Techniques in disease

Description

Neurological and Psychiatric disorders Mind Map on Techniques in disease, created by Cher Bachar on 26/05/2013.
Cher Bachar
Mind Map by Cher Bachar, updated more than 1 year ago
Cher Bachar
Created by Cher Bachar over 11 years ago
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Resource summary

Techniques in disease
  1. Drug discovery
    1. Preclinical
      1. Clinical
        1. Drug failure
          1. Phase II
            1. Efficacy
              1. better animal models
            2. Translational research
              1. Develop disease biomarkers

                Annotations:

                • that indicate the disease- and the affects of interventions
                1. Applicable technologies (both humans and animals)- MRI, EEG
                  1. Use human tissue for lab exp
                    1. Better animal models
                    2. Approaches
                      1. Pathology to drug
                        1. novel drug
                        2. Reverse translation
                          1. improve current drug
                      2. Animal models
                        1. Categories
                          1. Developmental
                            1. Drug-induced
                              1. Lesion
                                1. Genetic
                                  1. transgenic manipulations
                                2. AD
                                  1. Disease mortifying- Develop drugs that interfer with disease mechanisms
                                    1. Sequence genes of familial mutations
                                      1. Animal models
                                        1. Transgenic overexpression of APP
                                          1. models familial mutations (only 10%)
                                            1. High levels of soluble Ab, Ab plaques, Memory deficits, elevated b-secretase
                                              1. Deficits in LTP (in some labs)- not representative
                                              2. No perfect model
                                                1. 95% AD cases are sporadic
                                                  1. elevated amyloid levels from early age point- not necessarily in AD
                                                    1. No NFT
                                                      1. No neurodegeneration
                                                        1. Cannot test neuroprotective (against neural loss) in most
                                                          1. See 4/5xFAD
                                                        2. APP + PS1 overexpression
                                                          1. APP + PS1 + tau
                                                            1. NFT
                                                              1. Ab diposition
                                                                1. No neuronal loss
                                                                2. 5xFAD
                                                                  1. aggressive Ab
                                                                    1. reduced synaptic staining
                                                                      1. neuronal loss
                                                                      2. 4xFAD
                                                                        1. aggressive Ab
                                                                          1. massive neuronal loss
                                                                          2. Transgenic rats
                                                                            1. cleverer than mice, but less well characterised
                                                                            2. Primates
                                                                              1. Biologically closer to humans
                                                                            3. Clinical trials
                                                                              1. require long clinical trials to see effects of progression
                                                                                1. improved cognitive tests
                                                                                  1. disease biomarkers- Ab
                                                                                    1. Non-invasive Ab measurements required
                                                                                      1. PET- metabolic changes
                                                                                      2. Blood/urnine- not good
                                                                                        1. CSF- better- invasove
                                                                                    2. Parkinsons
                                                                                      1. Schizophrenia
                                                                                        1. Depression
                                                                                          1. Epilepsy
                                                                                            1. SE

                                                                                              Annotations:

                                                                                              • a prolonged seizure (termed status epilepticus or SE) is induced by either electrical stimulation or a chemoconvulsant, leading to injury as the “initial precipitating event.” 
                                                                                              1. kainic acid

                                                                                                Annotations:

                                                                                                • chemconvulsant-induced SE models
                                                                                                1. pilocarpine

                                                                                                  Annotations:

                                                                                                  • chemconvulsant-induced SE models
                                                                                              2. Limitations
                                                                                                1. Construct validity
                                                                                                  1. Replicate the underlying biology
                                                                                                  2. Face validity
                                                                                                    1. Reflect the symptoms in man
                                                                                                    2. Predictive validity
                                                                                                      1. Predict treatments which will be effective in the human condition
                                                                                                      2. Clinically predictive
                                                                                                        1. pathophysiological-based animal models
                                                                                                          1. target pathways relevant for the disease
                                                                                                            1. Disease relevant end-points
                                                                                                              1. relevant biomarkers
                                                                                                              2. Strains
                                                                                                            2. General techniques
                                                                                                              1. Pharmacological
                                                                                                                1. On human/ animal model
                                                                                                                2. In-vivo/ in-vitro
                                                                                                                  1. animal model/ post-morten
                                                                                                                  2. Genetic
                                                                                                                    1. transgenic mice
                                                                                                                      1. GWAS
                                                                                                                        1. Microarrays- target genes
                                                                                                                          1. Familial screening
                                                                                                                          2. Correlation
                                                                                                                            1. Genes
                                                                                                                              1. Transmitter
                                                                                                                                1. Transcriptional factors/ proteins
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