Glycogen Storage Disease Research Study is Enrolling

Alexa Bream, a genetic counseling student at University of Texas Health Science Center at Houston (UTHealth), is conducting a survey to examine the relationship between metabolic control, body image, and quality of life in individuals with glycogen storage disease (GSD) type 1a. The survey is available for parents of children with GSD 1a, as well as adults who have a diagnosis of GSD 1a. No personally-identifiable information will be collected and all responses will be confidential. For more information please contact Alexa Bream.

MPS Society in the UK has Appointed Bob Stevens as its New CEO

The Board of Trustees of the Society for Mucopolysaccharide Diseases in the United Kingdom (the “MPS Society”) has appointed Bob Stevens as its new CEO. Mr. Stevens was already working with Christine Lavery prior to her unexpected death, on the task of becoming prepared to lead the MPS Society after her retirement. Additionally, he has been a Trustee of The MPS Society for over 10 years. Mr. Stevens has two sons who have MPS II.

In making this appointment, Paul Moody, Chairman of the Board of Trustees of the MPS Society, wrote: “The Board of Trustees have now acted decisively and quickly in implementing not only what we believe were Christine’s wishes, but also the unanimous wishes of the board of trustees.” Mr. Stevens is also the CEO of the Society’s “MPS Commercial,” its unit that works to help the pharmaceutical industry successfully perform clinical trials for the MPS diseases. MPS Commercial is a wholly-owned, not-for-profit subsidiary of the Society, whose social objectives are to invest any profits into the MPS community for the purposes of education, enhancing needs-led advocacy support, quality-of-life research and scientific research.

Christine Lavery, Chief Executive of the MPS Society in the UK, has Died

Mrs. Christine Lavery MBE, a founder and the Chief Executive of the Society for Mucopolysaccharide Diseases (MPS Society) in the UK, died on Tuesday, December 19, 2017, following a brief illness. The MPS Society stated, “Christine has tirelessly championed the MPS Society from its very conception in the early 1980s up until her untimely death. She was a formidable lady who cared passionately for every MPS Society member, past and present. Her efforts saw her work with patients, families and professionals all over the world as she dedicated her life to improving the knowledge, advocacy support and clinical outlook for patients with MPS. We are all deeply saddened at the tragic loss of her life.” The MPS Society has announced the Christine Lavery Memorial Day at Childhood Wood, Sherwood Pines, Nottinghamshire, UK, on Saturday, June 30, 2018. To receive more details about this as they emerge, register for updates.

Mrs. Lavery was awarded an MBE for her services to metabolic diseases by HM Queen Elizabeth II in the New Year’s Honors List for 2002. At the 2006 International Symposium on Mucopolysaccharide and Related Diseases she received a ‘lifetime award’ from the International MPS Community. WORLDSymposium™ awarded Christine Lavery the 2017 Patient Advocate Leader (PAL) Award.

Mrs. Lavery was the mother of Simon Lavery, a child who had MPS II. There are some brief biographical highlights of Christine Lavery’s life at the Brains for Brain Foundation site, under the paragraph-heading “Christine Lavery Short Biography.” Prior to serving the lysosomal disease community, Mrs. Lavery volunteered for Save the Children and the International Year of the Child. That short biography reveals a lifetime of focused dedication to improving the lives of those with special needs. She is deeply missed throughout the world.

Ultragenyx Announces FDA Approval of MEPSEVII™ (Vestronidase Alfa), The First Therapy for Mucopolysaccharidosis VII

On Nov. 15, 2017, Ultragenyx Pharmaceutical Inc. announced that the U.S. Food and Drug Administration has approved MEPSEVII™ (vestronidase alfa), the first medicine approved for the treatment of children and adults with mucopolysaccharidosis VII (MPS VII, Sly syndrome). MEPSEVII™ is an enzyme replacement therapy designed to replace the deficient lysosomal enzyme beta-glucuronidase in MPS VII patients. The effect of MEPSEVII™ on the central nervous system manifestations of MPS VII has not been determined.

MEPSEVII™ was evaluated by the FDA with Priority Review, which is reserved for drugs that offer major advances in treatment or provide a treatment where no adequate therapy exists. Designation of a drug as “Priority” does not alter the scientific/medical standard for approval or the quality of evidence necessary. In Europe, the European Medicines Agency (EMA) is currently reviewing the Marketing Authorization Application (MAA) for vestronidase alfa, and an opinion from the Committee for Medicinal Products for Human Use (CHMP) is expected in the first half of 2018.

“I am thrilled beyond belief to see this treatment advance after more than 40 years of work and anticipation. Thanks to Ultragenyx for making it happen,” said William S. Sly, Chairman Emeritus, Department of Biochemistry at St. Louis University, who first identified and characterized MPS VII. “I hope that this treatment will follow the other successful examples of enzyme therapy for LSDs and help improve the lives of patients with this rare disease.” Former 2016-2017 Lysosomal Disease Network fellow Michael Flanagan, PhD, had the privilege of being partly mentored by Dr. Sly during his LDN fellowship at St. Louis University.

Experiment in Genome Editing Inside a Living Person Occurred on Monday, November 13, 2017

44-year-old Brian Madeux, who has MPS II (Hunter syndrome), was the first patient to undergo an experiment in genome editing inside a living person on Nov. 13, 2017 in Oakland, California using Sangamo Therapeutics, Inc.‘s zinc finger nuclease (ZFN) genome editing technology. The procedure was performed at UCSF Benioff Children’s Hospital Oakland. If successful, this genome editing will not repair Brian Madeux’s existing damage from MPS II, but he hopes it will end his need for weekly enzyme replacement therapy infusions.

This is a Phase 1/2 clinical trial (“the CHAMPIONS study”) evaluating SB-913, an investigational in vivo genome editing therapy. The CHAMPIONS study is an open-label clinical study designed to assess the safety, tolerability and preliminary efficacy of the SB-913 investigational genome editing therapy in up to nine adult males with MPS II. Other CHAMPIONS study sites include Minneapolis, Chapel Hill, Chicago and Philadelphia. Currently at these study sites, prospective study participants are being screened. In Minneapolis at the University of Minnesota, the Lysosomal Disease Network’s principal investigator Dr. Chester B. Whitley is conducting the CHAMPIONS study.

Two additional clinical trials are now underway in the United States to evaluate Sangamo’s in vivo genome editing therapeutics for hemophilia B and MPS I (Hurler or Hurler-Scheie syndrome). The Lysosomal Disease Network’s principal investigator Dr. Chester B. Whitley is also conducting the MPS I genome editing study at the University of Minnesota. Other sites in this MPS I study include Oakland, New York City and Cincinnati. All three trials use ZFNs designed to edit liver cells at the same location in the albumin gene, but they differ in delivering the corrective gene relevant to the respective disease. All three of Sangamo’s in vivo genome editing product candidates have received Fast Track and Orphan Drug designations from the U.S. Food and Drug Administration. Additionally, SB-318 for MPS I and SB-913 for MPS II have received Rare Pediatric Disease designations from the FDA.

LDN Fellow Named as Outstanding Mentor

Reena Kartha, PhD, a former LDN Fellow, is a Research Assistant Professor with the University of Minnesota College of Pharmacy’s Department of Experimental and Clinical Pharmacology, and a Principal Scientist for the College of Pharmacy’s Center for Orphan Drug Research. Her research focuses on the role of oxidative stress and inflammation in neurodegenerative conditions. Dr. Kartha also generously helps interview applicants for the University of Minnesota Center for Clinical and Translational Science Institute’s summer programs. Dr. Kartha has been named the 2017 CTSI Outstanding Junior Mentor.

Dr. Kartha receives her award for Outstanding 2017 Junior Mentor

Reena Kartha, PhD receives the Univ. of Minnesota’s CTSI 2017 Outstanding Junior Mentor award. Reena Kartha, PhD (right), and Anne Marie Weber-Main, co-director of CTSI’s mentoring program (left).

Comments from nominating mentees included: “Dr. Kartha is one of the most intelligent women I have ever had the honor of meeting and I am inspired by her internal strength, wisdom, confidence, and grace. She is someone I hope and aspire to become, and not just from a researcher perspective, but as a person.”

and

“What distinguishes Dr. Kartha from most other mentors is the relationships she develops with her mentees. The net result is a string of trainees who have grown substantially as researchers and, more importantly, and have developed a sense of curiosity and excitement about clinical science.”

The Lysosomal Disease Network congratulates Dr. Kartha, and is proud to have chosen her as one of its 2016-2017 Fellows. Dr. Kartha also is a graduate of the RDCRN’s Rare Disease Clinical Research Training Program. She will be presenting her research at the NORD Rare Diseases and Orphan Products Breakthrough Summit, October 16-17, 2017 in Washington, D.C.

NCATS Launches Online Toolkit for Patient-Focused Therapy Development

The NIH’s National Center for Advancing Translational Sciences (NCATS) has launched its new Toolkit for Patient-Focused Therapy Development which provides a vast collection of online resources that can help patient advocacy groups advance through the process of therapy development. The Toolkit includes resources that have been developed primarily for the rare diseases community to facilitate therapeutics R & D. Since early 2016, NCATS has worked with a diverse group of rare diseases community partners to conduct an extensive analysis of available tools. Their hard labor defined, characterized and organized resources in a centralized portal that can be helpful to all patient groups, regardless of how far along in the research and development process they may be.

The new toolkit includes, but is not limited to:

Getting Started that focuses on learning how investigational therapies are developed; why it is important for patients and their advocates to engage throughout the process; and how to build effective relationships with other stakeholders.

Discovery Tools that aid in community organization and the prioritization of activities during the early stages of development.

Preparing for Clinical Trials Tools focused on getting patient communities ready for clinical trials.

Clinical Trials and FDA Review Tools to help connect patients to clinical trials, and to take part in the complex FDA regulatory-review process.

After FDA Approval Tools to help formulate the plan for integrating a newly-approved therapy into clinical care.

Take the time to explore the deep layers of nested links and the information they’ll take you to. NCATS has certainly produced an extremely useful, high-quality tool! What this new tool needs now — is for thousands of members of the rare diseases community to USE IT!

2017 Million Dollar Bike Ride Pilot Grant Program

The University of Pennsylvania Orphan Disease Center’s 2017 Million Dollar Bike Ride Pilot Grant Program is now open! The Million Dollar Bike Ride (MDBR) Pilot Grant Program will provide a one-year grant to support research related to a rare disease represented in the 2017 Million Dollar Bike Ride. All individuals holding a faculty-level appointment at an academic institution, or a senior scientific position at a non-profit institution or foundation are eligible to respond to this RFA. Interested applicants must first submit a Letter of Interest (LOI), which is done by completing a brief online form, and uploading a 1‐page Pre‐Application. This LOI is due by Monday, September 18, 2017 by 8:00 p.m. EST. Full grant applications are accepted by invitation only after LOIs are approved.

The following lysosomal diseases were represented in the 2017 Million Dollar Bike Ride last May in Philadelphia, and their available grants are detailed:

Mucolipidosis Type IV (ML4): One $71,939 pilot grant available. This grant is offered to investigators conducting research on all aspects of ML4 disease, including disease pathogenesis and clinical studies. Preference will be given to those research projects developing new therapies for ML4, and translational research projects that improve our understanding of the disease state and pathogenesis, such as identifying biomarkers or functional outcome measures to assess therapeutic impact. This grant is made possible by the intrepid riders of Together4Ido, TeamCureML4, Climb4Carin, Pedal4Paul, Danny4theGirls, and MayaanHikes4Meira.

Mucopolysaccharidoses (MPS): Two $59,449 pilot grants are available. Applications directed to treating the central nervous system manifestations or enzyme replacement therapy antibody responses are sought. These two grants are made possible by Team MPS, the National MPS Society, and The Ryan Foundation.

Niemann Pick Type C (NPC): Two $49,645 pilot grants are available. Consideration will be given to research projects developing new therapies for NPC, as well as those designed to complement therapies presently in the pipeline. Consideration will also be given to gene therapy proposals; studies focused on problems, including psychiatric issues, impacting quality of life through the lifespan of the patient population; and projects that improve our understanding of the biology, pathogenesis and disease state and that have a direct impact on translation of new treatments to patients. These two grants are made possible by Team NPC, the Andrew Coppola Foundation, Jammin’ for JP, Chase the Cure and iPedal4Chad.

Tay-Sachs, Sandhoff, GM-1, or Canavan Disease: One $42,419 pilot grant is available focusing on forms of Tay-Sachs, Sandhoff, GM-1, or Canavan disease. Proposals are solicited for innovative research projects that involve basic research, translational studies or clinical studies relevant to these diseases. Projects may be focused on (1) pre-clinical and clinical research needs, such as clinical outcome measures, registries, animal models, or biomarkers; or (2) technology approaches such as stem cells, molecular chaperones, substrate inhibitors, small molecule drug screening, gene therapy, or novel drug delivery to the brain. This grant is made possible by Team NTSAD and the National Tay-Sachs & Allied Diseases Association.

Questions regarding the scientific content of potential research projects can be directed to Monique Molloy; administrative queries should be sent to Samantha Charleston at the University of Pennsylvania’s Orphan Disease Center.

More on Newborn Screening for Lysosomal Diseases

Screening is Critical for Improved Outcomes!

Following-up on our previous post about the recent achievement in newborn screening for two lysosomal diseases in the state of Washington, the Association of Public Health Laboratories (“APHL”) has an excellent brief article by Michelle Forman, APHL’s senior specialist for media, posted on their blog on March 1, 2016, which provides both facts and insights about newborn screening for lysosomal diseases. Have you been wondering why getting the lysosomal diseases included in all 50 states’ newborn screening programs is taking so long and is requiring so much effort? Read Michelle’s cogent post, and you’ll know exactly why!

State of Washington Makes Progress in Newborn Screening for MPS I and Pompe Disease

Testing Those Newborn Blood Spots

On August 9, 2017 the Washington State Board of Health unanimously passed the addition of Pompe disease and mucopolysaccharidosis type I (MPS I) to their state’s newborn screening panel. The Board of Health is the policy body charged with making recommendations to the State of Washington regarding newborn screening. Over the summer the Board convened a technical advisory committee of parents, genetic experts, ethicists and other experts that met twice to consider the data surrounding these two additions, both of which had already been recommended as part of the federal Recommended Uniform Screening Panel. Washington has its own review criteria: available screening technology, diagnostic testing and treatment available, prevention potential and medical rationale, public health rationale, and cost benefit/cost effectiveness. The Board of Health reviewed the recommendations of the Advisory Committee and, as Dr. Thomas Pendergrass, Board Vice-Chair commented when making the motion to add Pompe disease, “This is impacting families and kids. It is something we can do something about. It is something that if we delay doing it we’ve lost he benefit of the short term.”

The materials presented can be downloaded from the Washington State Board of Health by scrolling to Item 09. Also, Item 07 on that web page contains some additional pertinent materials used by the Board in reaching its decision.

The Lysosomal Disease Network would like to thank all who participated on the Washington Board of Health technical advisory committee, the Board of Health and its staff, as well as those who testified at the two Board hearings where this was considered. In particular, the LDN would like to thank the parents of patients with MPS I and Pompe disease who testified about their experiences to the technical advisory committee and the Board of Health. Their stories vividly conveyed to policymakers the benefits of newborn screening. The testimony of Dr. Klane and Amy White, the parents of Susannah White, a child who died from MPS I, summed up the importance of newborn screening: “It is my belief, and that of most families unfortunate enough to have lived through our experience, that while not a perfect answer, newborn screening can reduce this variability and improve patient care. This is not to mention potentially alleviating months to years of uncertainty and anxiety experienced by families stuck in the diagnostic odyssey. It is my firm belief, as well as that of my peers in the rare disease community, that newborn screening is a critical and necessary step forward in the care of our children and families facing MPS and other rare diseases.”

Now, additional steps must be accomplished prior to being able to screen newborns for MPS I and Pompe disease. The Governor of Washington must recommend, and the Washington Legislature must appropriate, monies to implement the screenings in the 2018 legislative session. If this is successful, it will be followed by a rulemaking process through the Washington Department of Health. If all goes well, MPS I and Pompe disease could be added to newborn screening as early as Fall 2018.