Periodic Reporting for period 1 - PLATFORMA (Peripheral Nervous System Tissue Engineering for Medical and Cosmetic Testing Applications) Reporting period: 2020-10-01 to 2021-09-30 Summary of the context and overall objectives of the project What is the problem being addressed?Advances in the treatment of many human health conditions depend on access to representative testing systems that allow researchers to quickly evaluate the potential of new drug therapies. In some fields, the options are limited and efforts to reduce the amount of animal testing used are also creating a strong need to find better solutions. In the field of research focused on Amyotrophic lateral sclerosis or ALS, a progressive nervous system disease that affects nerve cells in the brain and spinal cord, causing loss of muscle control, there are a distinct lack of model systems that are sufficiently representative of the human condition which is hindering the investigation and development of effective treatment options. Similarly in the field of cosmetic testing, previously very reliant on animal testing, better and better alternatives are needed to ensure that cosmetics are developed that reach the highest safety standards possible.Why is it important for society?The average incidence rate of ALS worldwide is about one in 50,000 people per year that equates to about 5,760 to 6,400 new diagnoses per year. According to some estimates, the number of cases of ALS in the world will increase from 222,801 in 2015 to 376,674 in 2040, representing an increase of 69%. The largest increase will be seen in Africa with 116%, followed by Asia with 81% and South America with 73%. ALS is fatal. The average life expectancy after diagnosis is two to five years, but some patients may live for years or even decades. (The famous physicist Stephen Hawking, for example, lived for more than 50 years after he was diagnosed.)Testing represents an important part of a cosmetic product registration process. Cosmetic products have to undergo all the required testing defined in the EU Cosmetics Regulation (EC) 1223/2009 in order to be compliant and more importantly, to prove they are safe for use under reasonably foreseeable conditions. What are the overall objectives?Skin Module will be a world first, a commercially available innervated human skin tissue model. It allows studies and testing of Peripheral Nervous System (PNS) responses to external stimuli in a physiologically relevant context. This module itself can be used to investigate activities of both dermal and nerve cells at the same time. When a stimulus is introduced on the skin layer, responses of skin cells and activities of sensory neurons (e.g. pain & itch) can be recorded simultaneously. The Applications of the Skin Module are as follows:• Peripheral neurotoxicity testing of cosmetics, pollutants, and transdermal delivery of new therapeutics, etc.• Development of wound healing assays and wound healing therapeutic strategies• Studies of interactions of human sensory neurons and dermal tissue Muscle Module is an innovative motor neuron-skeletal muscle tissue model. It allows non-invasive recordings of neuromuscular transmission in real time. The Applications of the Muscle Model are as follows: • Investigation of human neuromuscular junction formation and signal transmission upon administration of therapeutic agents. • Studies of muscular atrophies & motor neuron diseases with genetically engineered or patient derived cells. • Long-term monitoring and analysis of drug effects (toxicity and efficacy) with live 3D imaging and electro-physiological recordings. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far PLATFORMA has progressed broadly in line with the project schedule for P1 producing achievements across the full range of work packages and technologies planned. The key exploitable results (KERs) are centred upon the Skin-sensory neuron module and the Muscle-motor neuron module, and these have progressed to satisfactory technical levels, but with some challenges remaining. Beneficiaries have been active in developing the Communication plans of the project but, engagement with potential users has been hampered by COVID restrictions. Exploitation planning is progressing well, but challenges exist in ensuring that PLATFORMA technical solutions are commercially viable due to the high costs of cells.COMMUNICATION, DISSEMINATION and EXPLOITATION – A complete set of Deliverables encompassing all strands of the communication, dissemination and exploitation planning activities of the project have been achieved. The exploitation priorities of the project have been established, and the Freedom to Operate investigated and confirmation delivered that the partners are not currently aware of any restrictions to their plans. Competitor studies have taken place and market research undertaken to support the current assumptions around exploitation.There are currently no changes to the promised impacts of the project. Despite the delays and disruptions of the first period, the partners are holding to their belief that they will be able to achieve the promised impacts. However, this will require concerns over the commercial viability of the key Skin and Muscle modules to be addressed. There is currently a commercial risk of failure due to the high cost of the cell seeding density required. Cost down efforts are needed to reduce the cost per well to levels consistent with the prospects of securing market acceptance. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) The Skin Module will be championed by partner StratiCELL who have the belief in the concept, expertise, and relevant market knowledge to convert latent and explicit customer interest into downstream demand facilitated by the development of a skin-sensory assay for cosmetic and dermatologic testing. This project is offering disruptive testing services for early discovery and preclinical studies related to sensory skin disorders. The services will be used to screen efficacy of compounds but also topical formulations and finished products, enabling simultaneous testing of more compounds at lower cost and characterization of their mechanisms of action. This offer can also be customized to each customer’s case. The development of the Skin Module is aligned with the EU’s directive of eliminating animal models in cosmetics testing and reducing such use in drug development. The human Skin Module will be the world’s first commercially available in vitro innervated skin testing platform allowing StratiCELL to contribute in the development of a new market in cosmetic testing (sensorial-related wellbeing and sensitive skin) and offering highly relevant alternative testing offers for drug development (itch and pain).The Muscle Module will be championed by partner Axol who have identified an urgent market need amongst pharma-biotech companies for disease-relevant human neuro-muscular models in physiologically relevant 3D culture, as well as instant functional read-out on drug responses. Amyotrophic lateral sclerosis (ALS), a progressive fatal motor neuron degenerative disease affecting 222,801 patients in 2015 globally, is of particular interest amongst Axol’s current customers.