLFamilies Zoom on Sunday, September 19th at 4:00 pm ET / 1:00 pm PT.

Whether you are newly diagnosed or have been caregiving for someone affected by 4H for years, all are welcome to the Yaya Foundation’s bi-monthly #4HLFamilies Zoom Hangouts. Please register and join us at the next discussion on Sunday, September 19th.

Once registered, you will receive an email with Zoom details. Have questions or an idea about an upcoming #4HLFamilies topic? Email info@yayafoundation4hl.org.

We look forward to connecting with you!

Next #4HLFamilies Zoom Hangout is Sunday, July 18th

The Yaya Foundation hosts #4HLFamilies Zoom Hangouts bi-monthly to gather our 4H Leukodystrophy community together on a regular basis. Foundation updates and priorities are shared with families as well as engagement opportunities such as participating in research or volunteering with the foundation.

Perhaps most important to these Zoom Hangouts is the chance for families affected by 4H to gather and share with each other.

Please join us this Sunday, July 18th at 4:00 pm ET / 1:00 pm PT for the next #4HLFamilies Hangout.

After an update on the 4H Leukodystrophy Data Collection Program, 4H caregiver Tammy Bock will kick off a discussion with some of our community’s “veterans” to share their stories and answer questions. The group will also discuss self care.

Once registered, you will receive an email with Zoom details. Whether you’re a 4H veteran or newly diagnosed, we look forward to connecting with you!

The 4H Leukodystrophy Data Collection is Open!

Participate in Research via Data Collection

The Data Collection Program is open and we invite you to participate by sharing your data, which is critical for research.

When you participate in data collection, sometimes called a disease or patient registry, you’ll help accelerate research and the development of new drugs and other therapies.

Collecting data is an essential step on a rare disease research journey and an important way for patients and their caregivers to contribute to advancing care for their communities.

To share your data, please visit the Data Collection portal:

On a recent family call, Dr. Nicole Wolf, one of the world’s leading clinician scientists of 4H Leukodystrophy spoke to the importance of data collection. She mentioned that this data informs the natural history of a disease and can be helpful in several ways, including:

  • Counseling families what to expect of the disease
  • Understanding the basic disease mechanisms
  • Evaluating the effect of treatments
  • Quickly identifying possible clinical trial candidates

To hear more about the importance of data collection and about our partner, RARE-X, a 501(c)3 nonprofit, you are invited to watch our Info Session on this topic:

Launching the 4H Leukodystrophy Data Collection Program

Register for Info Session to Learn More

Collecting data is an essential first step on a rare disease research journey and an important way for patients and their caregivers to contribute to advancing care for their communities.

On a recent family call, Dr. Nicole Wolf, one of the world’s leading clinician scientists of 4H/POLR3-related Leukodystrophy spoke to the importance of data collection. She mentioned that this data informs the natural history of a disease and can be helpful in several ways, including:

  • Counseling families what to expect of the disease
  • Understanding the basic disease mechanisms
  • Evaluating the effect of treatments
  • Quickly identifying possible clinical trial candidates

Launching on June 21st, the Yaya Foundation is excited to announce a new 4H/POLR3-related Leukodystrophy Data Collection Program (also called a disease registry). The Foundation has partnered with leading rare disease data collection experts RARE-X.

To learn more about the Data Collection effort and benefits, please register for an upcoming Information Session on June 16th.

To hear more from Dr. Wolf on the importance of data collection, you are invited to watch her presentation on this topic:

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.

Yaya Foundation Hosts Its First Global Seminar

Scientific Seminar Focuses on RNA Polymerase III

An international collaborative of leading scientists gathered on April 15, 2021 to discuss RNA Polymerase III structures, mechanisms and potential for intervention. Structural Biology Professor Alessandro Vannini of both the Human Technopole Institute in Milan and the Institute of Cancer Research in London presented the leading science of what is known about POL III as well as engaging the group of forty scientists from around the world on leading basic science questions that are yet to be answered.

Key themes included…

  • Several labs around the world are studying and interested in RNA Polymerase III (POL III) and there is now a better understanding of the POL III structure
  • POL III is implicated in countless other diseases, including cancer and immunodeficiencies
  • The next steps are to identify which basic research questions are most valuable to answer regarding its pathogenesis; this might include:
    • Molecular mechanisms of pathogenesis
    • Tools to recapitulate 4H Leukodystrophy
    • Various therapeutic intervention such as gene therapy
  • Intentional and strategic collaboration and organization of our resources related to studying POL III will serve our community best in accelerating therapeutic discovery

“It’s great having this forum here to discuss collaboration to divide and conquer. Ultimately, as basic research scientists, we have to do our best to drive this to potential benefit for this community.

Professor Alessandro Vannini,
Human Technopole Institute in Milan and
The Institute of Cancer Research in London

This highly informative and insightful presentation exceeded expectations of engagement and collaboration amongst the seminar group and the Yaya Foundation is incredibly appreciative. Convening in this manner proved very productive in many ways and the Yaya Foundation looks forward to continuing to nurture and even kickstart this type of collaboration in upcoming seminars.

The Yaya Foundation believes that discovering therapies for those affected by 4H Leukodystrophy takes collaboration from all of us. Please engage with us if you have questions about this seminar via info@yayafoundation4hl.org. And if you would like to be informed of future scientific seminars, or if you have an idea for a future seminar topic, please send us your contact information via our website.

Again, a special Thank You to Professor Alessandro Vannini and Sebastien Fribourg for kicking off our scientific seminars and sparking further collaboration!

Proud to be #RareAsOne

Celebrating Year One of the Chan Zuckerberg Initiative Grant

The Yaya Foundation for 4H Leukodystrophy is celebrating one year of growth and accomplishments thanks to the joint efforts from our partners at CZI and collaboration with our Rare As One network.

“We are so grateful to the Chan Zuckerberg Initiative and the entire #RareAsOne family for the opportunity to be a part of CZI’s Rare As One program. The grant, through its training and capacity building, networking, and funding, has changed the trajectory of our disease community’s efforts to collect data to improve understanding of 4H (POLR3-Related) Leukodystrophy and accelerate the discovery of therapies that will help people affected by 4H live longer, better lives. Thank you, CZI!”

Ron Garber, Co-founder & President of the Yaya Foundation

We wanted to mark this milestone by highlighting some of the accomplishments that the Yaya Foundation has made in the last year with the support of the Rare As One grant and community:

  • Launched the 4H Leukodystrophy Research Network (or #4HCN), a collaborative research network of researchers, clinicians, and patients/families from different disciplines and labs across the globe.
  • Hosted 2-day working meeting of #4HLCN focused on discussing current state of science and potential pathways to better disease understanding and therapeutic discovery.
  • Created a strategic Research Roadmap toward developing a cure and therapies for 4H and started executing on it.
  • Hosted several #4HLFamilies Zoom calls at which families and caregivers connected, sharing knowledge and best practices, and just getting to know and connect with each other.
  • Created significant organizational capacity, building a professional, mission-driven team, streamlining organizational policies and practices, and working towards a sustainable fundraising model.

The Yaya Foundation is proud to be #RareAsOne and we look forward to continuing to accelerate research and support our community of families affected by 4H.