Latest Research News and Announcements (updated May 2010)
Please note: The following overview of recent research into the Niemann-Pick diseases is provided for your information only. By providing this information, the NPDG (UK) does not advocate or endorse the findings. The information provided is in no way intended to replace professional medical care and should not be used as a basis for diagnosis or choice of treatment. All users are strongly advised to seek the advice of their local healthcare team before acting on any information provided herein, as no responsibility can be accepted by the NPDG (UK). If you have any questions about the information provided please contact the Niemann-Pick Disease Group, email niemann-pick@zetnet.co.uk or telephone 0191 415 0693 or Elizabeth Jacklin, Niemann-Pick Clinical Research Nurse, email elizabeth.jacklin@cmft.nhs.uk or telephone 0161 701 2967.
To read the Niemann-Pick Disease Group (UK) Research Strategy, please click here.
Update from Genzyme on Acid Sphingomyelinase Deficiency (ASMD) Clinical Trials (May 2010)
Genzyme completed a Phase 1 clinical trial in 2009 that was designed to evaluate the safety of single-dose administration of recombinant human acid sphingomyelinase (rhASM) as a potential treatment for ASMD (also known as Niemann-Pick Disease Types A and B). We are conducting further preclinical research and engaging regulatory agencies in discussion about the available preclinical and clinical data, as well as preliminary plans for the Phase 2 trial.
The Phase 1 clinical trial results were presented publicly at two scientific meetings last year and are being prepared for publication. We are also planning to publish results from an international, retrospective natural history study of ASMD.
Genzyme want to once again thank the participants of the Phase 1 trial for their contribution to our understanding of rhASM and acknowledge the ongoing support of the patient community; Theyl keep the community updated as our development plan continues.
Let's Talk About Research
A research meeting on NPC was recently held at Royal Manchester Children's Hospital on 1st December 2009. You can view the various presentations by clicking here.
Ara Parseghian Medical Research Foundation Newsletter Winter 2009
Issues Regarding Curcumin Therapy for NPC (November 2009)
Use of various supplements in NPD patients is routinely discussed by families and is a challenging issue. There is often little data on use of the supplements in children and teens, or even in adults, for that matter. There is also limited data on reasonable dosing and on potential side effects. One such supplement, curcumin, has been discussed over the last few months on the NNPDF list serv. There have also been concerns raised in the scientific community that higher doses of this compound are not as effective as lower doses, and in fact, may be toxic rather than being helpful to patients. View a summary of the limited data on use of curcumin.
Dietary Modification of Children on Miglustat therapy (Zavesca) (November 2009)
Helena Champion is a dietician who works at Addenbrooke’s Hospital, specialising in supporting and modifying the diets of children with metabolic disorders. Her recent work includes dietary modification of children on Miglustat therapy (Zavesca); as part of a trial at AddenbrookesHospital. Helena presented a Breakout session at the NPDG (UK) Annual Family Conference 2009, which reviewed this trial and looked at the benefits and practicalities of following a low disaccharide diet while on Miglustat therapy. Helena’s presentation can be viewed here, along with a poster detailing the study results.
Contact a Family have produced an informative leaflet regarding medical information found on the internet.(November 2009) To view please click here.
Expression of Hope II: Inspiration through Art (September 2009)
We are very pleased to announce that a picture painted by Roy Green, age 33, NPC, has been chosen to be part of Genzyme’s Expression of Hope II exhibition. Expression of Hope II: Inspiration through Art, is a global program of goodwill and awareness featuring works of art by people whose lives have been touched by lysosomal storage disorders (LSDs). Genzyme envision the beautiful and moving pieces of art to be both celebrations and reflections of the amazing power and spirit of the people they have come to know through the years. Expression of Hope II will travel to cities around the world, generating awareness and understanding of the incredible strength and courage of the thousands of people worldwide living with LSDs, and will be viewed by others in the LSD communities. Roy provided the following statement, which can be found on the Expression of Hope II Website, along with his artwork: “During the week I am often found delving into the realms of art, music, radio, textiles, travelling and cinema. At present I'm working on a couple of mixed media projects, one of which I have just completed. I feel my interpretation of Monet's, "San Giorgio Maggiore at Sunset" using paint, pastel and tissue, portrays the ultimate sunset with the enhanced use of colour and texture. “ Roy’s painting was selected by a juried panel from the Center for Art and Community Partnerships at Massachusetts College of Art and Design, in Boston, Massachusetts, U.S.A .The panel viewed all of the submitted works and selected eighteen pieces based on the technical and emotive quality of the art along with its ability to infuse the viewer with insight and appreciation of the hope and spirit of the person portrayed.
Congratulations Roy! View the Expression of Hope II Gallery
A Phase 1 Trial of Recombinant Human Acid Sphingomyelinase (rhASM) Enzyme Replacement Therapy in Adults with ASM Deficiency (ASMD) (September 2009)
Dr Margaret McGovern writes: " Dr. Wasserstein and I, and the entire Niemann Pick Disease team, want to thank the patients who volunteered and made it possible to complete the Phase I study of Recombinant Human Acid Sphingomyelinase (rhASM) Enzyme Replacement Therapy in Adults with ASM Deficiency (ASMD). The poster we presented at the International Congress for Inborn Errors of Metabolism is now available for you to see. We also will be presenting these results at the American Society of Human Genetics Meeting in October 2009. The study was very important. It told us what the safest starting dose for the enzyme should be. It showed that there were some side effects of the drug that usually occurred between 24 and 48 hours after the infusion but that resolved quickly. We also learned what the important blood tests will be to monitor in future trials. It is a very exciting first step in getting a drug approved for the treatment of Niemann Pick disease and we are very happy to share these results with you. Sincerely Margaret M McGovern, MD, PhD, Professor ad Chair of Pediatrics, Stony Brook University School of Medicine, margaret.mcgovern@stonybrook.edu".
Cyclodextrin Overcomes Deficient lysosome-to-endoplasmic reticulum transport of cholesterol in Niemann-Pick type C cells ( Lina Abi-Mosleh, Rodney E. Infante, Arun Radhakrishnan, Joseph L. Goldstein, and Michael S. Brown) to read the full abstract click here
New UK LSD Collaborative Group Established (September 2009)
Representatives from UK Lysosomal Storage Disorder Patient Organisations have joined forces to create a strong lobbying and action group for LSD patients and their families in the UK. The Group is made up of patient representatives from the Niemann-Pick Group (UK), the Gauchers Association, The Society for Mucopolysaccharide Diseases (the MPS Society), the Batten Disease Family Association, and the Association for Glycogen Storage Disease. The Group first met in January 2007 to discuss common issues, such as working with the pharmaceutical Industry, the development of homecare services for patients, new born screening, the development of metabolic networks in the UK, the need for research into the brain, and representation on the Health Technology Assessment longitudinal study into enzyme replacement therapy (ERT) for LSDs.
Further information can be found in the Group’s Newsletter
Mechanisms and consequences of impaired lipid trafficking in Niemann–Pick type C1-deficient mammalian cells
(Barbara Karten a, Kyle B. Peake b, Jean E. Vance) To read this abstract, please click here.
New Niemann-Pick Mouse Engineered (August 2009)
It is with good reason that Edward Schuchman calls Niemann-Pick Disease type A a “very, very challenging disease.” The neurodegenerative disorder is rare, kills those who have it by age 2 or 3, and has no known cure. But in May, Schuchman and his research team at Mount Sinai Medical Center in New York announced a breakthrough in their work on the disease, read more.
Psychosocial Aspects of Patients With Niemann-Pick Disease, Type B (July 2009)
Click here to read the full abstract.
News from Denny Porter and Nicole Yanjanin at the NIH (July 2009)
A new therapeutic trial was approved this week by the NICHD IRB. The name of this study is Biomarker Validation for Niemann-Pick Disease, type C: Safety and Efficacy of N-Acetyl Cysteine. This study still has to be reviewed by the FDA, but the NIH are hoping to start enrolling patients this September. Click here to read more.
APMRF Annual Scientific Conference Highlights (June 2009)
In June, ninety researchers form around the world convened a meeting in Tucson, Arizona to discuss the advances in Niemann-Pick Type C (NP-C) disease research. To read more about this Conference, please click here. A summary of the presentations can be found in the APMRF newsletter.
Cyclodextrins promote protein aggregation posing risks for therapeutic applications
Min S. Wang, Shanta Boddapati, Michael R. Sierks (June 2009)
To read the full article, click here.
Recommendations on the diagnosis and management of Niemann-Pick disease type C. (June 2009)
An expert panel was convened in Paris, France in January 2009 to discuss best care practices for NP-C. This paper reviews current literature on key aspects of the clinical management of NP-C in children, juveniles and adults, and provides recommendations based on consensus between the experts at the meeting. Click here for more information.
Actelion Pharmaceuticals Ltd announces the launch of Zavesca® (miglustat) in the UK and Republic of Ireland (MAY 2009)
Actelion Pharmaceuticals Ltd announces the launch of Zavesca® (miglustat) in the UK and Republic of Ireland the first and only licensed treatment available for people with Niemann-Pick type C (NP-C) disease [1]. NP-C is a rare, genetic disease with significant neurological deterioration that can be fatal and affects infants, children and adults Zavesca® is the only specific treatment available for patients with NP-C disease. Also in 2009, it received approval in the European Union (EU) and is also indicated in the US, the EU and several other countries for the oral treatment of adult patients with mild to moderate type 1 Gaucher disease for whom enzyme replacement therapy is unsuitable or is not a therapeutic option. The use of Zavesca® is supported by over 10 years of clinical trials and post-marketing experience across indications. Click here
NIH Announces New Program to Develop Therapeutics for Rare and Neglected Diseases (May 2009)
The National Institutes of Health is launching the first integrated, drug development pipeline to produce new treatments for rare and neglected diseases. The $24 million program jumpstarts a trans-NIH initiative called the Therapeutics for Rare and Neglected Diseases program, or TRND. Click here to read more.
Report from Zavesca Launch, Berlin, Germany (May 2009)
To read the full report, click here.
Genzyme Trial of rhASM (April 2009)
The Phase 1 trial of rhASM in Niemann-Pick Type B patients has now been completed; click here to read the full statement from Genzyme. We are all very excited about this and will of course keep you up to date with developments. If you have any questions or comments regarding this announcement please feel free to contact our Clinical Research Nurse by email Elizabeth.Jacklin@cmft.nhs.uk , Jackie Imrie, our Clinical Nurse Specialist, can also be contacted for advice by telephone 0161 922 2414 or email Jacqueline.Imrie@cmft.nhs.uk . Alternatively, if you would like further information about our Conference, contact the Central Office on 0191 415 0693, or email niemann-pick@zetnet.co.uk
Actelion announces the launch of Zavesca® (miglustat) in the UK and Republic of Ireland (April 2009)
The first and only licensed treatment available for people with Niemann-Pick type C (NP-C) disease. To read the full press release click here.
World Rare Disease Day (February 2009)
World Rare Disease Day took place on 28th February 2009. The day aimed to raise awareness of rare diseases with policy makers and the public, to emphasize the impact they have on patients’ lives, it highlighted the need to make rare diseases a public health priority and underlined the importance of having designated Centres of Expertise. Other main objectives of Rare Disease Day were to: strengthen one voice of patients; give hope and information to patients; bring stakeholders closer together; co-ordinate policy actions in different countries; inspire continued awareness and understanding of rare diseases and get equity in access to care and treatment . Events took place in all 23 participating countries, including the UK as detailed above. Rare Disease Day
Potential Treatment Options - An Overview (February 2009)
To view a question and answer presention given at the recent Clinic Day held at the Willink, please click here.
SOAR – NPC - Support of Accelerated Research for Niemann-Pick Disease Type C (February 2009)
SOAR-NPC (Support of Accelerated Research for Niemann-Pick Disease Type C) is a collaborative research project funded by The Addi & Cassi Fund, The Ara Parseghian Medical Research Foundation, Dana's Angels Research Trust, The Hadley Hope Fund and The Hide & Seek Foundation for Lysosomal Disease Research.- click here to read the Progress Report.
High Throughput Screening
SOAR scientists have developed a new test that measures the amount of NPC1 protein in human cells and a key chemical necessary for the test has been made. It is their intention that the NIH Chemical Genomics Center can conduct “high throughput screening” of human cell lines that come from NPC patients, using the most advanced robotic technology. This test will allow SOAR scientists to determine whether one or more of more than 3,000 drugs already approved by the FDA are capable of increasing levels of NPC1 protein in cells, and therefore might be effective in delaying the onset and progression of NPC disease. For more information click here.
Cyclodextrin as a possible treatment for NPC
Click here and here to read about the latest developments with cyclodextrin.
NPC Mouse Models
Ongoing studies in the USA examine several drug combinations in the NPC mouse. These include; miglustat, dietary supplements such as curcumin, and, already approved over the counter drugs such as ibuprofen. You can read more about curcumin and Alzheimer’s here.
Biomarkers
These are chemical markers which are used to measure whether a disease has relapsed or progressed. It has always been difficult to determine bio-markers in NPC. Dr Denny Porter at the National Institutes of Health in Bethesda, Maryland, USA, is currently running a study to evaluate bio-markers in NPC. These findings could lead to a new diagnostic test for NPC, as well as offer the potential to examine changes in biomarker levels during therapeutic efficacy trials. Current activities around this finding include attempts to correlate biomarker levels with disease severity, and to validate these findings in an animal model of NPC.
The NIH are currently recruiting patients and it is hoped that in the future we will also be able to recruit patients in the UK.
Location of Genetic Loci for Severe Obesity (January 2009)
On January 18 2009, Nature Genetics published an early online release of a paper by a large team of European researchers, headed by Philippe Froguel from the Pasteur Institute, Lille, France, that identifies three new genetic loci that account for a substantial amount of childhood-onset and severe adult obesity. In addition to the previously identified FTO and MC4R genes, the researchers detected significant association of obesity with three new risk loci in NPC1 (endosomal/lysosomal Niemann-Pick C1 gene), near MAF (encoding the transcription factor c-MAF) and near PTER (phosphotriesterase-related gene).
To read more click here.
Chemical Chaperone Therapy – A New Treatment Approach for NPC? (February 2008)
In a recently published article from Washington University in St. Louis, researchers propose a new treatment approach for NPC. The article talks about a discovery that has led researchers to suggest that chemical compounds could potentially “chaperone” mutant protein molecules though cells. The chemical compounds, which act as chaperones, allow the mutant protein to pass through the cells quality control system, and do its job of moving cholesterol out of cells. Whilst this is very exciting news and may lead the way to potential new treatments for NPC, it is unlikely that these treatments would be available in the short term. As with all these things it is not possible to give an exact time scale. Suitable compounds would need to be identified and then these compounds would have to be developed by a pharmaceutical company. Before a drug could be used on patients, it would need to go through animal testing and then Phase I studies, which is the first stage of use in humans. This would initially be done using healthy volunteers. This is a very important part of the process and it can take quite a long time to ensure that the compound is safe and well tolerated. The correct dosage would also need to be ascertained. Following this, a clinical trial would have to be developed and patients recruited. When a trial is finished and the data collected, then the pharmaceutical company would need to apply for a licence to market the drug. All this can take quite a long time! The news of chemical chaperone therapy as a possible treatment of NPC is, however, very positive and exciting news for all of us who are hoping and praying for an effective therapy for this disease. You can be sure that the Niemann-Pick Disease Group (UK) will continue to keep up to date with developments in this area and feed back any information we have. You can read the article by clicking here.
Zavesca (miglustat) receives EU approval for the treatment of progressive neurological manifestations in patients with Niemann-Pick type C disease click here for further information
Cross-Sectional Survey Study of the Natual History of Niemann-Pick Type B click here for further information
NPC1/NPC2 function as a tag team duo to mobilize cholesterol click here for further information
NF- alpha plays a role in hepatocyte apoptosis in Niemann-Pick Type C liver disease. Victoria M. Rimkunas1, Mark J. Graham2, Rosanne M. Crooke2 and Laura Liscum1 click here for further information
Cholesterol Accumulation by Macrophages Impairs Phagosome Maturation Kassidy K. Huynh1*, Elena Gershenzon2* and Sergio Grinstein1,2 click here for further information