Long-Term Toxicity of Immunosuppressive Therapy

Ruiz, Richard; Kirk, Allan D.

doi:10.1016/b978-1-4557-0268-8.00097-x

Cited by 21 publications

(17 citation statements)

References 66 publications

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“…Adverse drug reactions contribute to disability and the increasing need for care in older adults. For example, long-term use of immunosuppressants can lead to health ramifications like diabetes, infections, hypertension, and osteoporosis ( Lallana & Fadul, 2011 ; Ruiz & Kirk, 2015 ); this is concerning because various age-related illnesses such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and lupus are treated with immunosuppressants ( Lallana & Fadul, 2011 ). Furthermore, many of these age-related illnesses are an emotional burden to live with, which leads to hopelessness, isolation, and depression.…”

Section: Discussionmentioning

confidence: 99%

Is Use of Psychedelic Drugs a Risk or Protective Factor for Late-Life Cognitive Decline?

Fearn,

Bhattacharyya

2024

Gerontology and Geriatric Medicine

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Objectives: Common age-related health conditions can lead to poor mental health outcomes and deteriorate cognition. Additionally, commonly prescribed medications for various mental/physical health conditions may cause adverse reactions, especially among older adults. Psychedelic therapy has shown positive impacts on cognition and has been successful in treating various mental health problems without long-lasting adversities. The current study examines the association between psychedelic drug usage and cognitive functions in middle-aged and older adults. Methods: Data were from wave 3 (2013–2014) of the Midlife in the United States (MIDUS) study. We used multiple linear regression models examining associations between psychedelic usage and cognitive functions, controlling for covariates of sociodemographic and health factors. Results: We included 2,503 individuals ( Mage = 64 ± 11). After controlling for covariates, the finding revealed that psychedelic usage was independently associated with more favorable changes in executive function (β = .102, SE = 0.047, p = .031) and less depressive symptoms (β = −.090, SE = 0.021, p < .001). The same effect was not found for episodic memory (β = .039, SE = 0.066, p = .553). Discussion: Addressing the mental health implications of physical health conditions in older adults are vital for preventing neurocognitive deterioration, prolonging independence, and improving the quality of life. More longitudinal research is essential utilizing psychedelics as an alternative therapy examining late-life cognitive benefits.

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Section: Discussionmentioning

confidence: 99%

Is Use of Psychedelic Drugs a Risk or Protective Factor for Late-Life Cognitive Decline?

Fearn,

Bhattacharyya

2024

Gerontology and Geriatric Medicine

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“…21,23,50–54 Long term immunosuppression can increase the risk of infection and malignancy, as reported by clinical studies. 68–70 To enhance the beneficial effect of the grafts despite the limited survival rate, equipping the cells with cDNA of additional therapeutic substance that can be released from the graft is a viable approach.…”

Section: Discussionmentioning

confidence: 99%

“…21,23,[50][51][52][53][54] Long term immunosuppression can increase the risk of infection and malignancy, as reported by clinical studies. [68][69][70] To enhance the beneficial effect of the grafts despite the limited survival rate, equipping the cells with cDNA of additional therapeutic substance that can be released from the graft is a viable approach. Conopeptides, small peptides produced by marine cone snails, with unique affinity to various receptors within the CNS, have become a major focus for new drug development.…”

Section: Discussionmentioning

confidence: 99%

Analgesic effect of recombinant GABAergic precursors releasing ω-conotoxin MVIIA in a model of peripheral nerve injury in rats

2022

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Development of chronic pain has been attributed to dysfunctional GABA signaling in the spinal cord. Direct pharmacological interventions on GABA signaling are usually not very efficient and often accompanied by side effects due to the widespread distribution of GABA receptors in CNS. Transplantation of GABAergic neuronal cells may restore the inhibitory potential in the spinal cord. Grafted cells may also release additional analgesic peptides by means of genetic engineering to further enhance the benefits of this approach. Conopeptides are ideal candidates for recombinant expression using cell-based strategies. The omega-conopeptide MVIIA is in clinical use for severe pain marketed as FDA approved Prialt in the form of intrathecal injections. The goal of this study was to develop transplantable recombinant GABAergic cells releasing conopeptide MVIIA and to evaluate the analgesic effect of the grafts in a model of peripheral nerve injury-induced pain. We have engineered and characterized the GABAergic progenitors expressing MVIIA. Recombinant and nonrecombinant cells were intraspinally injected into animals after the nerve injury. Animals were tested weekly up to 12 weeks for the presence of hypersensitivity, followed by histochemical and biochemical analysis of the tissue. We observed beneficial effects of the grafted cells in reducing hypersensitivity in all grafted animals, especially potent in the recombinant group. The level of pain-related cytokines was reduced in the grafted animals and correlation between these pain markers and actual behavior was indicated. This study demonstrated the feasibility of recombinant cell transplantation in the management of chronic pain.

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“…For therapies targeting the brain or eye, temporary or local immunosuppression may be sufficient due to the relatively immune-privileged nature of these organs. However, life-long immunosuppression, which is associated with serious risks, including infections and cancer ( Ruiz and Kirk, 2015 ), remains an issue for other organs. This has led to the pursuit of autologous cell therapies in which hiPSCs are generated from the patient's own cells.…”

Section: Promising Advancements In Clinical Trialsmentioning

confidence: 99%

Clinical translation of pluripotent stem cell-based therapies: successes and challenges

Christiansen,

Kirkeby

2024

Development

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The translational stem cell research field has progressed immensely in the past decade. Development and refinement of differentiation protocols now allows the generation of a range of cell types, such as pancreatic β-cells and dopaminergic neurons, from human pluripotent stem cells (hPSCs) in an efficient and good manufacturing practice-compliant fashion. This has led to the initiation of several clinical trials using hPSC-derived cells to replace lost or dysfunctional cells, demonstrating evidence of both safety and efficacy. Here, we highlight successes from some of the hPSC-based trials reporting early signs of efficacy and discuss common challenges in clinical translation of cell therapies.

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Long-Term Toxicity of Immunosuppressive Therapy

Cited by 21 publications

References 66 publications

Is Use of Psychedelic Drugs a Risk or Protective Factor for Late-Life Cognitive Decline?

Is Use of Psychedelic Drugs a Risk or Protective Factor for Late-Life Cognitive Decline?

Analgesic effect of recombinant GABAergic precursors releasing ω-conotoxin MVIIA in a model of peripheral nerve injury in rats

Clinical translation of pluripotent stem cell-based therapies: successes and challenges

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