RESEARCH PROJECTS TAKING PLACE
AT THE B.I.R.D FOUNDATION

The Association for Rare Diseases
MAURO BASCHIROTTO

The Association was founded in 1989 by Anna and Giuseppe Baschirotto, to remember the suffering endured by their beloved son Mauro, who died at the age of sixteen, two years earlier.
It is a non-profit organisation registered at the regional registry of Volunteer Organisations. The purpose of the organisation is to conduct studies and research into diseases that are almost always characterised by sometimes insurmountable difficulties in diagnosis and treatment, in order to try and alleviate the operational and emotional burden faced by patients and their families. Each pathology varies greatly as does each individuals’ situation, and as a result it is very difficult for people in the health industry to perceive the complex reality that each patient must confront. It is also important to remember that rarely are there appropriate drugs available to treat these conditions, since they are too costly and not sufficiently sought after. Filling this gap in the areas of assistance and understanding, is another function of the organisation which, has dedicated itself completely to the fight against these diseases, (over five thousand have been identified!) through strategic initiatives including:

• Epidemiological studies to identify the qualitative and quantitative incidence of various diseases in the surrounding region, and to maintain a permanent observation of this

• Consultation and assistance service for patients and their families, and also for doctors and other health care professionals. This initiative is supported by numerous specialised doctors and has resulted in the formation of close ties with Institutes and specialised centres both locally and internationally. It also involves connection to major international databases which allows researchers to instantly identify other laboratories and groups that occupy themselves with specific pathologies and that in turn are able to make a quick diagnosis

• The formation of sections, within the Association, for various areas and/or groups of diseases, for which there are no existing Associations already

• Biomedical research into areas which have been strategically chosen, also through various editions of The International Award for Genetic Therapy, aimed to encourage biomedical research into cures for many genetic diseases. The award is comprised of financial assistance to the researcher that presents the project and of a contribution to the Institute from which the researcher is based at

• Work-shops on single diseases and scientific meetings in strategically chosen areas, with attendance from leading scientists, in order to keep practitioners up to date with all the most recent findings and to encourage discussion and new alliances

• The formation of task-forces for specific diseases, with multi-centre research projects, with international interests, co-ordinated by the Association and incorporating the involvement of true researchers, both clinical and epidemiological. Examples of this are: Metachromic Leucodystrophia, Lesch-Nyhan, Spinal Muscular Dystrophy and APECED.

• Starting up and Institute for Scienticfic Biomedical Research into rare diseaseas at Costozza di Longare (Vicenza).

DIAGNOSTIC REHABILITATION
PILOT CENTRE
for the
DIAGNOSIS, THERAPY AND TREATMENT OF RARE DISEASES

The Institute for rare Diseases (B.I.R.D) is based in Costozza di Longare in the province of Vicenza (between Vicenza and Padua and only a few minutes from the Vicenza East exit of the nearby freeway). The institute partly resides within an historiacal Villa named “Villa Morlini Trento”, a building of great prestige and importance back in the fifteenth and sixteenth centuries. Lining the walls of its many grand rooms one can find numerous precious frescos. The villa is most appropriate for hosting meetings and conferences, stages, courses and offices.
The rest of the institute comprises of a Church, an old factory which has been renovated in order to host overseas guests or patients and their families, and also a newer factory with a floor space of around 1,800m2 which has been dedicated for use as laboratories, clinics, and gymnasiums for rehabilitation and physiotherapy. There is also a large garden surrounding these many buildings which covers an area of about 30,000m2 which would be an ideal place to set up areas for hydrotherapy and therapy with horses.
The most important activities that are intended to take place at the institute are as follows:

• Advanced Genetic/Molecular Diagnoses of pathologies which are classified as rare diseases.

• Research and clinical application of new treatments which include gene therapy, both pharmacological and enzymatic.

• Research and clinical application of new rehabilitative techniques primarily in the area of motor function, in diurnal and continuing cycles.

• Information and assistance services for patients suffering from a rare disease, their families, doctors and other health care professionals.

• Organisation of meetings, stages and training to keep doctors and other health care professionals up to date.

• Meetings between patients, families, clinicians and researchers.

• Development and management of a bank of biological materials, who’s function would be to conserve any precious samples provided by patients suffering from a rare disease. These samples would be available to anyone in the scientific community, in order to try and promote further research and confirm diagnoses already made.

• Update the registry and materials of similar banks which already exist.

Presently, about 600m2 of floor space is used by molecular, genetic and cytogenetic laboratories, where a group of very talented, young researchers have already participated in numerous studies and have made very interesting findings.

RESEARCH PROJECTS TAKING PLACE AT THE B.I.R.D FOUNDATION

1. Project: MLD (Metachromatic leukodystrophy) and other Lysosomal Diseases
Metachromatic leukodystrophy (MLD) is a genetic, lysosomal disease which causes damage to the myelin sheath surrounding nerves, and causes progressive paralysis of all motor function.
The projects has been funded since 1992 and its aim is to find a gene therapy to treat this disease and other similar lysosomal diseases.
In March 2001, an article on the resounding findings of this project was published in “Nature Medicine”, that is, regression of the neurological damage seen in experimentation on animal models, which also supplied important information about the passage of the lentivirus (vector which transports the gene) in the lobe that wasn’t injected. This knowledge enables us to identify possible uses for this method in other diseases such as Alzheimer’s, Parkinson’s etc.
Almost all the Italian families affected by this disease are directly connected to the Association of Rare Diseases.
The project is conducted by Dr. Antonella Consiglio and is directed by Dr. Claudio Bordignon.

2. Project: SMA (Spinal muscular atrophy)
Spinal muscular atrophy (SMA) is a serious genetic disease, in which there is a defective or missing gene, and this provokes severe neurological damage in patients effected, with progressive weakness in all motor and respiratory function.
The project has been funded since 1996 and its aim is to find a gene therapy to treat this disease.
Then results obtained so far are very encouraging, in fact, presently experimentation is taking place in murine models.
The project is directed by Prof. Patrick Aebischer.

3. Project: Lesch-Nyhan
Lesch-Nyhan is induced by a genetic defect in the DNA bases, with consequent renal and neurological damage. Some cases also present with severe forms of autoaggressiveness with lesions on the lips, tongue and hands which don’t heal.
Not only are all the Italian patients referred to the Association of Rare Diseases, but also English, Romanian, Hungarian, French, and Swiss patients.
The project has been funded since 1996 and its aim is to correctly characterise the genetic defect responsible and then find an appropriate therapy for its treatment.
Through the laboratories at B.I.R.D, it has already been possible to study the genetic mutations of many patients and to offer an important diagnostic service. 12 new mutations have been found thus far.
Pharmacological experimentation, which has been approved by the ‘Comitato di Bioetica dell’Ordine dei Medici Chirurghi ed degli Odotoiatri’, takes place within the Institute by Dr. Alessandro Salviati in collaboration with Prof. Nyhan and Prof. Junnah.

4. Project: A.P.E.C.E.D (Autoimmune Poly Endocrinopathy Candidiasis Ectodermal Dystrophy) and rare endocrinopathies
A.P.E.C.E.D (Autoimmune Poly Endocrinopathy Candidiasis Ectodermal Dystrophy) is a serious genetic autoimmune Endocrinopathy that provokes damage in many organs and also a predisposition to recurrent bacterial, viral and mycological infections.
We have had numerous families referred to us that come from areas particularly affected by this disease: Veneto, Sardinia and Finland.
The project has been funded since 1996 and its aim to is get a better understanding of the function of the gene involved in the autoimmunity seen, and to find a suitable treatment.
The project is conducted by Dr. Scott and is co-ordinated by Dr. Antonarakis.

5. Project: VANNA
This project looks at rare forms of tumour and the genetic aspects of familial tumours. It was started in memory of a young teacher from the local community and its aim is to find the genetic causes of these diseases in order to identify appropriate therapies.
This focus of this project are the BRCA1 and BRCA2 genes, which may be able to help us identify the genetic predisposition or numerous cancers such as breast and ovarian cancer.
The project has been funded sin 2000 and is co-ordinated by Dr. Mario Stella.

6. Project: Haemochromatosis
Haemochromatosis is an hereditary disease characterised by excessive absorbance of iron. This causes damage to numerous organs including the liver, pancreas and heart which has serious consequences, especially in older patients.
The European Project for Haemochromatosis from the Foundation of rare Diseases was initiated in 1998. Its aim is to study the function of the responsible gene with the use of a very sophisticated and advanced machine known as microarray, which uses nanotechnology.
12 laboratories from 10 European countries participate in this project.
The project is conducted by Dr. Massimo Carella and is co-ordinated by Prof. Paolo Gasparini.

7. Project: Hereditary Ataxia
The hereditary ataxias are a group of genetic neurological disorders that cause cerebellar atrophy and progressive damage to the Nervous System.
The project begun in 1999 and it aims to offer diagnostic support to patients in the area of molecular genetics and to study the causes of these numerous disorders in the hope that one day a suitable therapy will be identified, even a rehabilitative therapy.
The project is directed by Prof. Massimo Pandolfo.

8. Project: Epilepsy
Around 200 hereditary and chromosomal diseases are accompanied by epileptic manifestations.The general objective of this research project is to identify and characterise the genes responsible for idiopathic focal epilepsies with a monogenetic inheritance. The patient samples come from various Italian laboratories and also from other countries such as Canada, Belgium etc.
The project is directed by Prof Massimo Pandolfo.

9. Project: Laura
An event in many diseases is mental retardation related to chromosomal anomalies and to genetic diseases. The project began in memory of Laura, a young student that died in a fire at her school in Legnano, Verona.
It aims to be a service for the Community, Hospitals and Educational Centres to widen the understanding of the ties between the effects of the disease (mental retardation) and genetic defect.
The project is directed by Dr. Alessandro Salviati.

10. Project: Juvenile Parkinson’s
This form of Parkinson’s Disease begins at a young age and is hereditary. It is a neurological disorder that is slowly progressive and degenerative.
The project aims to study the gene responsible.
The project is directed by Dr. Massimo Pandolfo.

11. Project: Mitochondriopathy
Mitochondrial disorders are a group of diseases characterised by an enzymatic deficit that carries consequences at both a single organ level as well as a multi-systemic level. The defect is caused by a mitochondrial malfunction, these are the organelles that are responsible for producing the energy required by the cell for all of its functions.
The project began in 2001 and it studies the causes of these disease, however it also aims to make available a wide range of diagnostic tests.
The project is co-ordinated by Dr. Massimo Zeviani.

12. Project: Multiple Chemical Sensibility
This is a systemic disease that causes severe allergies and intolerance to multiple chemical agents. Presently it often goes undiagnosed and is underestimated in its severity as there is a lack of understanding in the community.
The project began in 2002 and it aims to identify the cause of the disease and to eventually find an appropriate therapy that can help to manage its symptoms.

13. Project: Rett Syndrome
Rett syndrome is a neurodegenerative disease that generally effects young girls and is characterised by developmental regression and the loss of competence in tasks previously preformed.
Through his project it has been possible to study and characterise the genetic defect responsible and to offer molecular diagnosis to most patients.

14. Project: Prader Willi and Genetic Obesity
Prader Willi Syndrome is a multi-systemic disorder characterised by retarded growth, followed by obesity, increased appetite and moderate mental retardation.
The project aims to study the genetic causes of this and other obesities, and the starting up of numerous experimental therapies.
Presently, research into the WNT gene is taking place on numerous families affected by severe obesity.
Within B.I.R.D resides the head office of the International Association of Prader-Willi, which has members from over 45 different countries around the world. The Association acts as a reference point for diagnostic development and for the study of all the necessities of those countries which are not capable of offering a diagnosis to patients (presently half). An International Library for Prader-Willi has also been established in collaboration with some of the most important international scientists.
The project is directed by Prof. Roberto Vettor.