4-year-old Irai will be the first Spanish patient to receive gene therapy treatment to cure her rare disease which prevents her from moving and talking. The Columbus Foundation has pioneered a revolutionary project in Europe which will treat children with rare neurodegenerative diseases, the first of which is the aromatic amino acid decarboxylase (AADC) deficiency. Since the success of the clinical trials in the USA carried out by the organization in collaboration with the Ohio State University and UCSF, the first cases are already being treated in Varsovia. This includes little Irai who is scheduled to have the operation on the 14th of May.
Irai has a rare disease that only affects 130 children worldwide, it is the aromatic amino acid decarboxylase (AADC) deficiency, also known as childhood Parkinson. It is a genetic neurological disorder that affects the brains’ ability to produce neurotransmitters, specifically dopamine and serotonin, the most crucial ones for daily life. ‘The lack of this protein results in a disconnection between the brain and her body, with all of the consequences this has’, noted the president of the Columbus Foundation Damià Tormo.
The Foundations mission is to promote the access of therapies that are more advanced and effective to those who need it the most. With the operation of Irai, the foundation will continue with gene therapy to treat rare diseases, a process that began in 2017 in the US with the first clinical trials to cure AADC deficiency. This project has already succeeded in providing significant improvements in the quality of life of its patients. It is truly a revolutionary development in the medical field. Currently, six patients have been treated in the University of California in San Francisco and two patients in the Interventional Neurotherapy Centre in Brodno, Poland.
Irai, the first patient who will receive treatment
Irai has the most beautiful smile and has been a tireless fighter since she was born. She is now four years old and she is still incapable of holding her head upright. She can’t sit down, hold her head or use her arms nor legs. She can’t speak and she frequently suffers from painful episodes of neck tension linked with the diversion of her eyes, called oculogyric crises. However, all of this doesn’t prevent her from communicating with her family through her gestures day after day.
‘For us, the fact that she has been able to take part in the study has been like winning the lottery. It hasn’t been a family decision but a medical one’. This was said by her father, Alex Casadessús, who has been accompanying Irai alongside his wife and other two children on the journey towards a cure. ‘After almost four years of investing so much time and money in different therapies with scarce results, we are finally living what is happening now with so much excitement. The hope that Irai will one day be autonomous is due to this therapy’ he comments with a certain nervousness and excitement with respect to the imminent operation.
Gene therapy: replacing the missing gene
Gene therapy is a type of treatment that uses genes to treat or prevent diseases, allowing the insertion of a gene into the cells of a patient instead of having to medicate or operate in order to treat the disorder. ‘The therapy aims to return to these children the information that they were missing when they were born’ points out Tormo.
To achieve this, the Columbus Foundation entrusts a multidisciplinary team managed by the Dr. Krystof Bankiewicz, a gene therapy specialist and resident professor of neurological surgery in the University of California in San Francisco (UCSF). ‘The objective of our intervention is to restore the function of this defective gene via direct inoculation of a modified virus (viral vector) into the brain that will provide the correct and functional copy of the enzyme necessary for the synthesis and processing of these key proteins. The new gene is administered surgically by means of a technique guided by Nuclear Magnetic Resonance in the area of the brain where the gene is physiologically expressed.’
Results after the operation
‘After the therapy, little by little, as the neurological circuits start to connect, Irai should start to hold her head upright, sit down by herself, start hold things in her hands, speak, crawl and in time walk…’, comments Alex.
However, of course, each child develops differently after the therapy and at different speeds. The medical team awaits important results: ‘Today, after the surgery, every patient has developed control over their head, improved muscle tone, certain ability of spontaneous movement and disappearance or dramatic decrease in the oculogyric crises. Every one of them has shown an improvement in sleep, their moods (they are no longer as irritable), and their respiratory problems. So far, the patient that has seen the most improvement has been one that is now able to eat solid food, sitting up without any help, and is learning how to walk and has even started to say their first words’, describes Bankiewicz, one of the doctors that will be present during Irai’s intervention on Tuesday 14th of May in Varsovia.
‘We may be possibly speaking about a few months or even years of recovery. However, what is really important is that we start to see significant advances in her development’, concludes the father of the girl.
Kilometres for Irai
Irai’s case is one of many that the Foundation wants to support. All of this activity is totally altruistic and with a reduced cost. The doctors donate their time, the therapy and the procedure. Apart from that, though it is very difficult to estimate, the actual cost would be far above 500,000 euros per patient. ‘The objective of the Columbus Foundation is to ensure that none of the children are left without receiving the treatment. We have the doctors, the technology, the man power… now all we need is that the lack of economic interest for these treatments (due to the cost) doesn’t prevent the access for those that need this help the most’ comments the Foundations President.
With this in mind, the organization has started the initiative #kilómetrosparaIrai, that aims at raising funds that will finance the gene therapy and the costs associated with children with rare diseases. For this, in the home page of the website, there is a space for donations that invites the people to buy kilometres that will shorten the distance to Varsovia, the city where they will be treated.
GM1 gangliosidosis type 1, Niewmann-Pick A and Niewmann-Pick C
Initially, the foundation’s project will be centred around four rare diseases: Deficiency of AADC, GM1 gangliosidosis type 1, Niewmann-Pick A and Niewmann-Pick C. To achieve this, it works with the best institutions and experts in this field, collaborating with the American team of neurologists and neurosurgeons so as to provide the best doctors necessary for the development of these therapies.