Lysosomal Storage Diseases Research Support by NINDS: A Meeting with Patient Voluntary Groups

The DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of Neurological Disorders and Stroke

Lysosomal Storage Diseases Research Support by NINDS:
A Meeting with Patient Voluntary Groups

May 16, 2007

Representatives of patient-advocacy groups met with National Institute for Neurological Disorders and Stroke (NINDS) Director Dr. Story C. Landis, Deputy Director Dr. Walter J. Koroshetz and other NINDS officials on May 16, 2007 at the NIH Neuroscience Research Center in Rockville, MD. The main topic of discussion was the Institute's decision to close the Developmental and Metabolic Neurology Branch (DMNB) as of January 2008 and how NINDS will continue to support research on lysosomal storage diseases (LSD).

Dr. Landis opened the meeting with a brief overview of events related to the DMNB. Acclaimed LSD investigator and DMNB Chief Dr. Roscoe O. Brady recently retired after more than 50 years of government service. While today there is a great deal of research on the LSDs being conducted outside of the DMNB, there was virtually none prior to Dr. Brady's groundbreaking research in his early days at NIH. A pioneer in LSD research, Dr. Brady persevered through the nascent years of research in this field, when most of his peers resisted his theories. His initial studies of and success with Gaucher disease led to breakthroughs in other areas of LSD research, including a treatment for Fabry disease and the identification of new types of LSDs.

"Dr. Brady discovered the [Gaucher] defect. He purified the enzyme. He discovered the science that led to an entire industry," Dr. Landis said. "Because of his work, companies and investigators are now interested in studying the LSDs. We all owe a debt of gratitude to Dr. Brady."

Dr. Brady's status as a visionary scientist drew very strong investigators to the DMNB. Over the years, Dr. Brady taught and mentored a generation of LSD researchers who came to the DMNB to train with him prior to joining the extramural research community, where many of them continue to conduct LSD research and, in their turn, instruct their own students and staff in the performance of LSD research.

At the time of his retirement, Dr. Brady was the sole tenured scientist in the DMNB. Upon his retirement, the Board of Scientific Counselors analyzed the NINDS' intramural program in relation to current opportunities and needs in the field of developmental childhood neurology research and, after much deliberation, a decision was made to close the DMNB.

Subsequently, patients and families who rely on the DMNB staff contacted NINDS with serious concerns about the consequences Dr. Brady's retirement would have on LSD research and on patients formerly seen by branch physicians. At the May 16 meeting, Dr. Landis assured representatives of groups supporting research and treatment on the LSDs that the NINDS and other components of the National Institutes of Health remain committed to their cause. She informed the meeting participants that approximately 87% of NIH funding goes to extramural research through research grants, cooperative agreements and contracts, while approximately 9.5% of the budget goes to intramural research. She also explained that money designated for extramural cannot be used for intramural programs, and vice versa.

Dr. Landis then turned the floor over to Dr. Danilo Tagle, a neurogenetics program director in the Institute's Division of Extramural Research. Dr. Tagle has a long history of interest in the LSDs, including collaborative studies with Dr. Brady and other DMNB staff when he was head of the Molecular Neurogenetics section in the National Human Genome Research Institute's intramural program. Dr. Tagle gave an overview of current opportunities and provided detailed information about the vast array of LSD research currently supported through NIH grants to universities, medical centers, and small businesses. These grants seek to expand our knowledge about and develop new therapies for the LSDs. He pointed out that a number of NIH Institutes support various forms of translational and clinical research relevant to LSDs, including stem cell and bone-marrow transplantation, enzyme replacement therapy, and gene therapy, among others.

Dr. Tagle's overview illustrated the considerable interest outside investigators and private-sector organizations have in the field of LSD research. Several have already spoken with NINDS staff about their ideas to develop treatments for LSD. NINDS is encouraging even more interest by actively soliciting grant applications in this field (see PAS-06-202 and PAS-07-195). In addition, in April 2007, the Office of Rare Diseases published a notice of an intent to re-issue a request for applications for the Rare Diseases Clinical Research Network. Six awards are anticipated for FY 2009. Ten research centers have already been funded through a previous RFA in 2002 of which NINDS is one of the funding NIH institutions, Dr. Tagle noted. LSD investigators have formed various collaborations and networks over the past 3 years in anticipation of this RFA. The NINDS has been supportive of the formation and annual meetings of this group of LSD investigators through an R13 mechanism.

Some of the attendees questioned whether the NINDS would continue to support studies on LSDs for which there is already a treatment. Dr. Landis replied that Institute support for LSDs runs the gamut from basic to translational to clinical research and that, although investigations for some LSDs is obviously farther along than for others, the NINDS is committed to supporting relevant research for all.

"Our goal is to help investigators and companies get started," Dr. Landis said. "And we're starting to see results. We have patents pending, and we have begun to talk to companies about licensing, which is something new for the NINDS." These are, potentially, initial steps towards clinical trials.

The discussion then turned to the future plans of DMNB staff, particularly clinician and pediatric neurologist Dr. Raphael Schiffmann. All members of the DMNB staff will have two years to identify new positions, and Dr. Schiffmann is currently in negotiations with at least two medical centers. The NINDS believes strongly that Dr. Schiffmann will be able to help more people in more ways in the private sector and the agency has agreed to pay his salary for the first three years, donate critical DMNB laboratory equipment to Dr. Schiffmann's new employer, and transfer existing tissue samples to Dr. Schiffmann's new location, pending approval by the appropriate authorities here and at his new institution. Details are expected to be finalized in the next several months, and Dr. Landis promised to keep the LSDs community informed about new developments.

"Raffi has created a number of collaborations, and they should continue," Dr. Landis said. "It is possible that several essential personnel currently working in the branch will accompany Dr. Schiffmann to his new facility, as well. We expect that patients currently being treated by Dr. Schiffmann here at the NIH will be able to continue to see him at his new location, and we are taking steps to ensure that the resources developed and collected by the DMNB remain with him." Dr. Landis reassured the attendees that if Dr. Schiffmann does leave NINDS to start a new facility that the staff at NINDS will make sure that current patients would not be negatively impacted due to a potential time lapse between the possible closure of the DMNB and the opening of a new lab at another location. Dr. Landis went on to describe the broad-based planning process currently under way at NINDS, including approaches to encourage studies of treatments for rare diseases. She and Dr. Tagle described the promise of therapeutics research and the importance of expanding such efforts through extramural research programs, including those directly supported by NIH. Dr. Landis mentioned that, as part of the planning process, the Institute would solicit ideas from voluntary health agencies and the public. (Shortly after the meeting, an invitation to submit comments went live on the Institute's home page at http://www.ninds.nih.gov/.)

Attendees expressed their gratitude to Dr. Landis and her staff for organizing the meeting and for working so hard to generate a positive future for research and treatment on the LSDs.

"I think it's extraordinary that you would take the time to have this meeting," said Jonathan Jacoby, Executive Director for the Hide and Seek Foundation for Lysosomal Disease Research. "We all really appreciate it."

Dr. Landis concluded the meeting by asking the participants to share what they learned with their members, and invited them to contact her with any further questions or concerns. "You and your members have been extraordinary partners with the NINDS," Dr. Landis told the advocates. "You have played an important role in what we have done and your continued support and participation are vital to our accomplishing even more in the future. Thank you for coming."

Participant List

Sharon Adams
Director, Meetings and Support Services
National Gaucher Foundation
61 General Early Drive
Harpers Ferry, WV 25425
www.gaucherdisease.org

Micki Gartzke
Director of Education and Awareness
Hunter's Hope Foundation
4075 Stowell Ave.
Shorewood, WI 533211
www.huntershope.org

Jonathan Jacoby
Founder
Hide & Seek Foundation for Lysosomal Disease Research
4123 Lankershim Boulevard
N. Hollywood, CA 91602
info@hideandseek.org

Jack Johnson
Executive Director
Fabry Support & Information Group
108 NE 2nd St.
PO Box 510
Concordia, MO 64020
www.fabry.org

Howard Monderer
Mucolipidosis IV Foundation
3210 Leland Street
Chevy Chase, MD 20815

Paul Murphy, Founder and Past President
ISMRD
P.O. Box 328
Dexter, MI 48130
info@ismrd.org

Dr. Gary Schwartz
Mucolipidosis IV Foundation
6360 Claridge Drive North
Frederick, MD 21701

Cate Walsh-Vockley, MS, CGC
National Niemann-Pick Disease Foundation
Medical Genetics
Children's Hospital of Pittsburgh
3705 Fifth Avenue
Pittsburgh, PA 15213
NNPDF
P.O. Box 49
401 Madison Ave., Suite B
Ft. Atkinson, WI 53538

NINDS Staff

Dr. Story Landis
Director, NINDS
Sl122c@nih.gov

Dr. Walter Koroshetz
Deputy Director, NINDS
koroshetzw@mail.nih.gov

Marian Emr
Director, Office of Communication and Public Liaison
Me20t@nih.gov

Steve Markowski
Public Liaison Officer, Office of Communication and Public Liaison
markowskis@mail.nih.gov

Heather Rieff, Ph.D.
Health Science Policy Analyst, Office of Science Policy and Planning
rieffh@mail.nih.gov

Carol Rowan
Chief, Public Inquiries, Office of Communication and Public Liaison
cr37e@nih.gov

Paul Scott, Ph.D.
Director, Office of Science Policy and Planning
ScottP@mail.nih.gov

Dr. Danilo Tagle
Program Director, NINDS
Dt39y@nih.gov