Giving the Gift of Health

Three organizations give updates on their rare disease research – and what you can do to help

NOTE: This article is also available in another language (FRANÇAIS CANADIEN).

Foundation for Angelman Syndrome Therapeutics (FAST)/Cure Angelman

We have spoken before with Dr. Allyson Berent, mother of Quincy and Chief Science Officer for FAST. When her daughter was diagnosed with Angelman syndrome (AS), Allyson used her scientific background to learn all she could about the debilitating disease and began her quest for a cure.

“The past year has been really tremendous for FAST – we’ve advanced more research programs through proof of concept toward human candidate and IND-enabling studies than we ever have before,” she said. “It has been an incredible time for research for Angelman syndrome that is actually translatable to human clinical application. There are now three disease-modifying therapies in clinical trials – one of which was from the company we [FAST] started, GeneTx Biotherapeutics.”

This year also saw the acquisition of GeneTx by Ultragenyx – which Allyson says is a positive step forward not only for the company, but also for the other drug candidates under consideration. The goal of GeneTx was to bring the candidate forward as quickly and safely as possible in order to make it very attractive to a larger company, who would have the resources to carry it across the finish line.

Numerous disease modifying therapeutic programs are being advanced into IND-enabling studies, and FAST is robustly supporting a novel gene editing program, as well as some new downstream targeted therapies, all of which was made far easier with the funds from the GeneTx acquisition.

Allyson is also very proud of the new biorepository of stem cells for all genotypes for AS – which will prove an invaluable resource for any researcher to ensure that we de-risk and test all genotypes for Angelman syndrome and bring meaningful therapies to everyone around the world.

Finally, this year saw the founding of the FAST Global Search and Rescue Initiative, which aims to seek out patients around the world who have been diagnosed with AS, or who may have AS and are misdiagnosed, and connect them with researchers, doctors, or potential clinical studies to help advance treatments all around the world. As she knows from personal experience, the community available to a family experiencing AS is life-saving on so many levels. This community brings knowledge, which brings power to the family and helps decisions families need to make for loved ones living with AS, and this resource should be made available to anyone worldwide who wants it.

Beyond this initiative, the goal of FAST remains the same: advance as many promising drug candidates as possible, while preparing to reach as many people as possible that are impacted by AS. Each candidate can take over 100 million dollars to advance to approvals, so the task is not easy. For now, of the 25 candidates that are advancing toward clinical trials, FAST is robustly supporting 13.

Find out more about what you can do to help here.

Cure SPG50

In April 2019, Michael Pirovolakis was diagnosed with an ultra-rare neurodegenerative disease called SPG50 – or Spastic Paraplegia Type 50 – a genetic defect in which the body fails to produce a certain protein essential for development. His parents learned that Michael, not yet 2, would initially lose muscle tone in his feet and eventually be completely paralyzed.

Like many families dealing with a rare disease, Michael’s parents sprang into action. A month after Michael was diagnosed, his father Terry flew from their home in Canada to Washington DC and crashed a conference intended for gene therapy researchers, and over the course of two days met with several leading experts in the field as well as experts from the US National Institutes of Health and US Food and Drug Administration. His dogged pursuit of a treatment and an aggressive campaign to raise US$3.5 million to pay for the research eventually brought success.

Last March Michael, now age 4, began treatment at The Hospital for Sick Children (SickKids) in Toronto with a gene therapy that hopefully will slow the progression of his condition. It took over a dozen research institutions and laboratories across the globe to develop the treatment, including Charles River Laboratories. While it is still unclear at this point how long it will be before the new nerve cells start functioning properly in Michael, researchers are hopeful they will see signs of progress.

There was more good news this year. The US Food and Drug Administration granted approval to proceed with a clinical trial of the gene therapy drug given to Michael in Canada. The goal is to show efficacy in more than 10 children and then eventually get full FDA approval for the drug, known as Melpida. The clinical trial is being run by the University of Texas Southwestern Medical Center, an early collaborator with SPG50. The plan is to dose the first child enrolled in the US trial before the end of February 2023, says Terry.

But the sheer cost of funding these trials, often solely on the backs of disease foundations begun by parents like Michael’s, is daunting. Manufacturing a gene therapy is a complex, lengthy and expensive process compared to a small molecule drug or even other biological drugs. Administering the drug is also pricey. With pharmaceutical companies largely absent from these ultra-rare diseases, it becomes the responsibility of parents and non-profit foundations to raise the funds.

That is not stopping Terry and the foundation he started to help his son. “Our goal is to treat as many as we can and move this forward so that every kid with SPG50 can benefit from it,” said Terry.

Log on here to learn more about SPG50 and to donate to the foundation.

Grace Science Foundation

In the last few years, the Grace Science Foundation has made amazing strides towards the founders’ initial goal: to develop a cure for everyone fighting NGLY1 deficiency, which includes their own daughter. When Grace was diagnosed, the Wilseys pledged to help everyone in the community that they suddenly found themselves a part of.

This year marked their first IND submission, which is a concrete step toward getting their drug candidate into human trials.

“It is obviously a huge accomplishment for the team,” said Matt Wilsey, Grace’s father. “They’ve been working around the clock to get all the pieces in. I think most people who aren’t in life sciences have no idea.”

The milestone is not only a hopeful victory for Grace and the other people affected by NGLY1 deficiency, but also a potential benefit to other diseases. The drug is comprised of an adeno-associated virus (AAV) administered directly to the brain via intracerebroventricular injection (ICV), which is an uncommon delivery system that overcomes the issues of drug delivery to the brain.

The administrative route is not without its dangers, which will be fully explored as the candidate progresses through the FDA. However, it has the benefit of a smaller dose getting exactly where it needs to go and lessens the danger of toxicity when a higher dose is required to cross the blood-brain barrier. The more this method is researched, and the more AAV candidates are explored, the more hope there is for patients experiencing similar needs from different diseases.

“The FDA has been very supportive and collaborative, which I didn’t expect,” said Matt. “That is very similar to what we have experienced with Charles River, where a rising tide lifts all boats. I think Charles River fundamentally believes that, and we have been really fortunate with our partners.”

Wilsey is naturally eager to continue this work that could help his disease community, but he is also excited by the prospect of helping others along the way. He credits his team of scientists, which this year gained its fourth Nobel Prize with the award in chemistry being given to Carolyn R. Bertozzi. As Wilsey says, he would put his team up against any disease.

As for Grace, like many children she has experienced a unique situation in the last few years with COVID. Like many special needs children, the isolation caused her to lose some skills that had been gained. However, she is back at school and is gaining back what she lost.

“She is the only kid at her school allowed to ride an adaptive bike, so she is kind of a celebrity on campus,” Matt said. “She’s still very much with us. She is aware of people, and books, and songs, and she gives me the motivation to keep going.”

Find out more about Grace Science here.