THE MADDI FOUNDATION
About The Charity
The Maddi Foundation is a non profit charity which was founded by the family of a young teenage girl “Maddi” who in 2016 was diagnosed and started battling SPG15, a degenerative neuro disease, for which to date there is no cure or treatment!
The Charity aims to continue to support medical research to help cure this disease and other similar rare diseases. Conditions this rare receive very little attention and funding.
What is SPG15 ?
Onset of symptoms in SPG15 typically occurs in childhood or adolescence and the first symptom is often either leg stiffness or intellectual disability.
Neurological symptoms may include:
- learning difficulties and intellectual disability,
- structural brain malformations (e.g., thinning of the tissue that connects the left and right halves of the brain, the corpus callosum),
- loss of nerve cells in different parts of the brain,
- involuntary movements,
These issues may be progressive. Additional symptoms may include:
- numbness, tingling or pain in the arms and legs,
- problems with muscle movements and reflexes,
- issues with bladder control.
- Some individuals with SPG15 also have problems with the retina in the eye, which can cause visual impairment.
The severity of each of these symptoms is variable in affected individuals.
SPG15 is caused by mutations in the ZFYVE26 gene. It is a progressive autosomal recessive disease, which means that both parents have passed on a mutation to defect the gene. ZFYVE26 encodes the FYVE domain-containing protein ZFYVE26/SPASTIZIN, which is associated with the adaptor protein 5 (AP5) complex.
How common is Spastic Paraplegia Type 15?
The worldwide frequency of SPG15 has not been established. It is estimated that autosomal recessive hereditary spastic paraplegias occur in approximately 1 in 50,000 births. SPG15 has been reported to account for 3 to 15% of all cases of autosomal recessive hereditary spastic paraplegias.
Unfortunately, there is no cure for SPG15 at present. There is only symptom management available for example treating spasticity with medication, botox or even surgery for lengthening tight muscles.
If Juvenille Parkinsons is a symptom therefore it can be treated sometimes with a shorterm medication such as levodopa however once this has built up in the system it becomes less effective. Exercise and physio is also a key to keeping muscles stronger before they atrophy as at this stage it becomes more difficult to gain muscle strength again.
SITraN (Funded by The Maddi Foundation)
The Maddi Foundation and Save Our Maddi are engaged with Professor Mimoun Azzouz previously Head of Neurobiology at Oxford Biomedica and one of the leading experts in the UK in the use of gene therapy for neurodegenerative diseases. He leads an extensive programme at the Sheffield Institute for Translational Neuroscience (SITraN) aiming to replace or silence faulty genes in forms of neurodegenerative diseases which are caused by a known gene mutation.
Gene therapy technology is currently generating great optimism among patients and their families. However, to develop gene-based therapy for SPG15, further extensive studies are needed to refine our strategy before entering clinical application.
Funds are needed to achieve the following aims:
1) Prepare the therapeutic virus for testing in cells and model systems in the lab to generate a proof-of-concept, a critical step before initiating further pre-clinical work;
2) Prepare the therapeutic virus carrier at the quality acceptable for clinical use in humans;
3) Determine the minimal dose of the carrier that generates efficacy in our animal model;
4) Assess potential adverse effects in a regulatory safety study.
5) Secure the licensing needed to initiate human clinical trials.
Cambridge Institute for Medical Research
Dr Jennifer Hirst: I am a researcher at the Cambridge Institute for Medical Research in the laboratory of Professor Margaret Robinson. My field of speciality is ‘cell biology’, with an aim to understand how cells work, and then we can try to understand what happens in disease when cells fail to work.
My focus is understanding the protein machineries that is used by cells to sort cargo proteins for transport to one of a number of destinations. One of these sorting machineries is called AP-5 and involves six proteins working together in a complex – these proteins are the products of the genes SPG15, SPG11, AP5Z1, AP5B1, AP5M1 and AP5S1. My aim is to further understand why faulty versions of SPG11, SPG15 or AP5Z1 have damaging effects on the survival of nerve cells and lead to the rare neurodegenerative disorder hereditary spastic paraplegia.
Chair of Translational Neuroscience, ERC Advanced Investigator, Director of Research and Innovation - University of Sheffield Department of Neuroscience.
Professor Azzouz has a long standing interest in developing gene therapy approaches for neurodegenerative diseases His research focuses on new therapeutic strategies for monogenic neuromuscular disorders and other motor neuron diseases.
Doctor Jennifer Hirst
Principal Research Associate, Robinson Labs, Cambridge Institute for Medical ResearchJenny is a cell biologist who had previously discovered the AP4 and AP5 adaptor complexes and has been studying their function and link with Hereditary Spastic Paraplegia.
Professor Giovanni Stevanin
Institut du Cerveau et de la Moelle Epinière (Brain and Spine Institute), ParisGiovanni Stevanin is Professor of Neurogenetics at the EPHE/PSL Research University and Research Director at the Institut du Cerveau et de la Moelle Epinière (Brain and Spine Institute, Paris, France). He (and his students) identified 10 genes leading to hereditary spastic paraplegias, among them SPG11 and SPG15. He is co-coordinating the international network on these diseases, SPATAX, and develops projects towards therapeutic approaches on them.
Dr Andrew Grierson
Sheffield Institute for Translational Neuroscience University of Sheffield, UKI am a principal investigator based at the University of Sheffield. In my lab we are interested in identifying mechanisms underlying neurodegenerative disease and designing therapies that target these mechanisms. We use cell and neuronal cultures as well as zebrafish and mouse in vivo models. In relation to HSP research, we developed a mutant spastin mouse model that develops a progressive spastic gait associated with defective axonal transport and hallmark axonal swelling pathology. Zebrafish are an ideal model to generate stable genetic models of rare human disease, including HSP. We have recently developed a zebrafish HSP model carrying a spastin mutation that develops a motor phenotype.
Professor John Fink
Professor in the Department of Neurology and Director of Neurogentic Disorders Program at the University of Michigan.
Dr Craig Blackstone
Senior Investigator, Cell biology section at the National Institute of Neurological disorders and strokes.
Dr Evan Reid
Medical Genetics and Principal Investigator, Cambridge Institute of medical research
Professor Henry Houlden
Professor of Neurology, Faculty of Brain sciences, National Hospital of Neurology, Queens Square, LondonProfessor Houlden runs a research group that are interested in ALL Neurogenetics. Seeing Hereditary Spastic Paraplegia patients is a main interest to Henry.
Professor Jürgen Winkler, M.D
(Professor of Neurology and Head) University Hospital Erlangen, GermanyScientific leadership
- Bavarian Research Network “Induced Pluripotent Stem Cells (For IPS)”, Speaker
- Speaker of the Department of Neurosciences, University Hospital Erlangen
- Scientific advisor for the German Bundestag with focus on stem cell technology
Main focus of research
- Clinical Neurosciences
- Head of Movement Disorder Center (i.e. Parkinson disease, Huntington disease, hereditary spastic paraplegia)
- Neurogenetics or rare neurological
Professor Dr Stephan Klebe
University Hospital Essen, GermanyResearch interests
Movement Disorders, Hereditary Spastic Paraplegia, Neurogenetics
Executive senior consultant and lecturer Dept. of Neurology at University Hospital of Essen, Germany
Dr. Thomas Bourinaris MD MSc
University College London Hospital, UKIn 2017, I joined the team at the UCL Institute of Neurology, Queen Square in London and started a PhD clinical research fellowship under the supervision of Professors Houlden and Hardy. My main research interests include the genetics and pathophysiology of hereditary spastic paraplegias, Parkinson’s disease and other movement disorders. For my research purposes, I’m planning to employ a combination of clinical and research data, including analysing results of genetic studies, such as whole exome and genome sequencing data, as well as functional studies and experimental models.
Dr Channa Hewamadduma
Consultant Neurologist and Senior Lecturer at Sheffield UniversityDr Channa Hewamadduma is dedicated to improving the trial-readiness of HSP patients. His team is in investigation for biomarkers and molecular causes of HSP. He runs a regional HSP clinic at the Royal Hallamshire Hospital, Sheffield’s Teaching Hospital’s Trust.
University Hospital Würzburg, GermanyDept of Neurology, Developmental Neurobiology (Head: Prof. Dr. Rudolf Martini), University Hospital Würzburg.
Since Aug’ 2018 Doctoral student in the laboratory of Prof. Dr. Rudolf Martini in Neuroscience, Developmental Neurobiology, Department of Neurology.
Research interests – Secondary neuroinflammation as disease amplifier in genetically-mediated diseases of the central and peripheral nervous system.
Founder, CEO & Maddi’s MumI am proud to be Maddi’s mum and I set up The Maddi Foundation after Maddi was diagnosed with SPG15.There is no other charity out there funding research for a cure into Spastic Paraplegia Gene 15. I realised that our only hope was to start one ourselves to help raise the profile and awareness into this rare disease.I gave up working in the florist industry to set up The Maddi Foundation with my other daughter Alexandra.
Co Founder, Trustee & Maddi’s sisterAlex, Maddi’s sister, is Co Founder of the charity and has worked hard alongside her mum in fundraising and campaigning since Maddi was diagnosed with SPG15. Having supported Maddi through the toughest of times since her diagnosis, Alex is keen to raise awareness of the Maddi Foundation to help both her sister and all others that suffer with Spastic Paraplegia types. Alex works within the business advisory and insolvency industry.
TrusteeThe Maddi Foundation means a lot to me as my son grew up with Maddi and I was so shocked when she was diagnosed with such a rare disease that had no answers or no cure. After seeing the impact it had on Maddis family, I wanted to help them raise awareness and fundraise into research for a cure for SPG15. I was delighted to be asked to join the team in a fundraising support role and feel honoured to be part of the special charity.
Trustee & Maddi’s BrotherHarry – Maddi’s brother who decided to become a Trustee for The Maddi Foundation having watched his little sister go through a very tough time with the disease. I have been involved in raising awareness and fundraising since she was diagnosed.
I am the director of an electrical company based in Essex, UK.
Glen Murphy MBE
Glen – is an English actor, producer and sports therapist. Best known for his role as firefighter George Green in Londons Burning. He was awarded an MBE in 2007 for his charity work and also qualified as a sports therapist in 2014, he has clinics based in Essex and Italy.
Having knowing Maddi and her family for quite sometime he has watched the progression in the disease and was inspired by Maddi’s courage and determination of fighting SPG15 he felt privileged to be asked to come on board as a trustee.