An Innovative Approach to Develop a Better, Kinder Treatment for Children with Aggressive Brain Cancer By Cesare Spadoni

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We urgently need to find new therapies for Medulloblastoma, an aggressive form of childhood brain cancer. Too many children who develop the disease die and survivors may suffer severe health problems for the rest of their lives. We have identified a dozen drugs that show potential promise for treatment of this cancer. We are now in a position to test these in a laboratory setting with the aim of taking the most effective drug into a clinical setting within the next two years. We need your support to accelerate our research for a better, kinder treatment for this devastating childhood brain cancer.

Opens 25 May 2016 (Flexible Funding - This campaign will keep all funds raised)


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Medulloblastoma is an aggressive form of brain cancer that primarily affects children and adolescents.

Cancer is the major cause of death by diseases for children in Europe and North America. In Europe alone up to 6,000 children and adolescents die of cancer every year. It is the most serious medical problem facing the young.

Brain cancers are more frequently seen in children and Medulloblastoma is the most common type. Statistics indicate that up to 70% of children diagnosed with Medulloblastoma are still alive after five years, however this number does not tell us anything about the actual medical conditions and quality of life of the child.  For so called high-risk children (defined by the presence of specific genetic markers) their life expectancy can be as low as 30%.

This is simply not acceptable.

Current treatments for children with Medulloblastoma are outdated and harsh.

Treatment is usually a 3- step process: Surgery to remove as much tumour as possible, followed by radiation and chemotherapy. A child’s survival is dependent on many factors, including his/her age, the stage of their disease and the genetic profile of the tumour itself.

Children are particularly sensitive to the side effects of both chemotherapy and radiation.

Chemotherapy is generally based on older drugs that were approved in some cases as long ago as 40 or 50 years. These are often referred to as cytotoxic drugs. They act by specifically targeting and killing fast dividing cells like cancer cells. Unfortunately, they are unable to distinguish between the cancer cells and the normal, healthy fast-dividing cells of a developing child. For this reason, cytotoxic drugs may have serious side effects, as they also act on other fast dividing cells such as blood cells, intestinal cells and, generally speaking, on developing tissues. The considerations above hold true for radiation. Brain surgery clearly bears the risk of permanent damages to other areas of the brain.

Childhood cancer survivors are likely to suffer serious health problems later in life as a result of their cancer treatments.

Children, as developing human beings, are particularly sensitive to the side effects of current treatments and these may continue to affect them for years to come.

There is an urgent unmet need for more effective and safer drugs to treat cancer in children and provide a better quality of life for childhood cancer survivors.

The pediatric oncology community has done a great job at improving the outcome of Medulloblastoma young patients of the past 20 years, using the drugs that were made available.

However, if we want to improve further and save more children’ lives it is imperative that children with Medulloblastoma gain access to more innovative therapies that are both more effective and safer for the treatment of this aggressive brain cancer.

New generation drugs are NOT systematically evaluated for Medulloblastoma and childhood cancer in general.  

There has been significant progress in cancer research over the years. As a result, better and more targeted drugs have been developed for adult cancers. 

Sadly, children are not fully benefiting from this scientific progress. It is not profitable for the pharmaceutical industry to develop specific drugs to treat childhood cancers. Moreover, drugs used in adult are not promptly evaluated in children, even though some of these new drugs have eventually proved to be effective once they have been evaluated for treating children with cancer. 

In order to overcome this hurdle new approaches must be pursued.

Drug repurposing enables a faster,cheaper route to potential new cancer treatments.

Drug repurposing (also referred to as drug repositioning) is about looking at drugs already approved for use in one diseases and see if they can be helpful in another disease. This is not a foreign concept in medicine as many drugs were initially approved for a particular disease only to find out later that they had a therapeutic effect in other disease. The best known example is Aspirin, which was originally introduced as a treatment for pain and fever and is now widely used to prevent blood clots.

The advantage of drug repurposing is that, generally speaking, it is faster and cheaper to repurpose an existing drugs as opposed to discover and develop a completely new one. This is because approved drugs have already been characterised in many respects such as safety. Some of these drugs may even be already used in children for other diseases. Arguably, drug repurposing is a very smart approach for the identification of new agents for all those diseases that are neglected by the pharmaceutical industry.

Our campaign aims to quickly identify drug repurposing candidates as potential treatments for Medulloblastoma patients.   

We are working in collaboration with Healx, anaward-winning Cambridge-based company specialised in drug repuposing for rare and orphan disease.

Healx will apply its technology and know-how to analyse Medulloblastoma's genetic data and identify drugs that are predicted to have an effect. These drug repurposing candidates will then be evaluated in the laboratory with the aim of selecting at least one of these compounds as a candidate for clinical evaluation in Medulloblastoma patients.

The drug repurposing candidates will be experimentally tested in patient-derived Medulloblastoma cell lines, through a collaboration with contract research organisations (CROs) and academic partners. We are currently in discussion with Horizon Discovery Ltd, a drug discovery CRO based in Cambridge, UK and the Texas Children Hospital in Houston, one of the leading paediatric hospitals in the US, with strong expertise in the pre-clinical evaluation of new drugs for Medulloblastoma.

The raised funds will be precisely used to support these important preclinical experiments and all the other associated costs (e.g. purchase/ synthesis of compounds in adequate quantities, shipping etc). A small percentage of the budget will also be used to cover the costs incurred by our charity partners in setting up the campaign.

If we can proceed quickly with these experiments we will get one step closer to the possible selection of one clinical candidate to the benefit of children with Medulloblastoma.

What is Medulloblastoma?

Medulloblastoma is a form of brain cancer that is relatively more frequent in children and adolescents. As in many childhood cancers, Medulloblastoma is very often diagnosed at advanced stages of the disease. The most common symptoms include behavioural changes, headache, nausea, vomiting, as well as problems with coordination. These symptoms are largely the consequence of the location of the tumour inside the child’s brain, which is usually the cerebellum. This cancer is believed to originate from cells in the brain that fail to develop in the normal manner.

Current Treatments for Medulloblastoma more in depth

Most commonly, Surgery is the first treatment used for medulloblastoma. In addition to removing or reducing the size of the tumour, surgery can provide a tissue sample to diagnose the tumour.

Some tumours cannot be removed by surgery because of their location. These tumours are called inoperable. Even if the cancer cannot be cured, the removal of the primary brain tumour can relieve symptoms caused by the tumour pressing on the brain.

Radiation therapy is the use of high-energy x-rays or other particles to destroy tumour cells. A doctor who specializes in giving radiation therapy to treat a tumour is called a radiation oncologist. The most common type of radiation treatment is called external-beam radiation therapy, which is radiation given from a machine outside the body. 

A type of radiation therapy that may be used for Medulloblastoma is proton therapy. Proton therapy is a type of external-beam radiation therapy that uses protons rather than x-rays. At high energy, protons can destroy tumour cells. Proton therapy is becoming more widely used in the United States.

Because radiation therapy can sometimes interfere with the growth and development of a child’s brain and spine, the doctor may choose to treat the tumour differently. If radiation therapy is recommended, the approach will be based on the child’s age:

For children older than three, radiation therapy includes a moderate dose to the entire brain and spine, followed by a higher dose aimed directly at the tumour and the surrounding area or the back part of the brain.

For children younger than three, radiation therapy may be directed only to the back part of the brain or the tumour and the surrounding area after surgery and chemotherapy (see below).

Short term side effects from radiation therapy may include fatigue, mild skin reactions, vomiting, and loss of appetite. Most of these side effects go away soon after treatment is finished. Long-term side effects of radiation therapy may include problems with growth, hormone deficiencies, and problems with learning, especially higher education.

Chemotherapy is the use of drugs to destroy tumour cells, usually by stopping the tumour cells’ ability to grow and divide. 

Systemic chemotherapy gets into the bloodstream to reach tumour cells throughout the body. Common ways to give chemotherapy include an intravenous (IV) tube placed into a vein using a needle or in a pill or capsule that is swallowed (orally). In the case of Medulloblastoma it can be given directly into the cerebrospinal fluid, which is fluid that circulates around the brain and spinal cord.

A chemotherapy regime (schedule) usually consists of a specific number of cycles given over a set period of time. A patient may receive one drug at a time or combinations of different drugs at the same time.

Chemotherapeutic agents that have been found to be most effective for Medulloblstoma are cisplatin, carboplatin, cyclophosphamide, vincristine and methothrexate. All these medicines are cytotoxic drug that were originally approved 40-50 years ago.

All stakeholders and key opinion leaders agree, if we are to save more children we urgently need new treatment options for Medulloblastoma

Childhood cancer research is a neglected field as it offers little financial incentive to commercial drug developers.

Researchers acknowledge that the problem is not just a medical one but also economic. Pharmaceutical companies consider the adult population their key customer base as such, childhood cancers such as Medulloblastoma, are neglected as they are made up of a series of predominantly rare illnesses, virtually none of which offer a lucrative market for commercially developed drugs.

An important step in confronting this problem was made with the introduction of the Paediatric Medicines Regulation (or PMR) in 2007. This piece of European legislation promotes research into all children’s illnesses. However the PMR has not lived up to the promise for children with cancer

The central requirement of the Regulation is for the industry to screen every new adult product they develop for its potential paediatric use (i.e. for the treatment of children).  At the first stage of research into a drug for adults, a Paediatric Investigation Plan or PIP must be submitted to the European Medicines Agency (or EMA.) However, if the treatment being researched is for an illness that only occurs in adults, e.g. ovarian cancer, then the drug company can apply to have the Plan set aside or waived.

Drug repurposing is particularly attractive for diseases where there are no strong commercial incentives for the development of new medicines and the cost of new drug development is prohibitive for non-profit organisations and charities.

Although children’s cancers are usually different from those experienced in adulthood, advances in molecular biology have shown that there are important connections in terms of underlying biology. Indeed over the past four decades, 90% of drugs successfully given to young people with cancer have been used for different tumour types in adults.

With drug re-purposing we substantially reduce the risk failure because we are dealing with drugs already approved. For these drugs we have already solid evidence of their safety. This risk is higher with new chemical entities (NCEs) as there are totally new compounds. The potential returns are high but drug development for new compounds is an expensive and risky exercise.

It makes sense to make a relatively smaller investment in a drug repurposing project when this comes also with an increased chance of identifying a promising compound. The reason the pharma industry generally disregards drug repurposing is because, while it is possible that patented compounds are re-purposed,  more often it involves compounds that are no longer under patent protection, therefore they are not likely to generate substantial profits. Compounds that are no longer patent-protected are referred to as Generics. It is relatively cheaper to introduce a new generic compound onto the market but its commercial values is smaller. This, however, is not a barrier for medical charities as they are driven by patients’ needs rather than financial needs.

There are hundreds of ongoing drug repurposing candidates under clinical investigation. In some cases we have examples of drugs that were never used as anti-cancer drugs that have shown a potential effect against certain cancer. For instance, the anti-malarial drug Artesunate is showing promise for the treatment of colorectal cancer.



The development of better, kinder treatments for Medulloblastoma would save more children’s lives and would enhance their quality of life in the longer run.

The current treatments for Medulloblastoma in children come with severe limitations. Beside their limited efficacy, particularly on patients with aggressive forms of the disease, they also carry significant side effects.

Any new treatment that could replace or reduce the extent of radiation and chemotherapy doses is bound the benefit children in terms of quality of life, first of all.

Very few drug development programmes in the industry are carried out and there is currently no specific drug being developed for Medulloblastoma. Children with this diseases desperately need new options. Any re-purposed drug, alongside the effectiveness would bring along a level of safety.

At aPODD we are setting the example.

Drug repurposing is potentially an effective way of identifying new therapeutic agents for diseases for which there are not sufficient commercial invectives and new agent are not developed by industry. If we are successful with this project and we can identify an interesting clinical candidate for Medulloblastoma, the benefits for children with cancer will be twofold.

Not only we will have a potential new treatment for a devastating brain cancer but we would also set the example for applying the same approach and technology to investigate drug repurposing opportunities for other childhood cancers.

Not only we will have a potential new treatment for a devastating brain cancer but we would also set the example for applying the same approach and technology to investigate drug repurposing opportunities for other childhood cancers.

We are working with Healx to accelerate drug development for this aggressive childhood disease

Healx is an award-winning Cambridge-based company specialised in drug repurposing for rare and orphan diseases.  In order to identify novel repurposing opportunities, Healx combines in-depth expertise in drug discovery, computational biology and literature mining. Because of its social mission, Healx works with patient groups and charities like aPODD to help them identify safe and effective drugs.


Cesare Spadoni, PhD MBA

Cesare is a parent and a scientist that has been working in drug discovery and development since 1994. Cesare is currently Senior Director of Business Development at Auxiliis, a contract research organisation specialised in paediatric drug development. He is also advisory board member at CureAccellerator, an international platform for drug re-purposing. Cesare has extensive experience in the drug development field as he held senior business development positions at AMRI, Aptuit Laurus and ThalesNano.  Prior to this, Cesare worked as research scientist in a pharmaceutical company and in academia. Cesare holds an MSc in Applied Molecular Biology, a PhD in Neurosciences from UCL, University of London and an MBA from the Central European University, Budapest. Following the death of his daughter Laura, he became increasingly involved with childhood cancer advocacy efforts and drug development. Together with other industry professionals and experts he co-founded aPODD, an innovative non-profit organisation with the mission to accelerate the development of new medicines that are more effective and safer to treat cancer in children.

Tim Guilliams, PhD

Dr Tim Guilliams is a social entrepreneur passionate about delivering the next generation of therapeutics to patients in need. He is the Founder and Chief Executive of Healx, a Bio-Tech startup focused on drug repurposing for rare diseases by use of advanced computational methods. He is also a Founding Trustee and Chair of the Cambridge Rare Disease Network (CRDN), a charity aiming to foster dialogue and awareness around rare diseases in Cambridge.

Prior to Healx and CRDN, Tim worked with the Centre for Science and Policy on University-Industry interactions and cluster dynamics in the area of Life Sciences at the Department for Business, Innovation and Skills (BIS). He holds a PhD in the field of Biophysical Neuroscience at the University of Cambridge. As a PhD student, Tim co-founded multiple successful student societies, including the Cambridge University Science and Policy Exchange (CUSPE), where he worked closely with the Centre for Science and Policy as a Junior Associate Fellow. Before moving to Cambridge, he obtained a MEng & BEng in Bio-Engineering from the University of Brussels (VUB).

David Cavallia, PhD

David has 30 years' experience in various senior scientific and commercial roles within the pharmaceutical industry. He is currently Chief Scientific Officer at Healx and involved with a number of biotech companies at Board level. Previously he was founder and CEO of Arachnova Ltd, a company focused on therapeutic switching; previous affiliations included Glaxo Group Research Ltd and Napp Research Centre.

He is author of Modern Strategy for Pharmaceutical R&D – Towards the Virtual Research Centre, and Off-Label Prescribing: Justifying Unapproved Medicine. He is one of the first advocates of drug re-purposing, and has used this strategy to create three first-in-class developmental products to have successfully passed human proof of concept clinical stages.

David frequently contributes articles on pharmaceutical strategy and is on the editorial board of Drug Discovery Today. Formerly he was Chairman of the Society for Medicines Research. He obtained a first degree and PhD at the University of Cambridge and spent two years as a visiting Fellow at the NIMH, Washington, DC. He is author/inventor of more than 70 published papers and patents.


Selected publications, patents and books:

Drug repurposing

  • 2015 - D Brown. Antibiotic Resistance Breakers: Can repurposed drugs fill the antibiotic discovery void? Nature Reviews Drug Discovery (in press, to be published December 2015).
  • 2015 - JD Fitzgerald, D Brown. Trails of Discovery: The discovery of the phosphodiesterase-5 inhibitor sildenafil (Viagra). Dialogues in Cardiovascular Medicine. 2015 Vol 20 .No. 1
  • 2015 - D Cavalla. Off-Label Prescribing: Justifying Unapproved Medicines, Wiley-Blackwell (Book).
  • 2014 – D Cavalla. Repurposing of Espindolol for the treatment of Cachexia – final stage phase 2 clinical trials (US patent 8716325 B2).
  • 2013 - D Cavalla. Predictive methods in drug repurposing: gold mine or just a bigger haystack? Drug Discovery Today. 2013 Jun;18(11-12):523-32. doi: 10.1016/j.drudis.2012.12.009. Epub 2012 Dec 25.
  • 2012 - D Cavalla and C Singal. Retrospective clinical analysis for drug rescue: for new indications or stratified patient groups, Drug Discovery Today, 2012 Feb;17(3-4):104-9. doi: 10.1016/j.drudis.2011.09.019. Epub 2011 Oct 7.
  • 2009 - D Cavalla. APT drug R&D: the right active ingredient in the right presentation for the right therapeutic use, Nature Reviews Drug Discovery, Nature Rev Drug Disc. 2009 Nov;8(11):849-53. doi: 10.1038/nrd2981. Epub 2009 Aug 28.
  • 2008 - D Brown. The portfolio approach to successful product development in global health. Health Partnerships Review. 2008, 36-40.
  • 2007 - D Brown. Unfinished Business: target-based drug discovery. Drug Discovery Today. 2007 Dec; 12(23-24):1007-12. Epub 2007 Nov 26.
  • 2005 - D Cavalla. Therapeutic Switching: a new strategic approach to enhance R&D. IDrugs. 2005, 8(11), 914 – 918.
  • 2003 - D Brown. Rediscovering the sweet spot in drug discovery. Drug Discovery Today, 2003, Dec 1;8(23):1067-77.
  • 2002 - D Cavalla. Identification of secondary uses as a means of speeding the introduction of new products, European Pharmaceutical Review. 2002, (1), 12–18.
  • 2001 - D Cavalla. Outsourcing R&D — The value of virtuality, European Pharmaceutical Contractor, Winter. 2001, 16–18.
  • 1993 – D Brown – Repurposing of sildenafil for male impotence - Viagra (US patent 525053A).

Advanced computational biology, data analytics and literature mining

Chief Technology Officer: Dr Andreas Bender – Lecturer in Molecular Informatics at Cambridge University.

Senior Software Developer: Mr Richard Smith – Founder of Nowomics, a company using literature mining to help scientists track new research articles. Fifteen years experience building biological databases and software for biomedical research.

Technology Associates: Dr Francesco Iorio, European Bioinformatics Institute; Dr Claudio Angione, Computer Lab, Cambridge University; and Dr Krishna Bulusu, Centre for Molecular Informatics, Cambridge University.

Selected academic publications:

• F Iorio et al. A Semi-Supervised Approach for Refining Transcriptional Signatures of Drug Response and Repositioning Predictions. PLoS One. Oct 9;10(10):e0139446. doi:10.1371/journal.pone.0139446.

•2015 – C Angione, P Lio. Predictive analytics of environmental adaptability in multi-omic network models. Sci Rep. 15147. doi: 10.1038/srep15147.

•2015 – C Angione, N Pratanwanich, P Lio - A Hybrid of Metabolic Flux Analysis and Bayesian Factor Modeling for Multiomic Temporal Pathway Activation. ACS Synth Biol. Aug 21;4(8):880-9. doi: 10.1021/sb5003407. Epub 2015 Apr 27.

•2015 – K Bulusu, A Bender et al. Modelling of compound combination effects and applications to efficacy and toxicity: state-of-the-art, challenges and perspectives. Drug Discov Today doi: 10.1016/j.drudis.2015.09.003.

•2014 – AC Ravindranath, A Bender et al. Connecting Gene Expression Data from Connectivity Map and In Silico Target Predictions For Small Molecule Mechanism-of-Action Analysis. Molecular bioSystems, 11, 86 doi: 10.1039/c4mb00328d.

•2013 – F Iorio et al. Transcriptional data: a new gateway to drug repositioning? Drug Discov Today. Apr;18(7-8):350-7. doi: 10.1016/j.drudis.2012.07.014. Epub 2012 Aug 7.

•2013 – L Vegner, A Bender et al. Experimental confirmation of new drug-target interactions predicted by Drug Profile Matching. J Med Chem. 56, 8377 doi: 10.1021/jm400813y.

•2012 - RN Smith et al InterMine: a flexible data warehouse system for the integration and analysis of heterogeneous biological data. Bionformatics. 2012 Dec 1;28(23):3163-5. doi:10.1093/bioinformatics/bts577.

•2011 – A Koutsoukas, A Bender et al. From in silico target prediction to multi-target drug design: Current databases, methods and applications. Journal of Proteomics. 74, 2554 doi: 10.1016/j.jprot.2011.05.011.

•2011 – A Bender. Bayesian methods in virtual screening and chemical biology. Methods Mol Biol. 672, 175 doi: 10.1007/978-1-60761-839-3_7.

•2010 – F Iorio et al. Discovery of drug mode of action and drug repositioning from transcriptional responses. PNAS. Aug 17;107(33):14621-6. doi: 10.1073/pnas.1000138107. Epub 2010 Aug 2.




£1 or more
We appreciate your support. You will be acknowledged on the aPODD foundation website. Please help us spread the word!

£25 or more
Thank you for being a Crowdfunder and lending us your support! You’ll receive an e-certificate endorsing you as a crowdfunder and our supporter. Help us spread the word!

£50 or more
An Invitation to a webinar where you can find out more about this drug repurposing project and how this could have an impact on patients’ lives

£100 or more 
Thank you! An Invitation to a personai Skype Call with aPODD’s directors to discuss the organisation’s strategy and hear your views on the topic of childhood cancer drug development

£500 or more
You’ll be our guest at one event organised by the Cambridge Rare Disease Network

£5000 or more
You will be invited to attend the next European conference in Rome organised by Chilhood Cancer International. Registration, accommodation and meals included (travel not include).



Cesare Spadoni PhD MBA - aPODD Chairman

Tel +36 20 914 6597 (Hungary)

Twitter @apoddfoundation


Narissa Gip  - Healx

Liasion and Communication Manager

Tel  +44 7885 225 219

Twitter @healx


Cesare Spadoni
It's about a week to go before launch and we are all very excited about the way things are progressing. Alongside our project partners we are gathering support from more childhood cancer charities, which all share our goal to develop better treatments for children with cancer. Please follow us closely over the next few days. We will add more supporters to the page! Please also support us in this effort by leaving you comments and suggestions in this space. Stay tuned! Cesare
16/05/2016 21:03:18
Deborah Binner
So excited that we have now gone live with this campaign. The time for action is now. Children are dying unnecessarily because we aren't developing new drugs for them. This new model of development is driven by parents; but backed by highly experienced drug development specialists and doctors. I am so proud of this campaign and delighted to be able to contribute to it.
25/05/2016 15:37:00
Cesare Spadoni
After less than two days we have already reached 15% of the final target. I am so pleased with this start and I am very grateful for all the donations and support that have be pouring in since we launched the project. Let's keep the ball rolling!
26/05/2016 18:23:45
Graham Archer
This is a very worthy cause and a relatively small sum of money needed for it. Cancer research uk are one of the most cash rich charities in they UK I presume they have scientists looking at treatments for this terrible illness. Were they approached for funds for this and if so what was the outcome. Also will the scientists be working collaboratively as we seem to be giving and spending billions worldwide on this illness and getting nowhere, so surely a new approach is needed as the current ways if thinking are not stopping the suffering.How ill this be linked directly to patient disease outcomes?
28/05/2016 17:19:49
Cesare Spadoni
Dear Graham, many thanks for your comments. We did not specifically approach CR UK for this project, although we plan to do so shortly. Historically CR UK has been focusing on adult cancers but they are now turning their attention to childhood cancer too. So this might be the right time. We are persuaded that collaborations are essential among charities and we are actually working to this end to set up a childhood cancer drug development fund. Regarding this project we have also approached other charities. Some, such as CureSearch in the US, have agreed to support us by sharing the message. More interestingly, other charities are willing to support the later stages of the project. That's why it is very important to raise 40K now. With these funds we will be able to move quickly to the initial evaluation, knowing that there are already organisations lining up to support follow up work. Thanks for your support! Cesare
29/05/2016 08:16:28
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