Target achieved The first scientific study regarding the Stem Cell research in Amyotrophic Lateral Sclerosis as been published

	"Stem cell treatment in Amyotrophic Lateral Sclerosis" Journal of the Neurological Sciences (2007) Link | Complete Article (Pdf, 382 Kb) | Read the news
	Objective for 2005-2006. PHASE 1 CLINICAL STUDY "CLINICAL APPLICATION OF AUTOLOGOUS MESENCHYMAL STEM CELLS IN AMIOTROFIC LATERAL SCLEROSIS" Author: Dr. Letizia Mazzini, Department of Neurology, Easter Piedmont University, Novara (June 2008) Link | Complete Article (Pdf, 16 Kb)
	OBJECT: Scholarship for project: CLINICAL STUDY IN PHASE 1 "Clinical application of autologous mesenchymal stem cells in amiotrofic lateral sclerosis". Author: Dr. Letizia Mazzini, Department of Neurology, Easter Piedmont University, Novara Link | See project request
	Scholarship extension letter: Display the notice of competition for awarding of a scholarship for project "Clinical Application of autologous mesenchymal stem cells in Amiotrofic Lateral Sclerosis" DISPLAY ACCEPTANCE OF THE DONATION AND NOTICE OF COMPETITION Link | Display the awarding of the Scholarship

Studies are in progress in the Stem Cell Transplant Laboratory of the Regina Margherita Hospital of Turin regarding the mesenchymal stem cells (MSC). The MSC are drawn from a healthy individual and cultivated in a laboratory to be able to transplant them in diseased subjects for therapeutic purposes. In this case, the human MSC are isolated and expanded, originating from the medulla ossium (bone marrow) and driven to differentiation in a neutral sense in vitro.

The differentiation of the MSC into neutral cells is studied by means of biological cellular, molecular and electrophysiological techniques. In particular, the MSC placed in culture with diverse agents of differentiation including ß-mercaptoethanol; dimethyl sulfoxide + ß-hydroxyanisole; trans-retinoic acid and Neural Progenitor Maintenance Medium are able to modify their morphology (assuming a semi-neural aspect), express neural markers (including Nestin, Neuron-Specific Enolase; the antigen Neuronal Nuclear, the type 2 Microtubule-associated Protein and the Glial Fribrillary Acidic Protein) and present currents associated to the K+ channels raised by means of electrophysiological techniques. These cells (MSC) are able to excrete substances which favour the growth of the neurons and their prolongation.

Moreover, to study the capacity of the MSC to slow the progression of the neuronal damage and the eventual regeneration of the damaged nerve tissue, in the Human Anatomy and Legal Medicine laboratory of the University of Studies in Turin, directed by Prof. Alessandro Vercelli, in vivo studies are in progress on an experimental model of amyotrophic lateral sclerosis in mice. As a model, SOD-1 mice are used, that is a carrier of the mutated gene of the superoxide-dimutase of type 1.  Such mutation provokes in mice a clinical picture similar to that of the patients afflicted with the familial form of Amyotrophic Lateral Sclerosis, a disease characterised by the progressive degeneration of motoneurons with consequent atrophy and muscular paralysis.  The human MSC are marked with a nuclear colorant (Bisbenzimide) and inoculated in the spinal cord level. The results obtained to date demonstrate how the MSC inoculated at a spinal cord level of these mice are able to root, migrate, and survive in the long term and reduce the reactive astrogliosis, slowing the progression of the pathology. Such results reflect from a functional point of view in the improvement in the behavioural tests, therefore, in the motor functions in the transplanted mice.  It is our intention to use the MSC to administer substances that prevent the neuronal death in the spinal cord location.

To continue such studies, the use of new instruments are deemed necessary including a laminar flow hood for the manipulation of cellular cultures with UV lamp and empty tap and a large capacity centrifuge counter ventilated for the isolation and expansion of the mesenchymal stem cells.

Project Manager:

Dr. Franca Fagioli
STEM CELL TRANSPLANT AND CELLULAR THERAPY CENTRE
University of Studies of Turin
Regina Margherita Hospital
Piazza Polonia, 94 – Turin

Go to the news: CLINICAL STUDY IN PHASE 1 "CLINICAL APPLICATION OF AUTOLOGOUS MESENCHYMAL STEM CELLS FOR AMYOTROPHIC LATERAL SCLEROSIS"


24/08/06 - The confirmation of the acquisition of the following machines from the Thermo Electron Corporation:

Price reserved for us 11,266.00 Euro
code 82024100: Maxi Safe 2010 1.8/ with divided work station
code 52270240: UV Lamp with timer

Price reserved for us 4,785.00 Euro
code 11177560: Centrifuge C4i
code 11175338: M4 oscillating rotor
code 11174218: Set 4 vial racks
code 11174529: Set 4 adaptors

Price reserved for us 5,258.40 Euro
code 19371: Incubator + 8 door Kit

Total order in Euro 21,309.40 + vat 20%= Euro 25,571.28.

23/03/2008 Machineries installed and tested at the Transplant Centre of 94,
Piazza Polonia – Turin (Photo 1 - Photo 2 - Photo 3)

10/01/2007:advance payment for machineries € 6,392.82
(inv. No. d/2 06 00 2508 Thermo Fisher Scientific)

15/07/2008:advance payment for machineries € 19,178.46
(inv. No. d/2 06 00 2508 Thermo Fisher Scientific)

It is possible to hypothesise, beyond the intense physical activity typical of an agonistic sport, that the increase in frequency is correlated to the use of substances assumed for the improvement in athletic performance and/or the use of pharmaceuticals for a prolonged period or in greater quantities with respect to the indicated therapeutic use. It is also assumable that there is a correlation with the specific traumas related to the game of football (for example, the headshot) or the prolonged exposure to toxins such as fertilisers and herbicides used on the football fields.

The fact that despite all of the football players examined being exposed to the same or similar environmental risk factors and only some of them contracted ALS indicates that the genetic characteristics that predispose some individuals to develop the disease probably exist. Therefore, to deepen the awareness regarding possible environmental factors and to identify the predisposed genes may provide very useful elements to identifying the origin of the disease in the 4000 Italian patients that are not professional football players.

The principal objectives are therefore, those of researching the bio-molecular characteristics that can define the increase in risk of developing ALS in professional football players and by means of these characteristics, identifying possible diagnostic indicators of the disease and possible targets for the development of new strategic therapies.

The study is pre-established to 1) investigate the clinical characteristics of Italian football players afflicted with ALS by retrospective and prospective analysis of all of the cases noted from 1970; 2) identify eventual genetic polymorphisms (polymorphisms) as possible risk factors for the development of the disease in professional football players; 3) develop cellular models obtained from peripheral tissues (e.g. primary lymphocyte and fibroblast cultures) (cellular cultures) with which it is possible to investigate mechanisms involved in the process of neurodegeneration; 4) identify by means of proteome analysis (proteome analysis) new biochemical indicators that are characteristic of the disease.

This study was created by the consolidated collaboration between Dr. Gabriele Mora of the Salvatore Maugeri Foundation in Pavia and Prof. Adriano Chiò of the Department of Neuroscience in Turin who were the authors of the survey on ALS in football players, along with the basic scientific contributions by Dr. Caterina Bendotti of the Department of Neuroscience at the "Mario Negri" Institute who has worked in this area for numerous years.

Annexes to Scholarship ("Mario Negri" Institute, Department of Neurosciences):
- Notice of Competition for 1 Scholarship for graduates in biomedical disciplines;
- Letter by Dr. Silvia Pozzi;
- Letter to Vialli and Mauro Foundation.

Annexes to Scholarship (Department of Neurosciences of Turin):
- Notice for awarding of the Scholarship;
- CV (Dr. Maura Brunetti);
- Minutes of the commission;
- Request for allocation of funds for a Scholarship (Prof. Filippo Bogetto).

The overall cost of this study amounts to 220,000 Euro and includes 3 biennial scholarships, the necessary reactants for conducting the experiment and the acquisition of an instrument (Bio-Plex System, Bio-Rad). (Bioplex)

See: Bio-Plex Suspension Array System - Specifications code No. 171000201
Bioplex specifications

For additional information on ALS, click here

Request:
Human Resources
1 biennial biology scholarship at the Mario Negri Institute (cost € 30,000)
1 biennial biology scholarship at the Maugeri Foundation (cost € 40,000)
1 biennial biology scholarship in the Department of Neuroscience in Turin
(cost € 40,000)

Material and equipment: Bio-plex System (Bio-rad): equipment for the simultaneous determination of diverse molecules of interest (cytokines, phosphoproteins, cellular death factors). Approximate cost € 72,000. Read the Press Release here

Consumption material (antibodies, enzymes, immunohistochemistry kits, culture mediums, genetic primers and isolation kits,  etc.) Approximate cost € 50,000.


07/05/ 2007: Purchased Bioplex Euro 72,000
(Bio-Rad Laboratories s.r.l., invoice No. S01/20710589 of 26/3/2007);

18/09/2007: Allocated fund for Euro 30,000 for a Scholarship at the Mario Negri Institute of Milan;

23/01/2008: Paid first request for consumables, € 9,456.00
(Link: display the invoice);

26/03/2008: Paid second request for consumables, € 20,000
(see annex: Contribution for expenses of Vialli and Mauro Foundation)

15/07/2008: Allocated fund for Euro 40,000 for a Scholarship at the Department of Neurosciences of the University of Turin

Project Managers:
This project is created by the consolidated collaboration among 3 researchers that have operated in the clinical and research areas of ALS for many years.

The High Technological Content Communicator

"If you would like to know how it feels when it is impossible to communicate, go to a meeting and pretend that you cannot talk. Use your hands but not paper and pencil because these are not used by persons with grave physical disabilities that are unable to verbally express themselves. You will be surrounded by persons that speak in front of you, behind you, around you, under you, across you and even for you, but never with you. You will be ignored to the point that you will feel as though you are an element of decor."

Mario Melazzini, afflicted with ALS

The electromyograph is an equipment that identifies, stores and process the electrical signals associated with the muscular activity of any kind and area of the human body.

Thanks to this equipment it is possible, for patients suffering from neuromuscular disorders, particularly for the Amiotrofic Lateral Sclerosis, to identify the suffering signs of the II motoneuron through the study of the peripheral nervous system and recording of the muscular electrical activity, by allowing the clinical neurologist to add an important element in reaching the certain diagnosis of the disorder. 

The disease has an average survival of about 3-4 years from the onset of the symptoms and the death occurs for respiratory insufficiency due to pneumonia, often “ab ingestis” (for ingestion of food in the respiratory tract) or to a progressive deficiency of the respiratory muscles.
According to the data of the Piedmont and Valle d’Aosta Registry for ALS, this disease has an incidence of about 2.9 cases per 100,000 inhabitants (equal to about 120 new cases every year in Piedmont and Valle d’Aosta) and a prevalence of about 7.4 cases for 100,000 inhabitants (equal to about 320 patients every year).

The cause is still unknown and there are no aetiological therapies, except for the riluzole, which has however shown its efficiency only in slowing the progression of the disease. Nevertheless, there are efficient symptomatic therapies and the possibility to assist properly the patient affected by ALS, but the patient must be fully assisted by specialised centres.

In the last years, the activity of the ALS Centre of Turin of the I Neurological Clinic of the University of Turin, managed by Prof. Roberto Mutani, and under the direction of Prof. Adriano Chiò, has grown exponentially in the quantity of work and diversification of objectives.

Since its establishment, assistance and clinical research have been its main objectives:

   • The number of scientific publications has grown constantly, with a very high and top quality productivity; in addition, the number of scientific contributions presented in the most important international as well as national conferences is very high;

   • Currently, several internal research projects are in progress, with collaborations inside the interdisciplinary research group (Turin ALS Research Group), and with external collaborations (Italian study group on ALS, EURALS, NIH and other collaborations); in particular, studies of molecular genetics and wide genomic screening; clinical and epidemiological studies (population perspective register, risk factors, such as sport, in particular football, studies on the evaluation of stress and traumas, on the weight, lipid profile); clinical studies of evaluation of the respiratory and diet parameters; psychological clinical studies on the quality of life and neuropsychological; research studies of diagnosis and prognosis markers; neurophysiologic studies); experimental clinical studies (see point d).

   • The number of outpatients and, first in Italy, treated at home with an institutionalised service of home specialist assistance, is increasingly growing, with ever more frequent admissions from outside the Region, reaching about 650 outpatient visits every year and about 200 home visits; in addition, the admissions in this structure for diagnostic and therapeutic purposes and for the execution of procedures such as the percutaneous radiological gastrostomy (proven by this group, first in the world, to be the best for patients affected by ALS) cover a large part of the assistance activity;

   • Currently, 6 therapeutic trials are in progress, two international and four domestic, of which three spontaneous studies: STEMALS multi-centre study, which evaluates the use of growth factors for the mobilisation of mesenchymal stem cells; SIRONA ONO2506PO protocol; ALALS Protocol; GOALS protocol; LITALS protocol; LAC protocol.

This quantity of work, requiring specialist training, is currently carried out by Prof. Adriano Chiò and his collaborators who constantly and specifically work on this disease, who cover non-structured working positions (2 research graduate students, 3 postgraduate students, 2 psychologists under contract, 1 scholarship biologist, some students writing a graduation thesis). It therefore seems necessary to increase the staff, structured in such a manner to ascertain the execution of the assistance activities, but also and particularly, on the research for such a devastating disease such as ALS.

The mission:
Operate as catalyser of basic, clinical, and technological research by creating the most suitable synergies to offer ALS patients increased hopes of cure and improved quality of their life.

Further details