Disclaimer: The examples shown below are for illustrative purposes ONLY. NINDS is not endorsing particular development plans or models, parameters, or cut-off values for any disease, modality, or stage of development. Therefore, NINDS expects Investigators to establish milestones appropriate for each development plan, but aligned with the recommendations indicated. Milestones and Examples
Hypothetical gene therapy development program for progressive thalamic neurodegenerative disorder
Specific Aim 1: Production of vector using cGMP process for IND-enabling toxicology studies
Milestone 1a: Produce rAAV8.CMV.GDGF vector for intracranial delivery to the thalamic ventroposteriolateral nucleus (VPL) of the allodynic mouse. 12 months.
Milestone 1b: Produce rAAV8.CMV.eGFP for intracranial delivery to the VPL of the rhesus macaque monkey. 9 months.
Milestone 2: Demonstrate persistence of expression of GDGF protein in the VPL of rhesus macaques treated with a transient immunosuppression regimen. 15 months.
Milestone 3: Completion of GLP safety and toxicology testing according to plan acceptable to the FDA.
Milestone 4: Submission of IND. 12 months.