"Genetically modifying neurons to improve transplants could mean a revolution in therapeutics"
Aim: Gemma is our primary PI and a renowned Spanish geneticist and professor at the University of Barcelona. She specialises in human genetics, particularly in the study of inherited diseases and molecular genetics.
Contribution: Gemma has counseled us on using neurons for therapeutic purposes, guiding us to focus on stroke and cellular therapy. Her insights into genetic engineering helped us incorporate LoxP sites and improve transcription.
Conclusions: We’ll focus on cellular therapies using an AAV backbone and LoxP sites to remove the reporter cassette.

"iPSC derived NPC are safe and reliable for patients, and hold great promise for future therapeutics"
Aim: Daniel is an experienced researcher in neuroscience and group leader at the Institute of Neurosciences and IDIBAPS.
Contribution: He recommended using NPCs instead of neurons, emphasizing their benefit in generating glial cells. His insights also led us to adopt AAVs for safe transfection and implement a GCamp expressing line of It-NES cells.
Conclusions: We’ll use GCamP expressing It-NES cells to culture NPCs for neural experiments, with AAV transfection.

"You need to ensure that the probability of teratoma formation is zero"
Aim: Manuel is an expert in cell preservation and handling with a focus on improving safety measures for clinical applications.
Contribution: He advised us on cryopreserving our cell cultures and ensuring immunocompatibility, suggesting mesenchymal stem cells to prevent rejection and using flow cytometry for selecting differentiated cells.
Conclusions: We’ll consider new commercial media to improve cell viability and ensure no teratoma formation through proper cell selection.

"The interesting thing would be to have the KOs independently, and then their combinations"
Aim: Arístides is a postdoctoral researcher specialising in advanced therapies and rare genetic diseases at the Institut de Recerca Sant Joan de Déu.
Contribution: He explained methods for gene knockout using CRISPR Cas9, focusing on multiple guide RNAs and culturing techniques for selecting KO cells.
Conclusions: We’ll implement these methods for efficient gene knockout and KO cell selection.

Aim: Ferran is a bioinformatics professor at Universitat de Barcelona and researcher in human molecular genetics.
Contribution: He introduced us to bioinformatic tools like UCSC Genome Browser and helped us find human genomic sequences needed for our project.
Conclusions: We’ll use the tools he recommended to find sequences for our constructs.

"In in-vitro NPCs, AAVs are incorporated depending on the capsid"
Aim: Albert is a team leader focused on Huntington’s disease research and BDNF administration challenges.
Contribution: He highlighted challenges with BDNF’s BBB crossing and the need to differentiate between its mature and pro forms for effective neuron survival.
Conclusions: We’ll modify our design to deliver mature BDNF only, ensuring therapeutic effectiveness.

"Publishing is the currency of academia, but it can undermine tech transfer by limiting IP opportunities essential for commercialization."
Aim: The Fundació Bosch i Gimpera helps connect universities with companies to transfer innovation to society and manage intellectual property.
Contribution: They advised us on the process of patenting and tech transfer. They highlighted the need to decide if patenting is worth it, balancing between publishing and commercial opportunities. They also guided us through UB’s policy on patent costs and management.
Conclusions: We need to complete the invention form to start the patent process and gather feedback from pharmaceutical companies about potential interest in our therapy.

"You need to clearly define your product before carrying on"
Aim: Creatio is an academic center focused on the production and validation of advanced therapies, working with the University of Barcelona to promote innovation.
Contribution: They emphasized the importance of clearly defining our product and its mechanism of action. They also recommended selecting the least invasive administration route and ensuring safety through proper animal testing.
Conclusions: We will characterize our therapy thoroughly to enhance its therapeutic effect and ensure compliance with regulatory standards.

Plan everything carefully and keep in mind your available time: what information do we need to gather? What resources do we have available?
Aim: Ana is one of our secondary PIs and an associate professor at Universitat de Barcelona. She has worked with iPSCs and CRISPR/CAS-9, amongst other techniques.
Contribution: Ana helped us review and determine the necessary experiments we could do for proof of concept 2. As our team’s PI, she has helped us troubleshoot on cloning-related lab activities, and define the workflow we would be following for proof of concept two.
Conclusions: We need to sequence our constructs and DNA fragments to verify data is correct. qPCRs assays should be used to determine expression activity of BDNF by our different constructs.

The more genetic modifications the more it affects cell viability
Aim:Aristides is doing post-doctoral research in new advanced therapies and rare genetic diseases at the Institut de Recerca Sant Joan de Déu. We contacted him to understand how to implement CRISPR modifications to our therapeutic product.
Contribution: Arístides discussed the implications of gene editing on cellular viability, highlighting that while some gene knockouts could be lethal, others may not significantly affect cell function. This indicates the need for a systematic approach to test individual and combinatorial gene knockouts to assess their effects on cellular behaviour, which is key in establishing a proof of concept for clinical applications.
Conclusions: Discussed the implications of gene editing on cellular viability.

Once we have the proof of concept, we improve it and adapt it
Aim: Manuel Reina is an expert in cell preservation and handling, with a focus on improving safety measures and optimising the process of cell transfection for clinical applications.
Contribution: Manuel suggested beginning with AAV for initial animal trials and then transitioning to lentivirus (LV) once safety is verified, to establish a stable cell line and develop a higher-quality product. He also emphasised the need to handle hundreds of millions of cells, carefully quantifying dosage while considering scalability. However, upon considering safety measures, he also found it adequate to infect the cells with an AAV during the priming stage (after thawing and before the transplant).
Conclusions: Manuel suggests a phased strategy starting with AAV trials while infecting the cells during the priming stage for a more efficient development.

You need to find out the accurate timing to administer BDNF, the first 6 hours are crucial
Aim: Albert is Team Leader of a research group focused on Huntington’s disease. He has already worked with BDNF which is why we wanted to talk with him about its limitations.
Contribution: For experiments, a 3D-printed model could simulate hypoxia on one side of a neural plate, though we are considering more practical setups. It is crucial to establish the right timing and dose of BDNF administration, particularly within the first six hours post-injury. A triculture system, consisting of neurons, astrocytes, and microglia, could be used to model stroke conditions and evaluate whether BDNF-modified neurons can be rescued from hypoxia-induced cell death.
Conclusions: We could use a 3D model or a triculture system in order to test our product.

The fact that neuroprotectors can be added to revascularization is very promising
Aim: Xabi Urra is a neurologist and researcher focused on stroke treatment and neuroprotection. He works at Hospital Clínic in Barcelona and has made significant contributions to stroke management and immune response studies.
Contribution: Xabi Urra, from the Stroke Unit at Hospital Clínic, explained the urgency of stroke treatment, as time is a critical factor in preventing irreversible brain damage. He highlighted the importance of new technologies in expanding the range of patients who can benefit from thrombectomies and other treatments. He also noted that, although neuroprotectors have failed so far, new technologies could change this outcome. Furthermore, he deemed it feasible to apply neuroprotectors in combination with revascularization treatments.
Conclusions: The proposal to combine neuroprotectors with revascularization presents a promising opportunity, although there hasn’t been much research in this field.

It's the first time someone from the lab has contacted me to talk about these things. This is exactly what needs to be done
Aim: Míriam has worked at Hospital Arnau de Lleida for 30 years, assisting with rehabilitation. Nowadays, she helps patients during the first days post-stroke.
Contribution: Míriam San José, an occupational therapist at Hospital Arnau de Lleida, emphasises the importance of integrating lab therapies with the practical rehabilitation of stroke patients. She highlights that latent neurons have the potential to recover, reaffirming the relevance of early and consistent intervention. She also stresses that the recovery of executive functions, such as hand movement and speech, is faster when sensory stimulation begins early. Coordination between the medical team and family involvement is crucial for successful rehabilitation.
Conclusions: The project’s approach is appropriate as it combines therapy with functional rehabilitation, allowing for early intervention. This integration could significantly improve outcomes for stroke patients.

Gaining speed allows for significant improvements by reducing response time and catheterization
Aim: Toni Garcia is a doctor based in Agramunt, a rural town near Lleida. We reached out to him to gain insight into the challenges of healthcare in smaller hospitals, which often have fewer resources compared to the larger facilities in Barcelona.
Contribution: Toni Garcia highlighted the limitations faced in treating stroke patients in rural settings, where they often lack the same tools available in larger hospitals. He emphasised the need to improve communication between ambulance technicians and doctors to avoid errors in identifying stroke. Additionally, he expressed that the possibility of regenerating brain tissue, as proposed by the project, would be a revolutionary advancement in managing these injuries. Toni also mentioned that, despite the challenges, most patients show a high acceptance of new therapies.
Conclusions: By increasing the therapeutic window we can make our therapy more accessible to rural zones, where patients demonstrate strong receptiveness to innovative therapies.

It is very important to check the viability post-thawing to avoid introducing too many dead cells
Aim: María is Head of the Stroke Unit of the Hospital La Paz, from Madrid. This unit has been operative for more than 20 years and has attended more than 1.200 patients.
Contribution: Maria Gutiérrez highlighted the significance of viability in stem cell treatments for stroke patients, emphasising the importance of minimising cell death. She explained that their therapy is designed to be an adjunct treatment, benefiting both patients who have received standard therapies like TPA and those who haven't. Gutiérrez discussed the necessity of animal models to test their approaches and stated that they should administer treatments within 24 hours of a stroke event. She also shared insights on the most effective administration routes for stem cells, noting that intravenous methods yield good recovery results without the invasiveness of intracerebral approaches.
Conclusions: Enhancing the understanding of administration routes and optimising the timing of treatments could significantly impact patient outcomes.

You should perform a compatibility test before applying the cells, even though they are universalized
Aim: Marc is the Head of the Stroke Research team at the Hospital of Vall d’Hebron Institute, he has also worked in stroke research and has been awarded by the Spanish Neurology Society.
Contribution: Marc Ribó emphasised the need for compatibility testing before administering stem cells, despite their universalized nature. He discussed the importance of selecting a homogeneous patient population for clinical trials, ensuring that candidates are neither too well nor too ill to avoid the effects of ceiling and floor effects on treatment outcomes. Ribó highlighted that treatment should ideally be administered before significant lesion establishment occurs, ideally within the first week post-stroke. He pointed out that intra-arterial administration appears to be the most feasible route, although logistical challenges remain a concern.
Conclusions: Discussions with Ribó highlight the need for thorough preclinical testing and a well-defined clinical trial strategy for stem cell therapies in stroke. Optimising administration methods and ensuring compatibility are key to future trial success.

The neuroprotective and neuroregenerative aspect is essential and is underdeveloped
Aim: Pere Cardona is the director of the Neurovascular program and Stroke Unit of the Hospital Universitari de Bellvitge (HUB).
Contribution:In this meeting, Pere Cardona highlighted the significant progress made in reducing stroke mortality, but noted that about 15% of patients still experience severe sequelae. He emphasised the importance of combining therapies, such as Aptatoll with thrombectomy, and suggested using software like RAPID to accurately select patients based on risk regions. Cardona also discussed the logistics and safety considerations of using AAV for gene delivery and the challenges of administration routes, particularly after thrombectomy. He stressed the need for further research in neuroprotective and regenerative therapies.
Conclusions: Pere mentioned the need for research in this field and showed us really useful tools to successfully implement our therapy and ensure its seamless integration within the hospital’s workflow (RAPID).

From a clinical point of view, the approach of two-week administration favours us
Aim: Ariadna Mas is the General Deputy Director of Health Planning and Dr. Sònia Abilleira is the Director for the Strategic Plan for Cerebrovascular Diseases. They both work at CatSalut, the Catalan Service of Health.
Contribution: The attendees emphasised that the proposed therapy aligns with a controlled situation within a two-week window post-stroke, suggesting it could enhance treatment efficacy. They noted that while the therapy is not currently available, its timing within the acute phase could make it a strong candidate for clinical application. This reinforces the need for rigorous testing and validation of the therapy within the proposed time frame.
Conclusions: Timing within the therapeutic window is critical for efficacy.

Your therapy could be applied to a much broader group of people than it currently does
Aim: Joaquin Antonio Delgadillo is the head of regulatory affairs at the Catalan Blood and Tissue Bank, a public entity responsible for ensuring the supply of blood and tissue in Catalonia. We reached out to him for his expertise in regulation law and managing cell banks.
Contribution: Joaquin talked to us about the use of viral vectors such as AAV for the initial essays and lentivirus for a most stable cell line. He also proposes to start with plasmids in order to ensure we know the appropriate dose and emphasises the need to keep in mind all the regulations.
Conclusions: He highlights the timing of application post-stroke, suggesting that early intervention (ideally four days post-event) could enhance recovery outcomes.

We should perform the treatment on animals within 24 hours
Aim: María is Head of the Stroke Unit of the Hospital La Paz, from Madrid. This unit has been operative for more than 20 years and has attended more than 1.200 patients.
Contribution: She detailed the various animal models used for studying cerebral infarction: the middle cerebral artery model leaves maximum deficits in ischaemic patients, the craniotomy with nine zero suture can work for both transitory and permanent ischaemia, and the intraluminal filament model only for transient ischaemia. She also noted the necessity of evaluating neuroprotective treatments in these models.
Conclusions: Our best option to test on mice is the craniotomy with nine zero suture, which should help us evaluate the neuroprotective treatments.

Neuroprotectors have failed so far, but with new technologies, the outcome of future clinical trials could be different
Aim:Xabi Urra is a neurologist and researcher focused on stroke treatment and neuroprotection. He works at Hospital Clínic in Barcelona and has made significant contributions to stroke management and immune response studies.
Contribution: Xabi emphasised the historical failures of neuroprotectors and the necessity of clinical testing to validate their efficacy. He suggested a possible change in outcomes due to new technological advancements in conjunction with revascularization methods.
Conclusions: Combining neuroregenerative therapies with new revascularization techniques shows promise for improving patient outcomes.

We need to ensure that our line has only two copies of the gene of interest.
Aim: Aristides is doing post-doctoral research in new advanced therapies and rare genetic diseases at the Institut de Recerca Sant Joan de Déu. We contacted him to understand how to implement CRISPR modifications to our therapeutic product.
Contribution: Arístides underscored the necessity of extensive genomic characterization to prevent unwanted off-target effects and ensure the stability of the modified cell lines. He stressed that understanding the chromosomal makeup of the cells is crucial to avoid complications during later stages of research and application. This highlights the importance of rigorous testing in the transition from laboratory to clinical settings.
Conclusions: Underscored the necessity of extensive genomic characterization; it is crucial to understand the chromosomal makeup of the cells.

We should quantify the dose and keep in mind the scale
Aim: Manuel Reina is an expert in cell preservation and handling, with a focus on improving safety measures and optimising the process of cell transfection for clinical applications.
Contribution: Manuel recommended using AAV vectors in early-stage animal testing to confirm safety. Once safety is established, lentiviral vectors (LV) would be used to create a stable cell line for better clinical results. He suggested optimising and adapting the product as the proof of concept is proven.
Conclusions: Using AAV vectors may be enough to confirm safety for the POC.

It is fundamental to gain recognition in order to sell your product from the beginning
Aim: Sonia Macià is Executive Medical Director at LAVA Therapeutics, working on early development with several immunotherapies for solid and hematologic malignancies.
Contribution: Sonia noticed that our budget needed modifications, she talked to us about CETIS and recommended us to develop clinical phase 1 with expansion and ask for an ODD validation. We agreed on intracerebral injection, although we could combine it with intravenous. The drawbacks she mentioned were the need of neurosurgeons and operating rooms, making it difficult for all hospitals to implement our therapy, which could make it less attractive to big pharma.
Conclusions: We should do clinical phase 1 with expansion.

Animal models also have their limitations, so it’s complicated
Aim: Sol Ruiz is a representative of the Spanish Agency of Medicines and Medical Devices (AEMPS), which ensures the security, quality and effectiveness of medications in Spain.
Contribution: Sol emphasised the importance of justifying why the proposed therapies, such as the use of iPSCs, would offer something superior to standard therapies or to previous treatments that did not achieve the expected efficacy, such as developments for Parkinson's. She also highlighted the need for thorough in vitro testing before moving to in vivo studies, given the limitations of animal models, and stressed the relevance of clinical trials controlled by European regulations to ensure the product's safety and efficacy.
Conclusions: We need to justify the superiority of therapies like iPSCs over standard treatments, she also stressed the importance of thorough in vitro testing before in vivo studies, while complying with all the european regulations.

You have to choose the right population for your clinical assay
Aim: Marc is the Head of the Stroke Research team at the Hospital of Vall d’Hebron Institute, he has also worked in stroke research and has been awarded by the Spanish Neurology Society.
Contribution: He emphasises the necessity of conducting compatibility tests prior to cell therapy administration, ensuring patient safety. His experience with clinical trials informs our approach to selecting suitable patient populations for reliable results. Additionally, his focus on timely interventions and optimising treatment administration routes enhances our understanding of the logistical challenges inherent in clinical testing for stroke therapies.
Conclusions: Emphasises the critical need for compatibility testing and careful patient selection in clinical trials to ensure safety and efficacy.

[Animal testing] is inevitable for the sake of humans
Aim: We have chosen to include the patient’s opinions on animal and clinical testing because our goal is to make their experience as comfortable as possible.
Contribution: The majority of patients had mixed feelings with animal testing, although they did admit it was necessary. We noticed different attitudes depending on what was the tested animal: while rats were almost always fine, dogs and primates were often unacceptable. On the other hand, clinical testing was largely supported. However, some patients were concerned about the uncertainty, the placebos, and the secondary effects.
Conclusions: The patients can be reluctant to animal testing but all of them agree on its importance to medical development.

We have detected the following potential risks: contamination of stem cells and exposure to LV
Aim: Judit Regidor, Jose Ramon Gumiel and Judit Monlleó work at the Occupational health and safety unit, and Environment unit of OSSMA. OSSMA is the Security, Health and Environment Office of the University of Barcelona, and it helps to prevent laboral risks and damages to the environment.
Contribution: The discussion emphasised identifying specific risks in clinical applications, such as contamination and accidental release of GMOs. They detailed necessary protocols for managing spills and the importance of using appropriate disinfectants. They also mentioned the correct way to transport GMOs and the importance of the double security system. These insights are essential for developing robust clinical testing procedures that prioritise the safety of patients and researchers.
Conclusions: They helped us identify and mitigate clinical risks regarding spills, contamination and transport procedures.

Pluripotent cells have an amazing future, and we are just learning how to handle them
Aim: Pilar Azcárrega is the General Director of Public Health, Quality and Innovation and Cristina Guijarro is a medical inspector; they both work at the Spanish Ministry of Health, which ensures equity and quality health services in Spain.
Contribution: The officials from the Spanish Ministry of Health provided valuable insights into the current state of stroke care in Spain, highlighting the need for both improved management practices and innovative treatments. They expressed interest in our project, emphasising the importance of addressing systemic barriers and regulatory challenges to facilitate the introduction of new therapies into the healthcare system.
Conclusions: They see potential in pluripotent cells for stroke therapy but emphasise the regulatory and systemic challenges to integrating such innovations.

This therapy should be applied in specialised centres
Aim: Ariadna Mas is the General Deputy Director of Health Planning and Dr. Soria Abilleira is the Director for the Strategic Plan for Cerebrovascular Diseases. They both work at CatSalut, the Catalan Service of Health.
Contribution: The discussion reveals that introducing this therapy involves multiple stages, including generating solid clinical evidence, securing funding from the healthcare system, and navigating the regulatory landscape to ensure compliance with established guidelines. Understanding these elements is vital for the therapy’s successful adoption.
Conclusions: They validated our approach and helped us realise that regulatory compliance and funding are essential for therapy integration.

You need to consider what the safety concerns might be if those cells remain in the brain
Aim: Sol Ruiz is a representative of the Spanish Agency of Medicines and Medical Devices (AEMPS), which ensures the security, quality and effectiveness of medications in Spain.
Contribution: Sol explained that all advanced therapies, such as those based on IPS cells, are subject to strict controls at both the European and national levels. She detailed the regulatory process a drug must follow, from preclinical trials in certified laboratories to marketing authorization by the European Medicines Agency. Additionally, she emphasised the importance of meeting safety standards during clinical development, with requirements adjusted according to the specific type of product.
Conclusions: We gained insight about the regulatory pathway for drugs that our product, as an advanced therapy, must comply with. These include preclinical trials in certified labs and marketing authorization by the European Medicines Agency,

Advanced therapies are medications, but they are not like ibuprofen
Aim: Joaquin Antonio Delgadillo is the head of regulatory affairs at the Catalan Blood and Tissue Bank, a public entity responsible for ensuring the supply of blood and tissue in Catalonia. We reached out to him for his expertise in regulation law and managing cell banks.
Contribution: The meeting clarified that our therapy is classified as an “advanced therapy medicinal product” (ATMP), subject to strict regulatory requirements. Compliance with gene-modified cell therapy regulations is essential, ensuring that both cell lines and viral vectors meet approved manufacturing standards. Preclinical tests and clinical trials must gain approval from regulatory agencies. Additionally, authorised drug manufacturing facilities are required, with emphasis on the stability and efficacy of the cells during storage. New European regulations, including the SOJO framework, will further impose strict guidelines for human-origin substances.
Conclusions: Our product, labelled as “ATMP” must align with strict European regulations for advanced therapies, focusing on safety and efficacy. Ensuring compliance throughout manufacturing and clinical trials is essential for successful implementation.

This is the first time such a young team reaches us
Aim: Valentina Cordo works at the European Medicine Agency (EMA) and she is also working on the application of stem cell therapy and modified cells for neurological recovery, particularly in stroke patients.
Contribution: Valentina noted that the EMA provides a scientific recommendation to the European Council (EuCo) for a given therapy, however, it is the EuCo who has the final say on whether or not our therapy could be approved. She said that at the stage we are at this moment, the EMA could provide general guidance on Advanced Therapy Medicinal Products (ATMPs) because we don’t have in vivo results yet.
Conclusions: If we had in vivo results, we could get a recommendation of the EMA so that the EuCo approved our therapy. At the moment we can obtain advice about the ATMPs.

It's crucial to understand the risks involved, especially when handling GMOs and biological materials
Aim: Judit Regidor, Jose Ramon Gumiel and Judit Monlleó work at the Occupational health and safety unit, and Environment unit of OSSMA. OSSMA is the Security, Health and Environment Office of the University of Barcelona, and it helps to prevent laboral risks and damages to the environment.
Contribution: They highlighted the necessity of strict safety protocols when handling GMOs and biological materials. They emphasised the importance of using biosecurity cabinets, nitrile gloves, and appropriate disinfection methods to prevent contamination and exposure. The team also discussed the need for spill kits for both chemical and biological incidents and stressed regulatory compliance regarding the transport and disposal of GMOs to prevent accidental release.
Conclusions: It is fundamental that we keep in mind all the safety protocols and we use all the appropriate methods for dealing with GMOs.

It is essential to precisely define the regulatory category of the treatment
Aim: Jesús Corredor is head of Market Access at AstraZeneca, a pharmaceutical company; we talked to him in order to know more about the regulatory landscape and production process related to our therapy.
Contribution: Jesús highlighted the importance of understanding the regulatory category of a treatment, as it defines the requirements and costs for approval. He explained that cell-based therapies, like CAR-T, are classified as medicines and must meet national and European regulations. He also mentioned exploring hospital exemptions for direct production. Aligning with regulations early is key to avoiding delays and ensuring smooth clinical trials and commercialization.
Conclusions: Identifying the right regulatory framework is crucial for compliance and speeding up approval. Exploring hospital exemptions and understanding European regulations can help reduce delays and costs.

There are a lot of biosecurity controls for genetically modified cells
Aim:Aristides is doing post-doctoral research in new advanced therapies and rare genetic diseases at the Institut de Recerca Sant Joan de Déu. We contacted him to understand how to implement CRISPR modifications to our therapeutic product.
Contribution: Arístides pointed out that while CRISPR technology is permitted for academic use, its application in treatments involves more complex regulatory considerations, including patent issues and intellectual property rights. He emphasised the importance of adhering to the European Medicines Agency (EMA) guidelines to ensure that the modified cell lines meet safety and efficacy standards before clinical use. This regulatory insight is vital for navigating the path from research to application.
Conclusions:He emphasised that CRISPR raises complex regulatory issues, particularly regarding patents and intellectual property; he also noted the necessity of following EMA guidelines to ensure modified cell lines meet safety and efficacy standards.

We seek FDA approval; but the price must be approved by the EMA
Aim: Marc is a neurologist of the Stroke Unit of Vall d’Hebron, he has also worked in stroke research and has been awarded by the Spanish Neurology Society.
Contribution: Marc discussed the critical need for regulatory approval from bodies like the FDA and EMA, emphasising the importance of establishing a compelling narrative through preclinical studies to demonstrate safety and viability. His insights into the regulatory landscape are essential for navigating the complexities of introducing new therapies within legal frameworks.
Conclusions: Helped us gain sight about regulatory approvals for new therapies.

In your case, you do not need ‘cell storage’, but rather a ‘manufactured drug storage
Aim: Joaquin Antonio Delgadillo is the head of regulatory affairs at the Catalan Blood and Tissue Bank, a public entity responsible for ensuring the supply of blood and tissue in Catalonia. We reached out to him for his expertise in regulation law and managing cell banks.
Contribution: Joaquin discusses the potential of their therapy to be applied to a larger patient population, emphasising the importance of scaling production effectively. He notes that for the therapy to be implemented successfully, it is essential to maintain cost efficiency while ensuring that the treatment can reach as many patients as possible. This scalability is key for maximising the impact of their innovative stroke therapy.
Conclusions: His insights highlight the need for effective scaling of production and cost efficiency to ensure the successful implementation of the therapy.

Setting up your own clean room would probably take about a year
Aim: Sol Ruiz is a representative of the Spanish Agency of Medicines and Medical Devices (AEMPS), which ensures the security, quality and effectiveness of medications in Spain.
Contribution: Sol highlighted that to ensure the commercial viability of a treatment, it is essential to have suitable production facilities. She recommended collaborating with certified facilities that already have a clean room, instead of building your own, which would take significant time and resources. She also mentioned that scalability and cost control are critical aspects that must be clearly defined before moving forward with the regulatory and clinical process.
Conclusions: We should collaborate with facilities that are already authorised for manufacturing products in controlled environments for the purpose of reducing costs and accelerating the scale-up process.

If the patient population is large, inefficiencies in the processes are amplified, which could significantly increase costs
Aim: Jesús Corredor is head of Market Access at AstraZeneca, a pharmaceutical company; we talked to him in order to know more about the regulatory landscape and production process related to our therapy.
Contribution: Jesús stressed the importance of minimising inefficiencies in production and administration to manage costs as patient populations grow. He highlighted the role of certified hospital facilities and suggested leveraging existing partnerships to reduce manufacturing and regulatory costs. Collaborating with hospitals that already have certified facilities, rather than building new ones, can save significant time and resources, ensuring smoother production scalability.
Conclusions: Due to the growth of the patient populations, we should reduce costs; one way of doing so could be contemplating existing partnerships and collaborating with hospitals with certified facilities.

Europe’s medicine regulation was born because of tragedies, such as focobella
Aim: Joaquin Antonio Delgadillo is the head of regulatory affairs at the Catalan Blood and Tissue Bank, a public entity responsible for ensuring the supply of blood and tissue in Catalonia. We reached out to him for his expertise in regulation law and managing cell banks.
Contribution: We understood that the cost of maintaining a cell bank can depend on many variables, and the large but necessary process of creating an advanced therapy. We talked about how your therapy must be approved in order to store it, however, there is the alternative of producing the cells when we need them; all of this is determined by the production time and the product’s stability.
Conclusions: We have a range of options depending on our needs, but reducing cell lines will be cheaper.

For banking with subsequent clinical application, serum-free media are used, and they have a reduced concentration of DMSO.
Aim: Manuel Reina is an expert in cell preservation and handling, with a focus on improving safety measures and optimising the process of cell transfection for clinical applications.
Contribution: Manuel explained two main options for storing cells: vitrification, a cheaper method that can maintain cells at -80°C for up to 10 years, or slow freezing, which is more expensive. He also discussed FDA-approved freezing mediums that are serum-free and have reduced DMSO concentrations, ensuring cell viability post-thawing.
Conclusions: Vitrification is a cost-effective method for long-term cell storage in clinical settings.

For biological spills, we use absorbent materials like sepiolite and ensure proper disinfection
Aim: Judit Regidor, Jose Ramon Gumiel and Judit Monlleó work at the Occupational health and safety unit, and Environment unit of OSSMA. OSSMA is the Security, Health and Environment Office of the University of Barcelona, and it helps to prevent laboral risks and damages to the environment.
Contribution: The representatives explained the safety measures in place for both chemical and biological spills, emphasising the need for specific materials and protocols. They discussed the importance of training personnel in best practices to effectively mitigate risks associated with handling biological materials. Their insights reflect a commitment to maintaining a safe laboratory environment for everyone involved.
Conclusions: We understood the proper protocols for handling and storage of biological materials.

Hospitals already have the infrastructure you need
Aim: Manuel Reina is an expert in cell preservation and handling, with a focus on improving safety measures and optimising the process of cell transfection for clinical applications.
Contribution: Manuel discussed the importance of having a stable cell line with regulated expression for effective therapeutic outcomes. He emphasised the need to quantify doses accurately when working with hundreds of millions of cells and suggested methods for minimising risks associated with freezing and thawing transfected cells. His recommendations included using specific freezing media approved by the FDA and ensuring that cells are maintained at optimal temperatures for viability.
Conclusions: We have to find a way to optimise transportation in order to ensure a correct administration and cell viability.

You can study other non-invasive ways to access directly to the brain
Aim: Albert is Team Leader of a research group focused on Huntington’s disease. He has already worked with BDNF which is why we wanted to talk with him about its limitations.
Contribution: Albert talked to us about other non-invasive ways to administer our therapy to the patient. He introduced us to the retroorbital injection where the optic nerve is punctured, however, this technique has only been tested on mice. He also explained to us the intranasal injection, he told us there is olfactory neuroepithelium that can reach the CNS.
Conclusions: Some possible non-invasive ways to apply our product could be the retroorbital and intranasal injections.

Nowadays, intracranial administration is a minimally invasive intervention
Aim: Xabi Urra is a neurologist and researcher focused on stroke treatment and neuroprotection. He works at Hospital Clínic in Barcelona and has made significant contributions to stroke management and immune response studies.
Contribution: When asked about our therapy’s administration, Xabi told us that the procedure is fairly similar to a “minimally invasive surgery”; it is an injection with a small and not greasy catheter that avoids causing damage to the healthy tissue. The post-operatory is simple, with an exorbitant security: less than 2% of the patients are left with serious sequels.
Conclusions: Our way of administering our therapy is very secure and has a simple post-operatory.

There are secondary transportation services to take stroke patients to the hospital, such as collective health transport
Aim: Toni Garcia is a doctor based in Agramunt, a rural town near Lleida. We reached out to him to gain insight into the challenges of healthcare in smaller hospitals, which often have fewer resources compared to the larger facilities in Barcelona.
Contribution: In rural settings like Agramunt, secondary health transportation services are crucial for stroke patients, especially for follow-up visits and rehabilitation. These services include collective transport and ambulances, helping to overcome the distance to hospitals. However, the frequency of these trips and reliance on external services add complexity to patient care, especially for the elderly.
Conclusions:Efficient transportation is essential for ensuring that stroke patients in rural areas can receive timely rehabilitation and follow-up care.

You will have to check if you need to perform more than one administration during the preclinical phase
Aim: Marc is the Head of the Stroke Research team at the Hospital of Vall d’Hebron Institute, he has also worked in stroke research and has been awarded by the Spanish Neurology Society.
Contribution: Marc Ribó emphasised the critical importance of careful patient selection and compatibility testing in stroke treatment administration, even though the cells are universalised. He underscored the possibility of needing more than one administration, keeping in mind that, ideally, it would be just after the stroke. He highlighted the necessity of determining the ideal administration route, advocating for intra-arterial methods while acknowledging logistical challenges with an intrathecal injection.
Conclusions: We must consider patient selection even with universal cells, and we should also contemplate that it might take more than one administration. Regarding the route of administration, he advocated for the intra-arterial injection.

Clinical assays are very expensive and usually it is difficult to involve powerful companies
Aim:Francisco Moniche is an award-winning neurologist specialising in stroke treatment and clinical research. He is Head of the Stroke Unit at the Hospital Virgen del Rocío in Seville and has contributed significantly to studies on stroke therapy.
Contribution: He explained to us the different ways to apply our product to patients and its advantages and drawbacks: an intraarterial injection is a promising procedure but it requires an arteriogram first, and an intravenous option isn’t as localised as the intracerebral injection, but it also carries fewer risks.
Conclusions: Our best options are intracerebral and intravenous injections.

If there are no hemodynamic complications, go ahead. We start with the treatments as soon as possible
Aim: Míriam has worked at Hospital Arnau de Lleida for 30 years helping with rehabilitation. Nowadays she helps the most affected patients on their first days.
Contribution: When asked about our therapy’s route of administration, she said that as long as there aren’t hemodynamic complications, we should proceed. She believes in starting the treatment as soon as possible, even if the patient is slightly immobilised. Míriam noted that recovery and cognitive therapy wouldn’t be excessively impacted, therefore an intracranial injection is feasible.
Conclusions: If there are no hemodynamic complications recovery and cognitive therapy won’t be nearly impacted. She advocates for the intracranial injection, and thinks we should administer it as soon as possible.

The main problem I see is accessibility to some parts of the brain
Aim: We wanted to ask stroke survivors about the administration of our product, because in the end it’s them who decide whether or not to use it.
Contribution: The intracerebral injection has raised concerns because it is more invasive. However, it has been approved, although some patients have warned that complications could arise depending on the specific region of the brain being treated. Despite these concerns, many relatives told us they would have accepted any chance of hope at that critical moment. As some put it, their loved ones "were already gone."
Conclusions: There is some reluctance but any possibility of improvement would have been welcomed and tried.

“I would like to know the cause [of the stroke]”
Aim: Inés’s daughter suffered from a hemorrhagic stroke when she was only 7 years old. Even though the sequels are under control, she has episodes of epilepsy and has lost peripheral vision.
Contribution: Inés was disappointed about the immediate treatment because as the child was vomiting she was first diagnosed with gastroenteritis. It was when they joined private health that she was transferred to Sant Joan de Déu, Catalonia’s best children’s hospital. They would like to know the origin of it, but doctors told them it’s just bad luck. Inés thinks it’s important to research new treatments, and they would have tried our therapy if it had been approved, because they were always open to join clinical trials.
Conclusions: A delayed diagnosis can cause a lot of damage.

It seems like he’s self conscious about the illness, but he doesn’t want to accept it
Aim: Marta’s husband had an ischaemic stroke in the frontal part of his brain. He was left with aphasia, 77% of disability and a level 3 degree of dependency.
Contribution: Marta’s husband lived a healthy life before he suffered from a stroke: although he was retired he walked from 15.000 to 20.000 steps every day, and along with his wife, he was very active. For this reason they have no idea of the cause of the stroke, and Marta said that if she had a million dollars she would spend it on stroke prevention. When asked about our therapy, she said she would have probably tried it, as long as she could get a little of her husband back.
Conclusions: A stroke can happen unexpectedly without visible risk factors.

The doctor and I [her husband] used to say that she was a ‘little miracle’
Aim: Elena suffered from an aneurysm that caused a hemorrhagic stroke with many complications that affected the frontal lobe of her brain, and therefore she often loses track of time. She also has epilepsy and a slight imbalance.
Contribution: The time at the hospital was very hard for Marc and his wife, she had the stroke just 24h before the surgery for the aneurysm. She then had a series of spills and internal hematomes; lastly she got a facial herpes which paralysed half her face, and the doctors thought it was another stroke. They told us they would have tried our therapy if it weren’t for all the trauma regarding the uncertainty and worsening of her aneurysm.
Conclusions: In a complicated diagnosis, people tend to be more afraid to try new things.

There is a strong shock because the person you were talking to last night is now laying on a hospital bed
Aim: Enola’s husband suffered an ischaemic stroke while sleeping 13 years ago that affected the right part of the brain, the Broca’s area and the language region. He has made a great recovery considering where he began from.
Contribution: As other interviewed patients, Enola’s husband had no visible risk factors before the stroke and was mentally very active, although he did suffer an emotional shock a month before the incident. They aren’t content with the way it was handled at the hospital because the doctors thought the stroke happened more than 5 hours before arriving at the hospital, so they didn’t try to eliminate the clot in order to avoid a blood spill. However, the family would have liked to be consulted about whether or not to take that risk.
Conclusions: Communication with the family is key in stressful moments to help cope with the situation.

I didn’t give it much importance, I thought my hand had gone numb
Aim: Grau suffered from two minor strokes and a slightly major one, that made him go to a hospital. He barely has any sequels, just a small tingling on his hands and face.
Contribution: While working, Grau noticed a slight tingling on his hand but didn’t think much of it; a week later the tingling appeared again, this time on his face too. A month later, the same thing happened but this time it was heavier, which eventually made him go to a hospital; then they diagnosed the three strokes and told him to go to rehabilitation. When asked about our therapy, he said that if he had been more affected by the stroke, he would have tried it, weighing the advantages and drawbacks.
Conclusions: Not all strokes hurt, and some may even go unnoticed.

I felt helpless in the waiting room
Aim: Jordi suffered from an ischaemic stroke that left him with 66% of disability. However, he can now walk with difficulties and has retained full cognitive function.
Contribution: Jordi woke up with a feeling of numbness on the left part of his body, he couldn’t get up and noticed a strange headache, but didn’t lose consciousness. His wife, a doctor, diagnosed him with a heart attack but once he got to the Hospital de Barcelona the doctors told him it was a stroke and transferred him to the Hospital Clínic de Barcelona. When asked about our therapy, he said he would have tried it, because “why not?”.
Conclusions:Strokes can present a wide range of symptoms, some similar to a heart attack.

My wife got scared and called an ambulance
Aim: Gerard suffered an ischaemic stroke after having some of its symptoms earlier that day. It affected his cerebellum (balance, coordination…) but he is now recovered.
Contribution:Gerard felt some stroke symptoms in the afternoon and went to hospital at noon, thanks to his wife who called an ambulance. He had been vomiting, had a blurred vision and couldn’t speak well; the doctors immediately diagnosed him with a stroke, and just an hour later he was already admitted at the Hospital Universitari Bellvitge. At recovery, he met a man with a similar situation but they treated him four hours after the crisis; Gerard recovered, but this man had deeper sequels. Gerard said he would try our therapy if it was approved, although we would have trouble convincing the family and the first patients.
Conclusions: We need to learn to rapidly identify stroke symptoms because time really is brain.

[The doctors] had very little tact
Aim: Miguel suffered from an ischaemic stroke that paralysed the right part of his body and caused him total aphasia. After 20 years of rehabilitation he can now walk with difficulty, has partial aphasia and has a bad hand.
Contribution: Miguel started convulsing and as they were wondering whether he would survive the doctors asked them about organ donation, which the family felt as insensitive. They say the first day was devastating, mainly because of the uncertainty and the sudden realisation that the stroke was going to mark a turning point. When asked about our therapy, they would have accepted it without doubt, and Maria and Clàudia agree that it helps the fact that our expanded therapeutic window gives the relatives time to process the whole shock.
Conclusions: We must keep in mind the relative’s feelings and respect the time they need to deal with the trauma a stroke involves.

When you survive a stroke, it doesn’t change your life expectancy; it changes how you’ll live it
Aim: Fundació Ictus aims to give better attention to stroke survivors, their friends and their families. They focus mainly on rehab and prevention.
Contribution: We gained insight into the whole process related to a stroke: After the first alert either by calling 112 (Catalonia’s number of emergency services) or the hospital, the “stroke code” is activated. Then a first CT scan is performed to determine if you are having a hemorrhagic or an ischaemic stroke and you are transferred to a Catalan stroke unit to receive the appropriate treatment.
Conclusions: We learned about the Catalan’s health stroke protocol.

There are no specific treatments for strokes
Aim: Xabi Urra is a neurologist and researcher focused on stroke treatment and neuroprotection. He works at Hospital Clínic in Barcelona and has made significant contributions to stroke management and immune response studies.
Contribution:Xabi Urra stresses the importance of facilitating early discharge for stroke patients to home or rehabilitation centres. He highlights the need for coordinated care among medical professionals to support effective recovery and improve patients' chances of regaining independence and quality of life.
Conclusions: Effective stroke treatment relies on timely intervention and teamwork among healthcare professionals. Prioritising patient support and rehabilitation significantly boosts recovery outcomes.

If you give peace to the family, you give peace to the patient.
Aim: Míriam has worked at Hospital Arnau de Lleida for 30 years helping with rehabilitation. Nowadays she helps the most affected patients on their first days.
Contribution: Míriam discussed the significant impact of family dynamics on patient recovery, stressing that family education and involvement are key to a patient’s emotional well-being. She pointed out that about 50-60% of recovery depends on patient motivation, with family support accounting for another 20%. This highlights the necessity for comprehensive support systems that include both patients and their families.
Conclusions: A patient's emotional well-being and family support are critical to stroke recovery.

The main need for stroke patients is to reduce their disability
Aim: Marc is the Head of the Stroke Research team at the Hospital of Vall d’Hebron Institute, he has also worked in stroke research and has been awarded by the Spanish Neurology Society.
Contribution: Marc pointed out that a significant portion of stroke patients live with substantial disabilities, underscoring the urgent need for effective treatments. He noted that patients are generally open to therapies that promise improvement, especially if demonstrated through clinical trials. This perspective is vital for tailoring approaches that prioritise patient needs and outcomes in stroke care.
Conclusions:We must focus on reducing disability and improving patient outcomes.

I like to say it’s 28,000 euros per patient, not 40 billion in total. It’s easier for the general public to understand.
Aim: Pere Cardona is the director of the Neurovascular program and the Stroke Unit at Hospital Universitari de Bellvitge (HUB).
Contribution: Dr. Cardona provided valuable insights into the current state of stroke treatment, emphasising the need for new therapies that can work alongside established methods. He discussed the challenges faced in clinical trials and the importance of using advanced imaging software to select appropriate patients for treatment.
Conclusions: There is a need for new therapies that can work alongside established methods.

Patients are very concerned about premature death and quality of life
Aim: Pilar Azcárrega is the General Director of Public Health, Quality and Innovation and Cristina Guijarro is a medical inspector; they both work at the Spanish Ministry of Health, which ensures equity and quality health services in Spain.
Contribution: This interview highlighted the critical aspects of patient care, particularly the emphasis on preventing premature death and enhancing quality of life for stroke survivors. It underscored the necessity for healthcare strategies that prioritise patient outcomes and experiences, indicating a gap in current treatment methodologies that need to be filled. Pilar and Cristina mentioned that the Ministry's goal is to ensure the broadest possible access to the best healthcare. While the system may not be ready now, they believe that within 10 years, Spain's healthcare system could be prepared to adopt our therapy
Conclusions: Improving the quality of life and preventing premature death are top priorities for stroke patients. There is a need for healthcare strategies that better address these concerns, and Spain may be ready to adopt our product in 10 years.

[Your therapy] addresses a priority need for stroke patients.
Aim: Ariadna Mas is the General Deputy Director of Health Planning and Dr. Sònia Abilleira is the Director for the Strategic Plan for Cerebrovascular Diseases. They both work at CatSalut, the Catalan Service of Health.
Contribution: The conversation emphasises that the therapy directly targets significant disabilities resulting from strokes, which is a major concern for both patients and healthcare providers. By focusing on these needs, the therapy aims to improve the quality of life for survivors, addressing an urgent medical gap in stroke care.
Conclusions: Targeting disability is crucial for enhancing patients’ recovery.

She has always been the ‘ill kid,’ but she has fought against it
Aim: Inés’ daughter suffered from a hemorrhagic stroke when she was only 7 years old. Even though the sequels are under control, she has episodes of epilepsy and has lost peripheral vision.
Contribution:Inés’ daughter has to do physiotherapy because she has a stiff neck due to the vision loss, she also has to deal with epilepsy, although the crises are now less frequent. Unfortunately she has faced the stigma of being the “ill kid” at school, because she is also pharmacoresistant to epilepsy crises; despite all she has always fought against this perception and never doubted herself.
Conclusions: She can now live a normal life while being cautious, but she did notice the stigma associated with stroke.

I need to get my husband back. I need my husband
Aim: Marta’s husband had an ischaemic stroke in the frontal part of his brain and he has aphasia, 77% of disability and a level 3 degree of dependency.
Contribution: There hasn’t been any kind of neurological tracking of Marta’s husband after the stroke. They tried going to a speech therapist and a physiotherapist but didn’t like how they talked to him –like he was a child. He now lives in a state of reclusion, only leaves the house to walk his daughter’s dog and take out the trash, and only walks from the TV to the bed and vice-versa. Marta is devastated about how much the stroke has changed her husband and she can barely go out because he gets in a really bad mood.
Conclusions: The stroke has taken away most of Marta’s husband’s life, with nearly no recovery prognosis from the beginning.

My family has always been by my side
Aim: Elena suffered from an aneurysm resulting from hemorrhagic stroke with many complications that affected the frontal lobe of her brain, and therefore she often loses track of time. She also has epilepsy and a slight imbalance.
Contribution: Elena attended the Guttmann Institute of Neurorehabilitation, and she was taught how to play “HayDay”, a farm game that trained her to do sequential actions. People around her have been amazed by her rapid recovery, and have always supported her with love. She sometimes has an imbalance when playing with her grandson, so now she is doing taichi to harmonise her body’s movements again.
Conclusions: There are unexpected ways to recover one’s functions.

Recovery depends on the family environment
Aim: Enola’s husband suffered an ischaemic stroke while sleeping 13 years ago that affected the right part of the brain, the Broca’s area and the language. He has made a great recovery considering where he began from.
Contribution: Enola’s husband also attended the Guttmann Institute of Neurorehabilitation, and made a great recovery there, however, the centre was “like a bubble” and when he left he faced the reality shock of living with his condition. Enola highlights the importance of a sense of humour and of sincerity. She also claims that the fact that he was intellectually active really helped with the recovery; despite this, the road has been extremely hard: learning basic things from scratch, the slowness of the process… The patient’s family tried to give him the maximum independence they could, they remarked the importance of him regaining his decency.
Conclusions: The family, along with the lifestyle previous to the stroke are some of the essential pillars to a good recovery.

I was able to keep working until I retired
Aim: Grau suffered from two minor strokes and a slightly major one, that made him go to a hospital. He barely has any sequels, just a small tingling on his hands and face.
Contribution: Grau sequels were very subtle, he was told to go to rehabilitation but they told him he was in great shape and it wasn’t necessary. The tingling has remained on his hand and face, but he says he got used to it and it doesn’t bother him anymore, he keeps a healthy lifestyle, as doctors recommended. Everyone around him was surprised about his state and told him it didn’t look like he suffered from three strokes.
Conclusions: Sequels can vary a lot depending on the severity of the stroke.

I could not share the mountains with them [my grandchildren]
Aim: Jordi suffered from an ischaemic stroke that left him with 66% of disability. However, he can now walk with difficulties and has retained full cognitive function.
Contribution: Jordi hasn’t recovered the full function of the left part of his body, he walks with difficulties and his hand is a bit stunted; Jordi had been an avid skier. He used to watch people his age skiing with their children and grandchildren and dreamed of doing the same with his family, but the stroke made that dream come to a halt. He also is mentally exhausted every time he leaves his home, which makes it a lot more difficult.
Conclusions: For some people, mental sequels are just as debilitating as physical ones.

I now miss more buses than beforee
Aim: Gerard suffered an ischaemic stroke after having some of its symptoms earlier that day. It affected his cerebellum (balance, coordination…) but he is now recovered.
Contribution: Gerard recovered at the Guttmann Institute of Neurorehabilitation, where he met some celebrities that had also suffered from a stroke; he had no trouble speaking or seeing, but his balance and coordination were the problem. That’s why he was asked to paint mandalas, hang clothes with clothespins… He has the right part of his body more affected, he can’t run although he is able to drive and walk. He has gone back to work but he says long meetings exhaust him more than before, continuous noises annoy him too.
Conclusions: Recovery can bring back a normal life to some patients.

When you speak [to him] it’s devastating to see his blank stare
Aim: Miguel suffered from an ischaemic stroke that paralysed the right part of his body and caused him total aphasia. After 20 years of rehabilitation he can now walk with difficulty, has partial aphasia and has a bad hand.
Contribution: Miguel wandered through different rehabilitation centres, and they have seen how important it is to have a supportive environment. 20 years later, he still goes to the Guttmann Institute of Neurorehabilitation, a truly uncommon situation, as not everyone can afford private treatment. In fact, they talked about how after three months, the public system “kicks you out” and “leaves you on your own”. They are grateful for all his friends who have helped them enormously, and appreciate how other patients or physiotherapists have never treated him as a child.
Conclusions: Not everyone can afford 20 years of private rehabilitation, but it really makes a difference.

We do not need to talk about disability, we should talk about new capacities
Aim: Fundació Ictus aims to give better attention to stroke survivors, their friends and their families. They focus mainly on rehab and prevention.
Contribution: This meeting highlighted the often-overlooked challenges stroke patients face after their hospital stay, including shame, stigma, vulnerability, and the complex process of physical, cognitive, and emotional recovery. However, there is hope, with initiatives like the VALUE and HARMONICS and the innovative ABRIC system working to support patients' post-stroke lives.
Conclusions: There is an overlooked stigma towards stroke survivors.

The neurons that are dead are dead. The latent ones are the ones that could 'revive
Aim: Míriam has worked at Hospital Arnau de Lleida for 30 years helping with rehabilitation. Nowadays she helps the most affected patients on their first days.
Contribution: This interview introduced us to Penfield's Homunculus, a key brain area to consider due to its significant role in functional recovery. She also underscored the importance of timely rehabilitation, particularly within the first 24 hours post-stroke. Míriam highlighted that engaging patients early in their recovery process can drastically enhance their functional outcomes, suggesting that the sooner rehabilitation begins, the better the chances for recovery. She also pointed out the role of emotional support in recovery, both for patients and their families.
Conclusions: Early rehabilitation is crucial for optimising recovery in stroke patients, as it increases the chances of neuronal revival and functional improvement.

The combination of neuroprotective agents and regeneration is crucial for recovery post-stroke.
Aim: Pere Cardona is the director of the Neurovascular program and Stroke Unit of the Hospital Universitari de Bellvitge (HUB).
Contribution: The conversation revealed Cardona's perspective on the role of neuroprotection and regeneration in improving recovery outcomes for stroke patients. He expressed optimism about the therapy’s potential to enhance recovery processes, while also acknowledging the existing limitations in research and application. His insights could guide future strategies to incorporate recovery-focused elements into the therapeutic approach.
Conclusions: The goal is to enhance recovery through neuroprotection and regeneration.

The idea is great because if we can achieve regeneration, it would be revolutionary
Aim: Toni Garcia is a doctor based in Agramunt, a rural town near Lleida. We reached out to him to gain insight into the challenges of healthcare in smaller hospitals, which often have fewer resources compared to the larger facilities in Barcelona.
Contribution: Toni expressed strong support for regenerative therapies, noting that, in most cases, stroke patients are left with some form of damage even after clot removal. He believes that therapies aimed at regenerating the damaged brain tissue would be revolutionary and greatly improve outcomes for stroke patients, who currently face limited recovery options.
Conclusions: Regenerative therapies could transform stroke recovery by addressing long-term damage that current treatments can't repair.

Small movements are essential for neurorehabilitation
Aim:Héctor López Carral is an expert in rehabilitation systems that track body movements, particularly focused on improving mobility in stroke patients through interactive gaming systems.
Contribution: Héctor emphasised the importance of small, precise movements in neurorehabilitation and highlighted the use of 3D body tracking systems like the ones developed by Eodyne for upper limb recovery. He suggested that games tailored for stroke rehabilitation need body movement tracking beyond just hand gestures, and mentioned the potential to adapt existing game setups for clinical use.
Conclusions:Tracking precise movements in 3D is crucial for effective neurorehabilitation therapies.

The goal is for the patient to leave the hospital quickly, either home or to a recovery centre
Aim: Xabi Urra is a neurologist and researcher focused on stroke treatment and neuroprotection. He works at Hospital Clínic in Barcelona and has made significant contributions to stroke management and immune response studies.
Contribution: He explained the structured approach in hospitals involving a multidisciplinary team to ensure optimal patient outcomes, from initial treatment to recovery.
Conclusions: A coordinated care approach is essential for improving recovery rates in stroke patients.

A high percentage of patients do not recover functionality even after fibrinolysis
Aim:María is Head of the Stroke Unit of the Hospital La Paz, from Madrid. This unit has been operative for more than 20 years and has attended more than 1.200 patients. Contribution: She addressed the limitations of existing treatments, stating that her therapy could serve as an additional option for patients who have or have not received standard treatments. The focus was on improving patient outcomes through innovative approaches.
Conclusions:Enhanced recovery strategies are essential to improve functional outcomes for stroke patients.

There is an improvement in the response time to strokes
Aim: Pilar Azcárrega is the General Director of Public Health, Quality and Innovation and Cristina Guijarro is a medical inspector; they both work at the Spanish Ministry of Health, which ensures equity and quality health services in Spain.
Contribution: The conversation revealed that improvements in response times are critical for reducing the long-term effects of strokes. It also pointed out the urgent need for innovative treatments to complement these advancements. Highlighting this relationship between timely intervention and recovery can guide future research and healthcare practices.
Conclusions: Improved response times are critical for better stroke recovery outcomes. Further innovation in treatment is needed to complement these advancements in stroke management.

Ageing-related pathologies should be a primary focus
Aim: Ariadna Mas is the General Deputy Director of Health Planning and Dr. Sònia Abilleire is the Director for the Strategic Plan for Cerebrovascular Diseases. They both work at CatSalut, the Catalan Service of Health.
Contribution: The discussion points to the importance of a holistic approach that addresses both stroke recovery and the underlying health issues associated with ageing. By integrating this therapy into a comprehensive care model, it aims to promote better health outcomes and a higher quality of life for older patients.
Conclusions: A comprehensive approach enhances recovery in ageing populations.