Author: Laura Hameed

Madrid, February, 2021.- A new treatment for the rare and fatal neurodegenerative disease Niemann Pick C is closer. University College London (UCL) has just started a preclinical study that will make it possible in the future to apply gene therapy to patients in a clinical trial. This project is done in collaboration with the Columbus Foundation (FC)/Columbus Children’s Foundation (CCF), Viralgen Vector Core and UK MRC (UK Medical Research Council)

Niemann Pick disease type C (NP-C) is an inherited lysosomal storage disorder, in which the systemic accumulation of intracellular lipids leads to a progressive and fatal disorder. “It is an inherited disease caused by a defect in the proteins that transport cholesterol. This defect is caused in 95% of cases by mutations in the NPC1 gene, resulting in accumulation of cholesterol and other fats in the liver, spleen or lungs. Neurological symptoms such as clumsiness in walking, difficulties in swallowing and eating, usually appear later in disease “, explains the president of the Columbus Foundation, Damià Tormo.

Healing through gene therapy: replacing the faulty gene

Frequently this pathology manifests itself in an early age and affects one in every 100,000 people. It is a rare disease for which there is little research in the world. One research group is at University College London (UCL), led by Prof. Ahad Rahim. So far, studies in Prof. Rahim’s laboratory, applying adeno-associated virus (AAV) –mediated gene therapy as a vector carrying the correct gene have shown therapeutic benefit in preclinical studies. “Currently there are no good treatments for this disease and the premature death in these children makes it necessary to find an effective treatment urgently. Prof. Rahim’s group has shown that gene therapy can be a way of hope for these patients and our challenge is to help this research until a treatment is achieved,” adds Tormo.

AAV-mediated gene therapy has great potential to treat NP-C by preventing or slowing neurodegeneration and subsequent fatal neurological disease. “During previous studies in animals, we have shown that direct administration to the brain of an AAV9 vector expressing the human NPC1 gene in neurons has allowed the long-term prevention of neurological symptoms accompanied by the prolongation of the animal’s life. With this new phase of research, we want to improve therapeutic efficacy and move towards the preparation for clinical trials in patients “, explains Prof. Ahad Rahim. “Our challenge is to bring this new gene therapy to Niemann-Pick type C1 (NPC1) patients within a few years“, he concludes.

Viral vectors created in Spain

For the manufacture of the treatment, UCL has FC/CCF as an ally and the support for years from the Association Niemann-Pick Fuenlabrada. Funding for these new activities to be carried out took place around an initiative called “Marta’s trip”. Marta is a girl affected by NPC and her family promoted an activity together with the FC/CCF that managed to raise enough money to undertake this project. In this way, the Foundation will have access to the production of viral vectors and also funding from the UK MRC to help carry out toxicology studies, which represents an important boost to the work plan of Prof. Rahim’s team. The gene therapy vector will be manufactured at Viralgen Vector Core, which is one of the world’s leading companies in the manufacture of viral vectors domiciled in San Sebastián, thanks to the agreement that the Foundation has with this company. Under this agreement, Viralgen provides its knowledge, access to capacity and manufacturing of AAV vectors at a significant discount for clinical programs in rare diseases for which there is limited commercial therapeutic availability. “This contribution of material by FC/CCF and Viralgen is a key and necessary advance to be able to bring the drug to our children since it is one of the great bottlenecks in this project“, comments Marta’s father, Ignacio de la Serna.

Partnerships to develop drugs against rare diseases

FC and their US based sister foundation, CCF, have already made important advances to accelerate other treatments for rare diseases with gene therapy, such as L-amino acid aromatic decarboxylase deficiency (AADC deficiency) or infantile Parkinson’s disease. To date, more than 25 children from around the world have received treatment in the centers in Europe and the US with excellent results that have radically improved their quality of life and that of their families. In addition, the organization has already sealed several alliances with other associations with the aim of promoting internal research programs that currently exist for rare diseases and providing therapeutic access to affected people. For example, we have developed exciting partnerships with the American NGO Cure Rare Disease, the Canadian NGO CureSPG50, and the New York-based biotech company Phoenix Nest to address Sanfilippo type C disease, among others.

The Medical Research Council is at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers’ money in some of the best medical research in the world across every area of health. Thirty-three MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomized controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. The Medical Research Council is part of UK Research and Innovation.

TORONTO — A new gene therapy for an extremely rare disorder has offered two Canadian children a new chance at life, allowing them to move on their own after years of being trapped within their own bodies.
The disease is called AAV deficiency, and known more commonly as ‘pediatric Parkinson’s’. It’s a debilitating genetic disorder that effectively cuts off communication between cells in the nervous system, affecting movement

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For Rian, a little girl from Toronto, this meant that at four years old, her body was still like a newborn’s — she couldn’t support her own head, eat on her own, or play the way other children could.
“She had absolutely no functional, purposeful movement,” Rian’s mother, Shillann Rodriguez-Pena, told CTV News. “It essentially was like her body was a prison that she was trapped in. And we could see the sparkle in her eye, we could always see that she was in there and the desperation of trying to get her out, and how to help her out — it was torturous, truthfully.”

Those who have pediatric Parkinson’s also suffer from episodes called oculogyric crises (OGC), in which they experience muscle spasms, uncontrollable rolling of the eyes, agitation and even pain.
In a post on her Facebook documenting Rian’s journey battling this disease, Rodriguez-Pena wrote that Rian suffered from OGCs every three to four days, and that her episodes lasted up to eight hours.
Rodriguez-Pena told CTV News that it was hard to see her daughter suffer.
“She was going through panic attacks and just the sheer frustration of wanting to
do something and her body not allowing her to,” she said. “Because cognitively, she understands so much.”
Historically, there has been no treatment, just disability and an early death, with the disease often proving fatal.

But in September of 2019, Rian became one of the first recipients of an experimental gene therapy. And within weeks of treatment, she began to move. First it was just her head. Then she could hold objects. Now, at six years old, she can sit on her own. And her mother is blown away. “It really is modern day miracle stuff,” she said. “It really is. The science is absolutely miraculous. “We prayed for years […] to be able to see it for our girl, and it’s incredible.”

In a recent video of Rian’s progress, posted in January, she opens a cupboard door on her own while sitting on the floor in her family’s kitchen. Smiling and laughing, she spins around and reopens the cupboard a few times while her mother, filming, narrates. “New skill alert!” her mother praises her in the video. “Are you so proud you figured that out?”

And after the treatment, those paralyzing seizures never returned. It’s incredible progress, according to Dr. Saadet Andrews, one of many doctors who used to treat Rian in the early years of her life, when she was in and out of the hospital constantly.

“The improvements since the gene therapy is amazing,” he said. “She keeps improving very quickly. To give you an example, from […] nine months to almost four years of age, she didn’t do anything. And from a few months of the gene therapy, she just started holding her head and then started slowly sitting up to show us some great improvements.”

How the new gene therapy works is that the genes needed to restore movement are actually put into AAV viruses, and then injected deep into the brain. Once there, the DNA is taken up by cells, and starts correcting the defect.

The therapy is so new that only 23 children worldwide have received this treatment. All of them were treated by Dr. Krystof Baniewicz, one of the world’s leading experts in pediatric Parkinson’s.
“I never expected this to be to be as significant as what we are seeing,” Bankiewicz told CTV News.
Bankiewicz is a professor and the director of the Brain Health and Performance Center at the Ohio State University College of Medicine. He described the first ideas that would eventually become this gene therapy in a paper 25 years ago.

“[I’ve] devoted decades of my life to develop this technology and [I’m] very, very pleased that they can change people’s lives,” he said.

“Without the gene therapy, they would have never been able to achieve the milestones which they have had so far.”

One of the big positives it that so far, it appears that only one treatment is necessary.
“It’s a one-time treatment, as far as I can tell,” Bankiewicz said. “No one has plateaued, they keep on improving.”

Rian isn’t the only Canadian to have benefitted from this new therapy. A seven-year-old in Vancouver, B.C., is now learning to walk after her life-changing treatment.
Jasmine suffered from OGC up to three times a week before her surgery, her parents told CTV News in an email.

“Our life was dark,” her father, Seila Hok wrote, adding that he had no time to think of his own health, only his daughter’s. He and his wife would take turns to sleep at night so that one of them could keep an eye on Jasmine and make sure she was okay. They suffered abusive comments from their community for having “a kid like Jasmine,” which was heartbreaking for them.

The family was able to send Jasmine to receive the new gene therapy in Ohio as part of a clinical trial funded by the lab.

It’s been 18 months since she received the therapy, and Jasmine is “a different Jasmine,” according to her family.

“She is happier, healthier,” Hok said, adding that she no longer suffers from OGCs, and is able to sit, roll around and eat.

A recent video of Jasmine shows her sitting on an exercise ball on her own, smiling, and vocalizing and grabbing a toy.

In another video sent by the family, she is being trained to walk.

Dr. Bankiewicz is awaiting publication of his preliminary study in the coming weeks.
But although this new therapy is extremely promising, there are still numerous barriers to delivering this care, one of them being cost. Therapies for rare diseases aren’t profitable, so all this is funded by donations, fund raising and charities, with many other children waiting for treatment.

Rian received her gene therapy not in the U.S., but in Poland, where Bankiewicz — who is originally from Poland — was offering surgeries as part of “compassionate use” clinical trials for those who could not wait for the therapy to be offered in the U.S.

“Although it was a risky surgery — it was an eight and a half hour brain surgery in
a foreign country — the risks associated to not having the surgery were far more terrifying,” Rodriguez-Pena said.

She added that it cost the family 45,000 euros — just under $68,000 — to make the trip for the treatment which Dr. Banks says was done not for profit. Some of it was their own savings, while some was raised through websites like GoFundMe.

“And that’s actually quite a modest price,” she said. “Because when you look at other rare diseases such as [spinal muscular atrophy], the price point is astronomically larger.”

Some charities, such as the Columbus Children’s Foundation (CCF), help families battling rare diseases to gain access to new treatments like this one. AAV deficiency is one of the ultra-rare diseases that CCF is trying to help cure by supporting new therapies.

“We want to make sure that what happen to Jasmine and Rian happens for other children,” Laura Hameed, executive director of CCF, told CTV News in a phone call.

“These therapies are clinically promising, but don’t get the interest of the biotech industry because they are too small, so non-profit is the best way to make sure they are advanced.”

Another barrier is that so few people are aware of these type of diseases. And that’s one reason that families like Jasmine and Rian’s are coming forward to share their stories.

“There’s only 130 kids approximately in the world with our disease,” Rodriguez-Pena said. “And the fact that there was a treatment that could so drastically change [Rian’s] quality of life — I feel like there’s a lot of value in sharing that story.”

“There are still so many kids with AAV disease [who] need to get surgery,” Hok said, adding that the most important thing is for others to learn about this disease and about the new gene therapy that can turn things around.

These families have had their childrens’ lives transformed for the better — and now they’re hoping to help others transform young lives too.

“I think gene therapy as a technology and medical procedure is gaining [a] tremendous amount of acceptance right now, and I think success is being seen in multiple diseases,” Bankiewicz said. “There are also other disorders outside of the brain which could benefit from this technology.”

He’s already working on trying to apply this gene therapy to adults with Parkinsons, and hopes that they can expand the current gene therapy to additional sites, so more children can be helped.

Rodriguez-Pena said that the family thinks of Rian’s surgery day as almost a second birthday.
“It’s as if she was reborn in so many ways,” she said.

After she was treated, Rian got a puppy, who happened to be born on the same day that she had her surgery.

So what is the puppy’s name? “Banks”, of course, after the doctor who performed the miracle procedure.

Organizations unite with world-class scientific and AAV technology leaders to find a cure for life-altering and fatal ultra-rare disease

Brooklyn, NY and Raleigh, NC (Oct 28, 2020)—Phoenix Nest, a New York based biotechnology company will partner with Columbus Children’s Foundation (CCF) to advance the development and manufacturing of a potential gene therapy treatment for Sanfilippo syndrome type C, an ultra-rare metabolic disorder, also referred to as MPS IIIC. 

It is estimated that only 1 in a million children are born with MPS IIIC with less than 500 children worldwide known to have this devastating disease. Individuals affected by this type of Sanfilippo syndrome lack a single enzyme necessary to break down long chains of sugar molecules called mucopolysaccharides (also known as glycosaminoglycans or GAGs). These GAGs are left to build up in every cell of the body causing catastrophic effects to the CNS and throughout the body. Children appear normal at birth and it isn’t until the children fail to meet typical milestones that parents become worried. As the disease progresses, children lose all their skills including the ability to talk, walk, and swallow. The disease is terminal and there is no current treatment.

“MPS IIIC, like many ultra-rare diseases, is not being addressed by large biotech and pharma companies due to small patient populations and the significant investment required for research, development and manufacturing,” commented Laura Hameed, Columbus Children’s Foundation managing director. “This is the basis for our mission and the formation of a nonprofit biotech foundation focused on accelerating development and access to curative gene therapies for children with ultra-rare genetic conditions at an more affordable cost that does not lead to access issues.”

Phoenix Nest founder and Chief Financial Officer, Jill Wood, is a fierce patient advocate and mother whose son Jonah, along with approximately 500 children around the world, suffer from this rare condition.  Jill, along with her husband Jeremy Weishaar and a renowned scientific advisory board, have facilitated and funded research for potential enzyme replacement therapies (IIID), chaperone therapy (IIIC) and stem cell/gene therapy (IIIB).

According to Ms. Wood, “Like many small biotechs, we lack the funding and expertise to advance potential treatments and cures for this devastating disease, but we know a cure is in sight. Working collaboratively with the Columbus Children’s Foundation, we will gain access to world-class scientific and manufacturing expertise, saving millions of dollars and time, a luxury my son Jonah and many children like him do not have.”

The partnership between CCF and Phoenix Nest is a leading example of the effort needed to bridge the translational gap that slows or impedes many rare disease programs with curative potential. The nonprofit biotechnology foundation model pioneered by CCF plays an important role in the rare disease ecosystem by partnering with leading researchers and contract development and manufacturing organizations (CDMOs). These include companies such as Viralgen Vector Core, a leading manufacturer of adeno-associated virus (AAV) medicines, and Asklepios BioPharmaceutical (AskBio), a company revolutionizing life-saving gene therapeutics and genetic medicine technology.

“This is the third program we will put into development or manufacturing in the last two months,” according to Hameed. “This partnership reflects exceptional progress toward our goal of accelerating treatments for programs that are scientifically promising, but not commercially viable. We believe no child should be left behind when cures are in reach and are thrilled to partner with organizations like Phoenix Nest to advance our mission to bring gene therapy cures to children with the urgency they deserve.”

About Columbus Children’s Foundation (CCF)

CCF’s mission is to ensure equitable and affordable access to the most effective gene therapy solutions for children with ultra-rare genetic diseases. CCF uses a nonprofit model to partner and accelerate gene therapy treatments for programs with very small patient populations that are often overlooked because the economics don’t add up for those using a traditional commercial development model. Through strategic partnerships with other foundations, industry leaders, patient groups and philanthropic donors; CCF aims to bring the scientific and funding resources together on behalf of the children and families who must endure the devastating outcomes of ultra-rare diseases. CCF accelerates hope and transforms the lives of those fighting these devastating diseases.  Learn more at www.columbuschildren.org 

About Phoenix Nest

Phoenix Nest is a bespoke virtual biotech with one mission, to provide a treatment for the children suffering from Sanfilippo syndrome. Founded by a mother of a Sanfilippo child, Phoenix Nest has sponsored various research initiatives with leading scientists and medical experts to find treatments and cures for all types Sanfilippo syndrome. Led by parents of children with Sanfilippo syndrome, the company operates first and foremost in the best interest of children in critical need for a cure. http://www.phoenixnestbiotech.com/