Charity and NIH funding related to Zolgensma

June 14, 2019

​​Zolgensma, the Novartis brand name for the new $2.1 million gene therapy for treatment of Spinal Muscular Atrophy (SMA), appears to be a remarkable medical breakthrough treatment. It is also, like all of the new cell- and gene-therapies, one that was developed with considerable support for non-profit entities, including, in this case, several charities and the NIH.

The intellectual property rights for Zolgensma were licensed from the University of Pennsylvania, Nationwide Children’s Hospital (NCH) and Genethon, a French charity. Also, several US charities, such as Sophia’s Cure, Cure SMA and Miracle for Madison, raised millions of dollars to advance the research.

The NIH RePORTer database lists nearly a half billion in grants, when the search term “Spinal Muscular Atrophy” is used, and every key U.S based researcher has been the principal investigator for millions dollars in NIH grants.

  • Projects mentioning “spinal muscular atrophy”: Projects: 1315, Funding: $442,817,030, Subprojects: 130, funding: $30,083,646
  • Brian Kaspar, NIH grants: Projects: 17, Funding: $6,371.705
  • James M. Wilson NIH grants: Projects: 103, Funding: $94,955,074; Subprojects: 85, Funding: $17,668,168
  • Jerry Mendell NIH grants: Projects: 29, Funding: $21,520,577, Subprojects: 76, Funding: Projects: $6,489,005

Below are quotes from and links to several press releases from non-profit patient and research organizations, highlighting their role in the development of Zolgensma.

The role of charities in funding research related to SMA in general and Zolgensma in particular has been quite important. It is moving to read the fundraising appeals from charities like Sophia’s cure, and to see how extensively Brian Kaspar and others have relied upon the parents and extended families of children who have SMA. The reporting on the rollout of the new treatment has not done justice to the role that non-profit institutions have played in the development of Zolgensma (a common omission for innovative treatments).

The FDA could require companies seeking to obtain marketing approval for novel treatments to provide an accounting of the role of charities and government agencies, in the U.S. and in foreign countries, that have subsidized relevant research. Indeed, such an obligation would give effect to one of the provisions in the new World Health Organization resolution on transparency, regarding the transparency of R&D subsidies.

Treatsma UK

    The work on gene therapy for SMA has a long history. Everything started in the early 2000s in Paris where Dr Martine Barkats, funded by the French patient and research organisation AFM Telethon, successfully treated SMA mice with an AAV9 viral vector. Soon her success was replicated by Dr Brian Kaspar in the US. Understanding the significance of the discovery, Dr Kaspar went on to study the virus and soon was able to treat SMA mice and even SMA pigs that he developed for the purpose. Seeing his successes and the promise the treatment had for people with SMA, the US SMA community offered to fund his work.


    Created by the AFM-Telethon, the French Muscular Dystrophy Association (AFM), Genethon, located in Evry, France, is a non-profit R&D organization dedicated to the development of biotherapies for orphan genetic diseases, from the research to clinical validation. Genethon is specialized in the discovery and development of gene therapy drugs and has multiple ongoing programs at clinical, preclinical and research stage for neuromuscular, blood, immune system, and liver diseases.

Press Release. May 27, 2019. Genethon welcomes the first FDA-approved gene therapy for a neuromuscular disease and emphasizes its decisive role in this historic step, Genethon.

    Genethon, the AFM-Telethon laboratory, played a decisive role in the design of both the product and the route of administration of this first gene therapy for a neuromuscular disease, thanks to the pioneering work lead by Martine Barkats and her team. In fact, the French researcher demonstrated that a recombinant AAV9 vector made it possible to cross the blood-brain barrier and thus reaching motor neurons, whose dysfunction is responsible for spinal muscular atrophy, and that such a vector carrying the smn1 gene extended the life span of mouse models of spinal muscular atrophy. These discoveries had been the subject of patents filed as early as 2007 and scientific publications in 2009 in Molecular Therapy, and in 2011 in Human Gene Therapy. In 2018, Genethon granted AveXis a license to patents in the U.S., Europe and Japan, for the AAV9 SMN product and in vivo gene therapy delivery of AAV9 vector into the CNS using intrathecal or intravenous routes of administration for the treatment of SMA.

March 13, 2018. Press Release: AveXis Enters into Licensing Agreement with Genethon. Includes exclusive worldwide rights to AAV9-SMN product and route of administration

    CHICAGO and ÉVRY, France , March 13, 2018 (GLOBE NEWSWIRE) — AveXis, Inc. (NASDAQ:AVXS) and Genethon today announced they have entered into an exclusive, worldwide license agreement for in vivo gene therapy delivery of AAV9 vector into the central nervous system (CNS) for the treatment of spinal muscular atrophy (SMA).
    “Adding to our robust intellectual property estate, this agreement further strengthens our position by providing freedom to operate when using intravenous or intrathecal routes of administration to deliver the AAV9 vector into the CNS for the treatment of SMA,” said Sean Nolan, President and Chief Executive Officer of AveXis. “With our proprietary gene therapy, AVXS-101, currently being evaluated in patients with SMA in ongoing clinical trials in the U.S., and soon in Europe, we are pleased to have this exclusive worldwide agreement in place.”
    Under the terms of the agreement, Genethon granted AveXis a license to patents in the U.S., Europe and Japan, for the AAV9 SMN product and in vivo gene therapy delivery of AAV9 vector into the CNS using intrathecal or intravenous routes of administration for the treatment of SMA. . . .

Sophia’s Cure

Press Release. September 8, 2010. Spinal muscular atrophy research team receives Pepsi Refresh funds from Sophia’s Cure Foundation, Sophia’s Cure Foundation.

    Nationwide Children’s Hospital receives $250,000 grant for SMA research
    Brian Kaspar, PhD, principal investigator in the Center for Gene Therapy at The Research Institute at Nationwide Children’s Hospital, along with a team of Spinal Muscular Atrophy (SMA) researchers and clinicians, recently received a $250,000 grant for SMA research and clinic development from Sophia’s Cure Foundation via the Pepsi Refresh Project.

March 9, 2011. The Path Forward

    We cannot fund this alone……….we need YOU to help turn this into a reality. The AAV9 Gene Therapy program is in dire need of $1,000,000 in funding and right now there are no commitments to see this funded. We cannot turn our backs on these kids now. Similar programs have received $2,000,000 to $15,000,000 in funding from the community. To date the AAV9 at Nationwide has seen a combined total of $600,000 and we need to raise $1,000,000 more to move this into clinical trials in a year. That timeline and these required studies are the guidelines that have been set forth by a Pre Pre Ind conversation with the FDA.
    This is going to require a monumental effort by all of us to see this through! We cannot wait to see who may help in the future………and $1,000,000 in a year will require action now. This can become a reality but we must work together. We need 200 commitments of $5,000. Are you willing to commit to raising $5,000 by March 9, 2012? If you can raise $10,000 that is great ………that would take care of 2 commitments. In order to move forward with this program we need to know who is on board. Whether you are an individual, a family, a non-profit, a company you can get involved. Are you willing to take a $5,000 chance on this program?

August 26, 2012. Because Research Matters

    We are so excited that SCF has wrapped up such a long and focused commitment to advance AAV9 towards a clinical trial. What was necessary to advance Gene Therapy towards a human clinical trial was sustained support at extremely high levels. We most certainly take a different approach to SMA research and we are absolutely ecstatic that we have pushed a very promising research program along at a pace that has never been accomplished before in SMA for a novel therapy. We are also very proud to say that the translational team did not shy away from the most severe phenotype. Instead this team decided to try to start in the most aggressive form of the disease. There are many questions that must be resolved and the only way to answer these questions is by attacking the most difficult problems first. It was amazing to watch the initial doubt, turn into support over the years and eventually that support turned into excitement. Our programs have raised an eye opening $2.3 Million dollars for Kaspar Labs at Nationwide Children’s Hospital. The very generous support SCF received from our donors enabled us to leverage their donations and multiply those numbers into great sums. Quite frankly without that multi-million dollar investment, Dr Brian Kaspar’s Gene Therapy Program would be many years away from where this program is today. Years in SMA are in fact lifetimes. When programs take 10 -15 years to reach a clinical trial in SMA, that means 5 – 7 generations of SMA children will pass before ever trying a single therapy on the patient population. Our goal in an aggressive disease such as SMA was to take the 15 year time frame for potential drug therapies and shorten that as much as possible. We are ecstatic that this program is marching towards an IND application in just 3 years. So Thank You to our donors!

Sept. 20, 2013. letter from Nationwide Children’s Hospital: A Special Statement for our Supporters and Advocates of SMA Research

    Generous funding for this trial and the FDA studies required for the investigational drug application has been provided by The Sophia’s Cure Foundation.
    An additional program also using the AAV9-delivered SMN gene will examine a different route of delivery by injecting the virus into the cerebro spinal fluid.This program will also move toward clinical testing thanks to substantial support from the Families of SMA and the National Institute of Neurological Disease and Stroke (NINDS).
    Dr. Kaspar notes, “We are extremely excited to be advancing two delivery routes to SMA patients and will continue to tirelessly move these programs in a rapid and safe manner. We thank everyone for their support in our efforts to develop treatments for this disease.”

Cure SMA

Press Release. May 24, 2019. AveXis Receives FDA Approval of Zolgensma, a Gene Therapy, for Spinal Muscular Atrophy for Patients Under Two Years of Age, Cure SMA.

    Beginning in 2010, Cure SMA made a series of grants to Nationwide Children’s Hospital to study gene therapy, also called gene transfer. Spinal muscular atrophy (SMA) is caused by a mutation in the survival motor neuron 1 gene (SMN1). Because of this mutation, the individual does not produce enough survival motor neuron (SMN) protein.

Therapeutic Approaches

    Cure SMA Funding for Gene TransferIn 2010, Cure SMA made a $100,000 drug discovery grant to Dr. Brian Kaspar for SMA gene therapy development. Dr. Kaspar’s project tested Adeno-associated virus type 9 (AAV9), to see if that virus could cross the blood-brain barrier at different ages, and to investigate how quickly we need to target motor neurons in children with SMA in order for the treatment to be effective.
    Ongoing Research and Testing
    In 2012 and 2015, we awarded Dr. Kaspar a total of $745,000 to support his work on gene therapy delivered specifically to the central nervous system (CNS-delivered gene therapy). With this additional grant, Dr. Kaspar was able to test for an optimum dosage in both mice and non-human primates.
    Taking Gene Therapy Toward Clinical Trials
    In 2013, Dr. Kaspar received a nearly $4 million government grant from the National Institute of Neurological Disorders and Stroke (NINDS), using the early data generated with our funding.The grant supports additional work needed to move CNS-delivered gene therapy toward clinical trials through submission of an Investigational New Drug (IND) application to the FDA. This project represents an important collaboration between researcher, government, and Cure SMA.

Miracle for Madison

    The Miracle For Madison fund sits within The Ohio State University Foundation acct. # 301554. Miracle For Madison & Friends is a grassroots, 100% volunteer driven group of individuals consisting of family and friends. All money raised goes directly to support research and clinic services for SMA at OSU. All expenses, advocacy, education and family support is donated by Madison’s family and friends.
    Miracle for Madison is a fund set up to:
  • Raise needed dollars for OSU researchers to find a cure.
  • Support the SMA clinic at Nationwide Children’s Hospital and coordinate medical services for SMA patients.
  • Educate the medical community about the most up to date standard of care and treatment.
  • Provide support to SMA families.

University of Pennsylvania

Press Release. May 24, 2019. Newly Approved Spinal Muscle Atrophy Treatment Zolgensma is Based on Delivery System Discovered by Penn Gene Therapy Pioneer, Penn Medicine.

    Today, Wilson and his team are celebrating a major milestone in the field: approval by the U.S. Food and Drug Administration (FDA) of a gene therapy known as Zolgensma for SMA. The therapy is based on a delivery vehicle that his team discovered and developed over the past decade as part of a wide-ranging portfolio of research to advance gene therapy.
    In 2009, REGENXBIO, a clinical-stage biotechnology firm, secured exclusive rights to key intellectual property covering novel recombinant adeno-associated viral vectors discovered at Penn in the Wilson lab. Today, over 75 disease programs across more than 25 companies use the AAV-based platform. AAV9 was the vector used in the Phase I SMA clinical trial at Nationwide Children’s Hospital for the approved therapy Zolgensma. REGENXBIO licensed the vector to AveXis in 2014, and AveXis was subsequently acquired by Novartis in 2018.

Nationwide Children’s Hospital (US based children’s hospital)

Press Release. October 18, 2013. AveXis- BioLife Licenses Spinal Muscular Atrophy (SMA) Patent Portfolio from Nationwide Childrens Hospital and The Ohio State University.

    BioLife, a synthetic biology platform company soon to be renamed AveXis, has been granted exclusive rights to the spinal muscular atrophy gene therapy program developed at The Research Institute at Nationwide Children’s Hospital and The Ohio State University in Columbus, Ohio.
    The license enables the company’s focus on the treatment of children with spinal muscular atrophy (SMA), a motor neuron disease which is the leading genetic killer of children under the age of two. SMA is the second most common pediatric autosomal recessive disorder with an incidence of one in 6,000 live births. SMA is known to be caused by lack of expression of survival motor neuron (SMN) protein due to a genetic loss of the SMN1 gene.
    The licensed technology encompasses the unique ability to deliver the SMN gene across the blood brain barrier or through the cerebrospinal fluid to effectively target motor neurons throughout the brain and spinal cord. In pre-clinical efficacy studies in the severe rodent model of SMA, a one-time treatment of the gene therapeutic improved survival from the average lifespan of 14 days to over 400 days. Additionally, the one-time treatment was safe and well tolerated.
    AveXis-BioLife has secured the key intellectual property developed at The Center for Gene Therapy at The Research Institute at Nationwide Children’s Hospital and The Ohio State University. The findings have been led by Brian K. Kaspar, Ph.D. a Principal Investigator at The Research Institute at Nationwide Children’s Hospital and Associate Professor at The Ohio State University College of Medicine along with collaborator Arthur Burghes, Ph.D. Professor at The Ohio State University. Dr Kaspar stated, “We are thrilled to partner our SMA program with AveXis-BioLife to rapidly move our findings to SMA patients and look forward to initiating human clinical trials in early 2014.”
    A clinical trial has been planned with Jerry R. Mendell, M.D., director of the Center for Gene Therapy andPrincipal Investigator in The Research Institute at Nationwide Children’s Hospital and the team recently received approval for an investigational new drug application in September.

Press Release. May 24, 2019. FDA Approves First Gene Therapy Treatment for SMA Developed at the Abigail Wexner Research Institute at Nationwide Children’s Hospital, Nationwide Children’s Hospital.

    The preclinical work leading to the FDA approval of Zolgensma was conducted by researchers from Nationwide Children’s and The Ohio State University College of Medicine. In a key milestone toward advancing the research, Brian Kaspar, PhD, during his tenure with Nationwide Children’s, discovered that the AAV9 vector was capable of crossing the blood brain barrier when injected into the vascular system to deliver genes directly to motor neurons. Dr. Kaspar is currently the Chief Scientific Officer at AveXis, Inc.