Autologous skin-derived neural precursor (SKN) cell therapy for canine cognitive dysfunction in older companion dogs (DOGS + CELLS trial)
An open-label Phase 1/2A veterinary trial at the University of Sydney, run over 2012-2020, treated six older companion dogs (aged 10-16 years) with a definitive diagnosis of canine cognitive dysfunction by MRI-guided microinjection of 250,000 autologous skin-derived neural precursor cells into both hippocampi. The primary endpoint was change in the CCDR scale at 3 months. Four of five evaluable dogs improved, three fell below the diagnostic threshold and two showed full syndromal reversal lasting up to 2 years; one dog had a surgical adverse event requiring euthanasia, and post-mortem hippocampal synaptic density was far above untreated dogs.
Record
| Design | single-arm trial |
|---|---|
| Status | completed |
| Setting | client owned |
| Intervention | Direct microinjection of autologous skin-derived neuroprecursors (SKNs) into the bilateral hippocampus using MRI-guided stereotaxis |
| Intervention class | cell or gene therapy |
| Comparator | None (open-label, no control arm); post-mortem histology compared with a brain bank (N = 12) of untreated aged dogs |
| Dose regimen | 250,000 autologous SKNs microinjected into the bilateral hippocampus |
| Duration | 3-month primary endpoint; clinical follow-up up to 2 years |
| Dogs | 6 |
| Population note | N = 8 recruited and N = 6 treated over 8 years; modified intention-to-treat analysis N = 5 |
| Age | aged 10-16 years |
| Other | older companion (community-dwelling) dogs with definitive diagnosis of Canine Cognitive Dysfunction (CCD); 2 female, 4 male |
| Primary outcome | Change in the Canine Cognitive Dysfunction Rating Scale (CCDR) from baseline to 3 months post treatment; safety assessed clinically |
| Result (as reported) | Four out-of-five dogs improved on the primary clinical CCDR endpoint, three fell below diagnostic threshold, and two underwent full syndromal reversal lasting up to 2 years (modified ITT paired T test = 3.06, df = 4, p = 0.038). At post mortem, hippocampal synaptic density was nine standard deviations above non-treated dogs. There was no impact on AD pathology or long-term safety signals; one patient had a surgical adverse event requiring euthanasia. |
| Lead organisation | University of Sydney |
| Start year | 2012 |
| End year | 2020 |
| Registrations | preclinicaltrials.eu PCTE0000169 |
| Tags | stem-cells, cell-therapy, cognition, ccd, hippocampus, surgery |
Notes: Borderline on framing: the authors present this as treatment of a canine Alzheimer dementia-like syndrome (CCD) in older dogs; included because CCD is the age-related cognitive decline of dogs. Single-arm, open-label, with no control arm; a companion aged-rat study is reported in the same paper. No funding statement located in the full text.
Sources and verbatim quotes
Autologous skin-derived neural precursor cell therapy reverses canine Alzheimer dementia-like syndrome in a proof of concept veterinary trial. (2022) PMID 35715872 (results)
Older companion dogs naturally develop a dementia-like syndrome with biological, clinical and therapeutic similarities to Alzheimer disease (AD).
A Phase 1/2A veterinary trial was conducted in N = 6 older companion dogs with definitive diagnosis of Canine Cognitive Dysfunction (CCD).
Treatment comprised direct microinjection of 250,000 autologous skin-derived neuroprecursors (SKNs) into the bilateral hippocampus using MRI-guided stereotaxis.
Safety was assessed clinically and efficacy using the validated Canine Cognitive Dysfunction Rating Scale (CCDR) at baseline and 3-month post treatment.
Intention to treat analysis imputed a single patient that had a surgical adverse event requiring euthanasia.
these were compared to a brain bank (N = 12) of untreated aged dogs with and without CCD
Four out-of-five dogs improved on the primary clinical CCDR endpoint, three fell below diagnostic threshold, and remarkably, two underwent full syndromal reversal lasting up to 2 years.
At post mortem, synaptic density in the hippocampus specifically was nine standard deviations above non-treated dogs, and intensity of new neurons also several fold higher.
There was no impact on AD pathology or long-term safety signals.
Autologous skin-derived neural precursor cell therapy reverses canine Alzheimer dementia-like syndrome in a proof of concept veterinary trial. (2022) PMID 35715872 (design)
This trial was approved by the University of Sydney Animal Ethics Committee, and because it spanned 8 years (2012–2020) the trial encompassed several protocol updates.
diagnosed in aged companion dogs (*N* = 6, 2 female, 4 male, aged 10–16 years
The trial was designed to PREPARE guidelines, including protocol registration PCTE0000169 on www.preclinicaltrial.eu
Over an 8-year period, we recruited *N* = 8 and treated *N* = 6 community-dwelling CCD dogs in the DOGS + CELLS trial (University of Sydney Animal Ethics Committee #2019/1612).
Modified intention-to-treat ITT analysis (*N* = 5) found a significant improvement on the trial’s primary endpoint
Modified ITT analysis: Paired *T* test = 3.06, *df* = 4, *p* = 0.038.
An open-label design was used in this veterinary trial for the same reason it is commonly employed in first-in-human cell therapy trials [45]: CCD is a progressive and terminal disorder and surgical delivery encompasses some risk; it was considered ethically inappropriate to employ an inert control arm.
Reproduce: canine_trial_search(trial_id="skn-cell-therapy-canine-cognitive-dysfunction-sydney-2022") in dog-geroscience-mcp; dataset canine-trial-registry.