Genetic variability and potential effects on clinical trial outcomes: perspectives in Parkinson’s disease

[Farooqji]

Conclusions

Our data support the hypothesis that within genetically unmatched clinical trials, genetic heterogeneity could confound true therapeutic effects as expected. Clinical trials should undergo pretrial genetic adjustment or, at the minimum, post-trial adjustment and analysis for failed trials.

jmg.bmj.com/content/early/2...

[MarionP]

Same as all the different targeted cancer and immune-targeted treatments of late (anything whose generic name ends in "ib" and "mab" for example, which mean "immunoglobulin" and "monoclonal antibody") that target the disease through manipulating enzymes in the immune system of humans or the cancer cells....exactly the same thing. Cancer cells and normal human cells naturally generate their own unique gene mutations, which then become transmitted to their new daughter cells as your cells naturally reproduce (and even producing yet more mutations sometimes) and some of those mutations prevent the medication from doing its work.

Example: Keytruda that my daughter is on for her metastatic head&neck cancer. She had to have genetic testing to make sure that her cells and her cancer's cells didn't have such mutations before she could start on the medication, because they knew if she did then the medication would fail. Lots more examples, all you have to do is watch television commercials to see all the different arthritis examples, skin disease examples, Humira is another one, etc. Example of an entire class of such drugs: "kinase inhibitors" such as "tyrosine kinase inhibitors."

Makes prediction of treatment prospect and prognosis so much more complicated if the field is not prepared and able to do and appropriately interpret such tests on individual patients.

[pvw2]

Very true. For example, heavy metal poisoning is know to be a cause of PD. Mercury causes low thyroid. Studies found no correlation between PD and low thyroid. But, PD caused by mercury is estimated to be about 6%. Thus, one would expect low thyroid caused by mercury in PD patients to yield a correlation less than experimental error in the general PD population.