Ongoing Sanfilippo Syndrome Type A (MPS IIIA) Gene Therapy Clinical Trial Enrolling Patients

Abeona Therapeutics, Inc. is enrolling patients in a Phase I/II non-randomized, open-label clinical trial studying a one-time gene therapy for Sanfilippo syndrome type A (MPS IIIA). They have entitled this study ‘The Transpher A Study.’ Caregivers interested in enrolling their children can visit AbeonaTrials.com to take an eligibility survey and learn more about the study. Additional details can be found at ClinicalTrials.gov under study number NCT02716246 or by contacting infotrials@nullabeonatherapeutics.com.

Funded Rare Disease Clinical Research Training Program

“Rare Opportunity
for Young Researchers”

The Rare Diseases Clinical Research Network (RDCRN) annually offers early-career rare disease researchers this excellent training and networking opportunity. This is available to researchers associated with one of the RDCRN’s research consortia. (The Lysosomal Disease Network is one such RDCRN consortium.) The Rare Diseases Training Program is recruiting for the 2019 – 2020 academic year. More information about the Rare Diseases Training Program, as well as the form to complete and submit as part of your application, are available by clicking on the download link on this web page (scroll down). The Rare Disease Clinical Research Training Program accepts applications and sends-out acceptances on a rolling basis.

This academic-year-long course consists of both in-person and remote sessions providing the tools and mentoring needed for a successful career in rare diseases clinical research. Topics include: statistics in small populations, interactions with industry and pharmaceutical companies, successful grant writing, working with patient and family advocates and groups, research career design and planning, and successful publishing in the field of rare diseases.

Participation requires a 10% time-commitment from the applicant’s program chair or department chair for the applicant’s dedicated, focused research time. In addition, the program requires: two 2-day trips to the Washington, D.C. area; two 1-hour webinars per month; completion of a mentored research project with culmination in a poster presentation at the Fall 2020 RDCRN meeting in the Washington, D.C. area; and about 4 hours of projects/reading per month for preparation. Certificates will be awarded to participants completing at least 75% of the course content at or above acceptable levels. The first 2-day trip to the Washington, D.C. area will occur October 21-22, 2019.

Twenty competitive participants will be awarded a “funded” position. This funding will provide $1,000/year reimbursement towards attending the two 2-day trips to the Washington, D.C. area. Applicants can apply for the funded program (the “travel group”), while also indicating that they wish to be considered for the unfunded program if not chosen for funding. Up to twelve additional unfunded positions are available to excellent applicants this year.

Applicants are requested to submit the following: the completed downloadable application form (scroll down); their CV; and a letter of commitment from their supervisor supporting their participation in this Training Program, as well as offering to support any costs that exceed the reimbursed costs (if any) of participation in this Training Program.

Sanfilippo Syndrome type A (MPS IIIA) Gene Therapy Trial is Enrolling Participants

Lysogene is excited to announce the launch of its phase 2-3, single-arm trial to assess the efficacy of direct-to-CNS delivery of LYS-SAF302 in improving or stabilizing the neurodevelopmental status of MPS IIIA patients.

The search is on for MPS IIIA patients who fit the eligibility criteria for this trial, which is entitled “Multi-Center Study of AAVrh10-h.SGSH Gene Therapy in Patients with MPS IIIA (AAVance).” Details are available on ClinicalTrials.gov under its study number NCT03612869, or contact: patientadvocacy@nulllysogene.com.

New Conclusions About
Fabry Patients and
White Matter Lesions

A research team led by Simon Körver of Amsterdam Academic Medical Center, University of Amsterdam’s Department of Endocrinology and Metabolism, has conducted and published in-depth analyses of forty-six published research studies that included the results of brain MRI investigations in 1,276 Fabry disease patients. These research studies were identified using Pubmed, EMBASE and CINAHL databases dated from inception to February 15, 2018. The researchers assessed the prevalence, severity, location and course of white matter lesions in these Fabry disease patients. Prevalence and severity were assessed for all patients combined, as well as divided by gender. They systematically reviewed the studies’ evidence on the relation between white matter lesions, disease characteristics, and clinical parameters.

One of their findings is that men and women showed comparable prevalence and severity of white matter lesions. Males, however, were significantly younger at time of white matter lesion assessment. Follow-up brain MRI in both men and women 38 months later revealed white matter lesion progression in 24.6% of patients, with and without enzyme replacement therapy, but at an earlier age in men.

Among their conclusions is that a significant group of Fabry disease patients has substantial white matter lesions, and male patients develop white matter lesions earlier compared to female patients. They suggested that future studies should focus on longitudinal brain MRI follow-up using state-of-the-art imaging techniques. They also suggested a clinical focus on the consequences of white matter lesions in Fabry disease patients. The article dives deeply into the details of their important findings.

Collaborations Pharmaceuticals Inc Receives Funding from NINDS to Partner with Washington University on Batten Disease

National Institute of Neurological Disorders and Stroke (NINDS) at NIH has awarded $229,560 to Collaborations Pharmaceuticals Inc of Raleigh, NC to initiate a project at Washington University (St. Louis, MO) aimed at developing an enzyme replacement therapy to treat infantile Batten disease, also known as CLN1. The company will partner with Batten disease researcher Jonathan Cooper, PhD, Professor of Pediatrics at Washington University School of Medicine.

This treatment approach, originally funded by Taylor’s Tale (an LDN-affiliated patient advocacy group) and NINDS, began in the lab of Sandra Hofmann, MD, PhD, at the University of Texas Southwestern (Dallas, TX). Supported by these funds, Dr. Hofmann and her research team performed extensive development of the protein as well as pre-clinical assessment. Taylor’s Tale, a 501(c)3 public charity based in Charlotte, NC, funded Dr. Hofmann’s work beginning in 2007.

Moving forward, Collaborations Pharmaceuticals Inc will further develop the PPT1 enzyme, setting the stage for future clinical studies of this potential treatment for CLN1. In 2017 Collaborations Pharmaceuticals Inc received Orphan Drug Designation from the FDA for this PPT1 enzyme.

Collaborations Pharmaceuticals Inc is led by CEO Sean Ekins, PhD, who is also the President, CEO, and co-founder of Phoenix Nest, Inc.

Batten Disease Support & Research Association Launches Two New Pilot Programs

The Batten Disease Support & Research Association (BDSRA) has launched two new pilot programs: the Batten Family Help Fund and the Emerging Research Conference Travel Award. The Batten Family Help Fund is a small-grant program of up to $750 to be used for family emergencies helping children, young people or adults (and their immediate families or those who care for them) living with Batten disease in the United States. The financial support of caring donors, including the BDSRA 2018 Family Conference attendees in Nashville, made it possible for the BDSRA to create this new program. Use this online form to apply for this emergency grant.

The Emerging Research Conference Travel Award seeks to educate and motivate researchers new to the Batten disease field to pursue projects in Batten disease by helping to cover the costs of attending the International Conference on Neuronal Ceroid Lipofuscinoses in London, UK, September 12-16, 2018. At their annual family conference in Nashville which convened in July 2018, the BDSRA chose four recipients of this award.

10th Annual Rare Disease Scientific Workshop Conceptualizing a Rare Disease Center of Excellence at the FDA

The EveryLife Foundation convened its 10th annual Rare Disease Scientific Workshop, titled “Conceptualizing a Rare Disease Center of Excellence at the FDA,” in Washington, DC on Sept. 13, 2018. The goal of the workshop was to gather key thought-leaders from industry, the Food and Drug Administration (FDA), and patient organizations to discuss potential models, best practices and the pathway forward.

Senior-level officials from the FDA and National Institutes of Health (NIH) presented, along with representatives from industry and patient advocacy organizations. The video of this event, arranged in discrete, consecutive-speaker-order, is available online now.

The Growing Promise of
Gene Therapy Approaches
to Rare Diseases

UPDATE after this event: The videocast recordings of “The Growing Promise of Gene Therapy Approaches to Rare Diseases” workshop, held August 20–21, 2018 at NIH, are now available from the NIH Videocast Archives. To find the two separate recordings, please notice that below that web page’s title “Most Recent VideoCasts” is a small calendar-icon located to the right of the array of page numbers. Click on that calendar-icon and select either August 20 or 21, 2018. The 2-day event’s videocasts are listed under their respective calendar dates.

On August 20-21, 2018 in Bethesda, Maryland, the National Center for Advancing Translational Sciences (NCATS) and the Food and Drug Administration’s Center for Biologics Evaluation and Research co-sponsored a workshop entitled “The Growing Promise of Gene Therapy Approaches to Rare Diseases.” The workshop reviewed the state of current gene therapy approaches; identified challenges and strategies to overcome those challenges; and discussed how to collaboratively scale and accelerate gene therapy development to benefit patients with rare diseases for which there are yet no effective treatments. Lysosomal Disease Network’s Principal Investigator, Dr. Chester B. Whitley, was among the speakers on a panel, and spoke about gene therapy for lysosomal diseases. This joint meeting facilitated discussion among stakeholders including NIH and FDA staff, academics, researchers, biotech- and pharma-industry, and patient group representatives, on overcoming bottlenecks in the development of gene-based therapies. The workshop convened at National Institutes of Health (Main Campus), NIH Clinical Center, in Bethesda, Maryland. There was no admission fee to attend.

ArmaGen, Inc. Announces
FDA Granting of
Orphan Drug Designation
to AGT-184

On August 2, 2018, ArmaGen, Inc., a biopharmaceutical company located in Calabasas, California, announced that the U.S. Food and Drug Administration’s Office of Orphan Products Development has granted Orphan Drug Designation to its investigational agent AGT-184 for the treatment of lysosomal disease mucopolysaccharidosis type IIIA (also known as MPS IIIA, or Sanfilippo syndrome type A). AGT-184 is an investigational enzyme replacement therapy for the treatment of the cognitive effects of MPS IIIA. The missing or diminished enzyme needing therapeutic replacement is N-sulfoglucosamine sulfohydrolase (“SGSH”).

AGT-184 is an immunoglobulin G (“IgG”)-SGSH fusion-protein, where the IgG portion is a human anti-insulin receptor monoclonal antibody. The insulin receptor antibody domain triggers transport of the AGT-184 fusion-protein across the blood brain barrier, by binding to endogenous insulin receptors present on the blood brain barrier. Normally, the blood brain barrier blocks large molecules such as enzymes from entering the brain. In effect, this is a Trojan Horse approach to successfully delivering the therapeutic agent to the brain. ArmaGen, Inc. is currently conducting Investigational New Drug (“IND”) application-enabling activities (manufacturing, toxicology studies), with the goal of filing an IND application with the U.S. Food and Drug Administration in late 2019.

The FDA grants Orphan Drug Designation to drugs intended to treat a rare disease or condition affecting fewer than 200,000 people in the U.S. This designation confers special financial incentives to the drug developer, including tax credits on clinical development costs and prescription drug user-fee waivers, and it may confer the right to seven years of market exclusivity in the U.S. upon FDA approval of the orphan drug.

2018 Rare Disease Day at NIH
Event Video is Now Available

On March 1, 2018 “Rare Disease Day at NIH” convened at the National Institutes of Health in Bethesda, Maryland. Rare Disease Day takes place worldwide, typically on or near the last day of February each year, to raise awareness among policymakers and the public about rare diseases and their impact on patients’ lives. The theme for Rare Disease Day 2018 was research, and the slogan was “Patients are not only subjects but also proactive actors in research.” Free and open to the public, the all-day event at NIH was sponsored by the National Center for Advancing Translational Sciences (NCATS) and the NIH Clinical Center. It featured podium presentations, posters, exhibits, an art show, and tours of the NIH Clinical Center. Among the presenters was Chester B. Whitley, PhD, MD, the Principal Investigator of the Lysosomal Disease Network. The presentations were live-streamed on March 1, and are now available as online video. Dr. Whitley’s portion of the presentations begins at 1 hour 12 minutes into the video. The entire event video provides a valuable opportunity to increase one’s knowledge of rare diseases and their impact upon individuals and their communities. It also provides insights into the current state-of-the-art in rare diseases research and treatment.

Lysosomal Disease Network Request for Proposals (RFP)

The Lysosomal Disease Network (LDN) issued a Request for Proposals (RFP) for studies aiming to participate in the competitive re-application to the National Institutes of Health “Rare Diseases Clinical Research Network” program. Details are provided in this document.

A Letter of Intent (LOI), with outline (a brief outline addressing proposed elements of the standard NIH PHS 398 form), was due at the LDN office on January 1, 2018. Following a brief constructive response from the LDN to their LOI and brief outline, completed outlines of applications were due by January 30, 2018. On February 9, 2018, a “Pitch Meeting” occurred at the LDN Expert Advisory Committee gathering at the Manchester Grand Hyatt San Diego Hotel, San Diego, California, USA. At that time each applicant delivered an oral presentation of their proposal to the LDN Expert Advisory Committee.

Lysosomal Disease Network’s
Council of Patient Advocates 2018 Workshop

The Lysosomal Disease Network’s Council of Patient Advocates (“COPA”) convened their 2018 Workshop on Monday morning, February 5, 2018 at 9:00 a.m. The COPA Workshop was held at the Manchester Grand Hyatt San Diego Hotel in San Diego, California, which was also the venue for WORLDSymposium™ 2018. The annual COPA Workshop is open to patients, their family members/caregivers, and patient advocacy group representatives who desire an active role in partnering with the LDN to provide input to patient-focused studies and clinical trials. There is no cost to attend this meeting. Each January, information about the upcoming COPA Workshop (and how to RSVP for it) will be posted here on the LDN homepage.

The Lysosomal Disease Network Awards LDN Fellow for 2017-2018

The Lysosomal Disease Network (LDN) is pleased to announce that it has selected Laura Adang, MD, PhD of The Children’s Hospital of Philadelphia for a fellowship that provides $50,000 for lysosomal disease clinical research. Her research project is entitled “Metachromatic leukodystrophy: characterization of genetic mutations, age of onset, and clinical subtypes.” Dr. Adang’s mentor for this project is Dr. Adeline Vanderver, also with The Children’s Hospital of Philadelphia. Dr. Adang’s fellowship period is August 1, 2017 – July 31, 2018. Click here for more information about the LDN’s fellowship opportunities.

Laura Adang, MD, PhD

Laura Adang, MD, PhD

The project is a multi-center retrospective natural history study to characterize the disease course in patients affected by metachromatic leukodystrophy (MLD). It will use statistical modeling to analyze collected clinical data to classify distinct subpopulations within the heterogeneous MLD population. Ultimately, it will evaluate the correlation and distinctions between the subpopulations with respect to genetic, radiographic, and ancillary clinical phenotypes, including gallbladder and renal involvement. Dr. Adang said the project goals include “validating or possibly redefining the clinical subtypes of metachromatic leukodystrophy. This can be used to design future studies and therapeutic trials. Importantly, with a better understanding of metachromatic leukodystrophy, we will be able to offer our families better anticipatory guidance, establish appropriate standards of care, and design better future therapeutic trials.”

Dr. Marc Patterson, Director, Education Core of the Lysosomal Disease Network, said “The Lysosomal Disease Network looks forward to a very productive research project, and wishes Dr. Adang the greatest success in achieving the goals of this research project, with a peer-reviewed publication summarizing the findings. Dr. Adang will also participate in the NIH-funded RDCRN Rare Disease Clinical Research Training Program, which is also open to new clinical investigators.”

Join the Contact Registry

You (or your child) are invited to participate in the nationwide Contact Registry for lysosomal disease patients. The Rare Diseases Clinical Research Network (RDCRN) offers this patient Contact Registry. This is a method by which patients with lysosomal diseases can register themselves online with the RDCRN in order to be contacted in the future about clinical research opportunities and updates on the progress of the research projects. The contact registry is anonymous and free of charge.

The Lysosomal Disease Network encourages lysosomal disease patients or their families to register. Because of the rarity of lysosomal diseases, the Contact Registry plays an important role in estimating the incidence and prevalence of these conditions, and in keeping interested persons informed about available clinical research for treatment and cure of lysosomal diseases.

4th Conference on Clinical Research for Rare Diseases (CCRRD)

On November 3, 2016 the Rare Diseases Clinical Research Network (RDCRN) hosted the 4th Conference on Clinical Research for Rare Diseases (CCRRD) in Washington D.C. The Lysosomal Disease Network’s then-current fellows Michael Flanagan, PhD; Li Ou, PhD; Reena Kartha, PhD and Kwangchae Yoon, PharmD; and past fellows Zoheb Kazi, MD; Mari Mori, MD; Melani Solomon, MD and Joseph Schneider, PharmD participated in this conference. Goals of the conference included discussing the instruction of new investigators in rare disease research methodology; developing a reusable curriculum/syllabus on rare disease research methodology; and stimulation of ideas regarding the unique issues facing investigators engaged in the study of rare diseases.

The following day, the semi-annual RDCRN principal investigators’ meeting, attended by the principal investigators of all of the twenty-two RDCRN research consortia, was held in Washington D.C. Lysosomal Disease Network’s Principal Investigator Chester B. Whitley, PhD, MD, presented an overview of a few of the scientific achievements of the Lysosomal Disease Network (clicking on this link results in a 3.5 MB download to your computer).

NIH-funded LDN Investigators Annual Meetings

The Council of Research Experts (“CORE”) – also known as the NIH-funded Investigators, or Lysosomal Disease Network Investigators – met on Friday, March 4, 2016. Presentation slides from the 2016 meeting can be found here.

The Council of Research Experts also met on Friday, February 17, 2017 in San Diego, California. Dr. Rashmi Gopal-Srivastava’s presentation slides from that meeting can be found here (clicking on this link results in a 7.4 MB download to your computer). Dr. Jeffrey Krischer’s presentation slides from that meeting can be found here (clicking on this link results in a 2.8 MB download to your computer).

Lysosomal Disease Network

Lysosomal diseases are a collection of more than 70 clinical syndromes with incidence rates ranging from 1 in 20,000 live births (Gaucher disease) to 1 in 300,000 live births (Wolman disease). Taken together, lysosomal diseases are responsible for a significant amount of disability and disease burden.

Testing New Therapies

The rarity of each lysosomal disease means that no single medical research center has an opportunity to see sufficient numbers of patients with any one lysosomal disease to effectively describe its full spectrum, or to adequately test any new therapies.

Combined and Integrated Efforts

The combined and integrated efforts of the Lysosomal Disease Network (“LDN”) focus on creating a network of centers with expertise in one or more of these diseases in order to solve major challenges in diagnosis, disease management, and therapy. Solutions to these problems will have a direct impact on patients suffering from lysosomal disease and important wider implications for medical practice.

Lysosomal diseases include:

aspartylglucosaminuria; Batten disease (neuronal ceroid lipofuscinosis (NCL) (infantile, late infantile, juvenile, and adult-onset)); cystinosis; Danon disease; Fabry disease; Farber’s lipogranulomatosis; fucosidosis; galactosialidosis types I, II and III; Gaucher disease types I, II and III; glycogen storage disease; GM1 and GM2 gangliosidoses (infantile, juvenile, and adult-onset); Krabbe disease; lysosomal acid lipase deficiency (LALD) including Wolman disease and cholesterol ester storage disease; alpha-mannosidosis types I and II; beta-mannosidosis; metachromatic leukodystrophy; mucolipidosis types II, III, and IV; mucopolysaccharidosis (MPS) types I, II, III, IV, VI and VII (Hurler, Hurler–Scheie, and Scheie; Hunter, Sanfilippo, Morquio, Maroteaux–Lamy, and Sly syndromes, respectively); multiple sulfatase deficiency; Niemann–Pick disease types A, B and C; Pompe disease; Sandhoff disease (infantile and juvenile-onset); Schindler disease types I and II; sialidosis types I and II; Tay-Sachs disease (infantile, juvenile and adult-onset).

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