Challenge for advanced therapies Flashcards
(4 cards)
advanced therapies
Advanced therapies can be classified into 3 categories: 1. Somatic Cell Therapy 2. Gene Therapy 3. Tissue Engineering Example - Florida: Macular degeneration; treated with stem cells from adipose tissue caused blindness in both patients - Australia: patient died when they attempted to treat Dementia by injecting stem cells from adipose into the brain - Mesenchymal stem cells injected into spine of a patient with motor neuron disease, resulting in a tumour - Florida: was thought that the man had a stroke and was treated with stem cells to try and treat his baldness - Cancer researchers claiming T cell therapy could cause remission
injection and mode of action
What are We Injecting into Patients? Some problems are caused by irresponsible actions of companies, but there are also some genuine scientific issues. - Start off with cell population and test with an animal model for any possible clinical use in a lab, but does not produce clinical grade cells - Must then expand the cells and then undergo regulation and undergo new manufacturing processes to get to a viable product
Asterias Biotherapeutics Example Oligodendrocyte progenitor cells derived from hESC’s were transplanted into a patient to remyelinate and restore locomotion following a spinal cord injury which left him paralysed. The cells previously showed efficacy in animal models and its publication in a neuroscience journal implies that they knew what cells were being injected into the patient. A later paper published by them showed the problem that less than 50% of the cells were oligodendrocytes. Although over 50% of the cells were positive for NG2, they were uncertain which neural cells were being transplanted into the patient. Different preparations showed variable levels of therapeutic cell population to be injected.
What is the Mode of Action? Regulators do not insist on knowing how a drug works before clinical trials take place. E.g. antidepressant SSRIs were devised to block 5HT uptake and so 5HT concentration increases in the synapse to alleviate symptoms, but if this was the mode of action it would be very fast, rather than taking weeks to become effective. It is likely that they have a different mode of action. With advanced therapies, it is often true that the mode of action is not known
ossible modes of action: - Immunomodulation - Modulation of endogenous stem cells - Neurotrophic mechanisms How do we know that all the cell preparations are equally potent? Drug companies will know through potency assays but need to know the mode of action to design the assay. Regulators will allow stem cells to go through clinical trial process
the equipoise problem
Equipoise refers to a situation where there is genuine uncertainty among the clinical community about the comparative merits of different treatments. In other words, clinicians do not know if one treatment is more beneficial or harmful than another for the patient. Equipoise is a crucial ethical principle in the context of clinical trials. The idea is that, for a clinical trial to be ethically justified, there must be uncertainty about whether the experimental treatment is better than the standard treatment or placebo. If a treatment is already known to be more effective or harmful, then it would be unethical to conduct a trial that randomly assigns patients to receive the less effective or harmful treatment.
conflict of interest and informed consent
Conflict of interest in clinical trials arises when a company or organization funding or conducting a trial stands to benefit financially from the outcome of the research, which can potentially lead to biased results. For example, companies that produce a product or therapy may have less incentive to perform rigorous clinical trials if the product has not yet been proven effective or safe. This can lead to concerns about the reliability and transparency of the data.
An example of this is regenerative medicine, where some companies have charged patients up to $54,000 for therapies that have not been proven to be effective through well-conducted clinical trials. In such situations, informed consent is especially important. Patients must be fully informed about the potential risks, benefits, and the lack of scientific evidence supporting the therapy. Without proper informed consent, there is an ethical concern that patients may be exploited or misled.
To sum up: Conflict of interest can undermine the integrity of clinical trials, and informed consent is necessary to ensure that participants are aware of the trial’s status and risks, especially when dealing with unproven or experimental therapies.
