THE MPS PROJECT a comprehensive GeneticaLens database on the MPS disorders, a project proposed for development over a 2-3 year period. The proposal is designed as a means for facilitating the diagnosis and treatment of the MPS disorders, and to stimulate future research in this field.

Extensive visual documentation of the signs and symptoms associated with MPS disorders and current available palliative and targeted therapies for disease-related complications will be provided. The information collected will be saved in a searchable, user-friendly interactive format. The material when completed will be distributed to multiple potential users (professionals in healthcare, research, and education; as well as families and individuals who have MPS).

The first MPS disorders to be documented are MPS-1 (also known as Hurler, Hurler-Scheie, and Scheie syndromes to describe the different clinical variants) and MPS-IV (also known as Morquio Syndrome)

This is an investigator-initiated pilot research project ("the MPS-1 Project") that will be carried out by co-investigators Dr. Gregory Pastores and Louise Tiranoff. through New York University and Louise Tiranoff Productions (GeneticaLens).

WHAT IS MPS-1?
MPS-1 is a disease caused by a deficiency of the enzyme alpha-L-iduronidase and resulting in a build-up of complex carbohydrates (GAGs) in the lysosomes of cells. What results is a breakdown of the cellular, tissue and organ systems, leading to:
1. impaired cardiac and pulmonary function
2. delayed physical development
3. deformities of the skeleton and joints, with short stature
4. reduced physical endurance, and
5. impaired mental function (in moderate to severe cases)

Most patients with moderate to severe disease die before adulthood as a result of complications from the disease.

The MPS PROJECT (MPS-1)
The main aims of The MPS PROJECT (MPS-1) are to offer a narrative and visual delineation of MPS-1, highlighting the wide heterogeneity and variable rate of disease progression in individual patients.This section will include instruction on the means to establish the clinical diagnosis, the requisite genetic tests, and genetic counseling offered to confirmed cases. Additionally, the means to establish the pattern and severity of disease in diagnosed patients will be outlined.

Specifically, the program will contain:

1. First hand accounts of what it is like to have the disease and appropriate measures taken to address disease-related complications

2. Serial follow-up to tracking the natural history of disease and the impact of therapies

3. The examination of the validity of selected clinical end points, by providing baseline (pre-treatment) findings and performance during certain timepoints

4. Examples of therapeutic applications such as physical therapy; focusing on range of motion and walking difficulties and how these influence activities of daily living

5. Examples of educational strategies to facilitate inclusion of the children and young people with MPS into the mainstream educational system

BROAD, LONG-TERM AIMS:

The broad, long-term aims of the MPS-1 Project are as follows:

1. To create and disseminate an information system on MPS disorders*

This would provide information on symptoms and therapies to users throughout the world. The uniqueness of this system is its wide range of video content, which will be created with GeneticaLens (GL) protocols. Proposed content includes:

a. Diagnostic video clips and video documentary case histories of individuals with the disorder providing examples of a range of symptoms and different levels of severity.

b. Videos & texts on the work of expert researchers and clinicians

c. Educational videos directed at families - including specific issues which healthcare professionals, teachers and educators need to address when working with people with MPS-1

*(eventually to cover all ten MPS disorders, but possibly to begin with MPS-1,2,4,& 6.)

2. To develop an interactive, closed-server or internet-based platform

This will allow users to search content and efficiently target their own needs. Diagnostic information will be made available through a "decision tree" model to allow users to eliminate incorrect diagnoses down to several likely diagnoses. Once a diagnosis is suspected, the user can access video clips to narrow the choices in an effort to confirm the diagnosis. Once the precise diagnosis is obtained, then available treatment options and appropriate therapies can be searched using keywords. Subjects will be searchable by diagnosis, age, and other variables.

Users include:

a. Health care professionals seeking help with a diagnosis or information on appropriate treatment plans. Guidance can also be provided to help physicians with establishing the pattern and severity of disease in the patients, and the appropriate types of monitoring for potential disease-related complications.

b. Individuals with the disorders, who are searching for information to see if a certain diagnosis is pertinent to them. The site will provide relevant information for individuals to take to their personal physician who will then provide a final diagnosis or make a referral to a specialist.

c. Federal agencies and lawmakers involved in the regulatory pathway leading to the approval of new indications. Visual documentation of the progress made as a result of therapies can have a positive impact on the process used by federal agencies to appropriate funds towards the development of orphan products.

d. Other users involved in the delivery of healthcare, such as insurance companies, who need to know about the disease, what therapies are available and how they can be applied so that the level of reimbursement can be improved.

3. To provide access to video and text information in a variety of formats

This will be especially useful in situation wherein access the world-wide-web is not available. Supplementary CD's containing videos and information created for the website will also be distributed separately and the videos created for the internet site will also be used in other venues - such as Continuing Medical Education courses, Grand Rounds, educational mailings, and group presentations.

SPECIFIC AIMS FOR PROTOTYPE PROJECT:

1. Create educational documentary videos on MPS-1, specifically on issues relating to the diagnosis and management of those affected with MPS-1, to serve professionals and families and all those concerned with the disorder. To supplement the video documentaries, create diagnostic clips illustrating symptoms of MPS-1, giving the users immediate and efficient access to visual images, which can help clarify the text criteria. In addition, provide comparative video data using some or all of the following GenticaLens features:

a. Longitudinal video data using previously filmed video of the subject with MPS-1 to see the effect of the disorder at different stages of development, or to see the effects of therapy over time (GL feature "Longitudinal Views"). These assessments should help in determining the impact of intervention on patient's functional quality of life and well-being, and comparative studies of generic and disease-specific quality of life instruments.

b. Video taken before and after therapies, including pharmacological interventions, in order to study and track the specific effects, and possible side effects. (GL feature "Before & After").

c. Video comparing typical unaffected age-matched individuals to individuals with MPS-1, in order to study the impairments caused by MPS-1, against a yardstick of "normal" functioning. For example, show the range of motion of a typical person and match with the range of motion of an individual with MPS-1. (GL feature "typical child/adult") when performing activities of daily living or engaged in sports.

2. Create an interactive searchable web site which will allow people to easily and logically find the information and videos, including case histories and patient and family testimonies describing the experience of getting the diagnosis of MPS-1.

3. Develop a database of subjects with this disorder who have given their consent to be photographed and interviewed.

SUMMARY

The development of an information database on MPS-1, and eventually all the MPS disorders, is critical not only for patient support but also for research and development of therapies and products to address the severe symptoms of these disorders. The MPS Project will link visual data to existing registries as well as be instrumental in enrolling new subjects into clinical trials or in starting new registries. The project will be designed to provide such features as consistent description categories/tags to facilitate comparison across various clinical subtypes, to facilitate timely and accurate diagnoses. The MPS project will also include extensive filming of subjects and aspects of their lives, their families, their treatments that best reveal the impact of the symptoms. Also GeneticaLens will be a useful tool in post-marketing efforts and follow-up studies to track the effects of therapy on individuals, to establish monitoring and treatment