The Growing Promise of
Gene Therapy Approaches
to Rare Diseases

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 are co-sponsoring a workshop entitled “The Growing Promise of Gene Therapy Approaches to Rare Diseases.” The workshop will review the state of current gene therapy approaches; identify challenges and strategies to overcome those challenges; and discuss 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, will be among the speakers on a panel, and will talk about gene therapy for lysosomal diseases beginning at 10:00 a.m. central time on August 20th. This joint meeting will facilitate 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 will convene at National Institutes of Health (Main Campus), NIH Clinical Center (Bldg. 10), Masur Auditorium, 10 Center Drive, Bethesda, Maryland, 20892. There is no admission fee to attend, and the workshop also will be videocast live. Please note that registration is necessary, whether attending in-person or by live videocast.

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.

5th Conference on
Clinical Research For
Rare Diseases (CCRRD)

The Rare Diseases Clinical Research Network will convene their 5th Conference on Clinical Research for Rare Diseases (CCRRD) on November 19, 2018 in Rockville, Maryland, for the benefit of new investigators, trainees, junior faculty, and others interested in rare disease research methodology. Conference attendees are encouraged to submit an abstract, which will be reviewed by the planning committee. The abstracts selected by the planning committee will be invited to be displayed as a poster during the conference. Four trainees with the highest-ranked abstracts will be invited to present their work orally during the meeting. Abstract submission deadline: October 22, 2018. Instructions-to-authors for abstracts and posters are here (scroll down).

The 5th CCRRD will take place at the Hilton Rockville Hotel & Executive Meeting Center. A discounted room rate is available until September 11, 2018. Attendees are responsible for making their own hotel and travel arrangements for the meeting. Use the hotel’s group-booking codes (scroll down) when making your hotel reservation.

Attendees must register for the meeting. Registration Deadline: November 12, 2018. Registration is $100 and includes: meals, refreshment breaks, and meeting materials. Travel awards up to $750 are available on a competitive basis for trainees, fellows, and junior faculty. Candidates must register for the meeting, submit an abstract, and submit their current NIH Biosketch before they can be considered for a travel award. All requests for travel awards are judged by a committee from the Rare Diseases Clinical Research Network. Travel Award recipients will be notified by November 5, 2018. The informative CCRRD flyer would look great on the bulletin boards in your research institution!

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.”

A Rare Opportunity for
Young Researchers:
The Rare Disease
Clinical Research
Training Program

The Rare Diseases Clinical Research Network (RDCRN) annually offers 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.)

This academic-year-long course consists of both in-person and remote sessions providing the tools and mentorship 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 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 2019 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.

Twenty applicants will be accepted for a “funded” position. This funding will cover $1,000 of travel costs for the program. 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. Applicants are requested to submit the following: their CV; a 1-page description of their proposed rare disease research project; and a letter of commitment from their supervisor regarding the 10% protected-time for this training program, as well as attesting to the applicant’s rare disease research aptitude. A second letter from an outside mentor is encouraged, in order to show community support for the applicant.

The application deadlines for the 2018-2019 Training Program have passed. When information is released about the 2019-2020 Training Program, it will be available here.

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.

NIH-funded
LDN Investigators
2017 Meeting

The Council of Research Experts (CORE) – also known as the NIH-funded Investigators, or Lysosomal Disease Network Investigators – 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).

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 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. Chester B. Whitley, PhD, MD, LDN principal investigator, presented an overview of a few of the scientific achievements of the Lysosomal Disease Network.

NIH-funded
LDN Investigators
2016 Meeting

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.

Lysosomal Disease Network

Lysosomal diseases are a collection of more than 70 clinical syndromes with incidence rates ranging from 1 in 20,000 (Gaucher disease) to 1 in 300,000 (Wolman disease) live births; taken together these conditions 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 disease to effectively describe the full spectrum of each disease or adequately test any new therapies.

Combined and Integrated Efforts

The combined and integrated efforts of the 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 implications for medical practice.

Lysosomal diseases include:

aspartylglucosaminuria; Batten disease; cystinosis; Danon disease; Fabry disease; fucosidosis; galactosialidosis types I, II & III; Gaucher disease types I, II & III; GM1 gangliosidosis (infantile, juvenile, 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 types I, II, III, IV, and VI (Hurler, Hurler–Scheie, and Scheie; Hunter, Sanfilippo, Morquio, and Maroteaux–Lamy syndromes, respectively); multiple sulfatase deficiency; neuronal ceroid lipofuscinosis (infantile, late infantile, juvenile, adult); Niemann–Pick disease; Pompe disease; Sandhoff disease (infantile, juvenile); Schindler disease types I and II; sialidosis types I and II; Tay-Sachs disease (infantile, juvenile and late-onset).

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